Multilaboratory Assessment of Threshold versus Fold-Change Algorithms for Minimizing Analytical Variability in Multiplexed Pneumococcal IgG Measurements

Pneumococcal vaccination is frequently used to assess a patient''s humoral immune function. The comparison of pre- and postvaccination levels of antipneumococcal antibodies is widely held to be the gold standard for documenting a response. However, many of the published criteria for defining an adequate response are based on assays that are no longer widely available. We compared the clinical classification of patient response by multiplex pneumococcal assays currently performed at three large reference laboratories using a variety of published criteria for defining responses in adults. The classification of responders agreed for 79% of the patients when using a threshold-based algorithm compared to 57 to 96% of the patients when using various fold-change-based algorithms. The highest rate of discordance was seen when the most stringent criteria for response were used (4-fold increase postvaccination in 70% of serotypes). The discordant samples tended to show similar patterns of response across all three assays, with small variations in the final number of serotypes converting postvaccination. We conclude that the use of published cut points for documenting response to pneumococcal vaccination can be affected by interlaboratory differences in pneumococcal assays, particularly for algorithms that require large fold changes for a response to be documented. However, the overall patterns of response were similar in virtually all samples, regardless of the assay used.     

Psychosocial impact of testing (by linkage) for the BRCA1 breast cancer gene: An investigation of two families in the research setting

Data are reported on an investigation of the impact of genetic testing in two families with a >95% probability of linkage to the BRCA1 Breast/Ovarian cancer predispostion gene. Levels of psychological morbidity and cancer specific concerns in this highly selected group were not unusually high. At least half of the sample had no specific prior expectation regarding their gene carrier status. However, there was an indication that an unanticipated unfavourable genetic test result can cause subsequent psychological distress. Uptake of testing in this research sample was 41% overall and was higher (59%) in females. This is likely to have important resource implications if this level of uptake is found when genetic testing is extended outside such research cohorts.     

BoNT/A in the Urinary Bladder—More to the Story than Silencing of Cholinergic Nerves

Botulinum neurotoxin (BoNT/A) is an FDA and NICE approved second-line treatment for overactive bladder (OAB) in patients either not responsive or intolerant to anti-cholinergic drugs. BoNT/A acts to weaken muscle contraction by blocking release of the neurotransmitter acetyl choline (ACh) at neuromuscular junctions. However, this biological activity does not easily explain all the observed effects in clinical and non-clinical studies. There are also conflicting reports of expression of the BoNT/A protein receptor, SV2, and intracellular target protein, SNAP-25, in the urothelium and bladder. This review presents the current evidence of BoNT/A’s effect on bladder sensation, potential mechanisms by which it might exert these effects and discusses recent advances in understanding the action of BoNT in bladder tissue.