Search

Background: Both vaccine trials and surveillance studies typically use passive surveillance systems to monitor study outcomes, which may lead to under-reporting of study outcomes in areas with poor access to care. This detection bias can have an adverse effect on conventional estimates of pneumonia risk derived from vaccine trials., Methods: We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent pneumococcal vaccine (PCV) among children less than 2 years of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographical information system. The study was conducted using 11 729 children who received three doses of any study vaccine (PCV11) or placebo. Multivariate Cox proportional hazards models were used to examine major risk factors for pneumonia diagnosis and the relationship between distance to Bohol Regional Hospital (BRH) and vaccination with PCV with risk for pneumonia diagnosis., Results: There was a significant interaction effect between distance from BRH and vaccination with PCV11 on pneumonia risk. Among children living 12 km from BRH, vaccination with PCV11 was associated with a decreased hazard ratio for radiographic pneumonia, compared with vaccination with the study placebo [0.57, 95% confidence interval (CI) 0.37-0.86). However, for children living 1 km from BRH, there was little difference in risk of radiographic pneumonia diagnosis between children vaccinated with PCV11 and those given the study placebo., Conclusion: Children living close to BRH had no documented reduction in the primary study outcome from PCV11, whereas those at greater distance experienced a substantial reduction. Because of detection bias caused by distance to BRH, in spatial analysis of vaccine trial results it may be necessary to adjust estimates of pneumonia risk and vaccine efficacy. Failure to consider the geographical dimension of trials may lead to underestimates of efficacy which might influence public health planning efforts., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Postherpetic neuralgia (PHN) develops in 8-24% of patients with herpes zoster. Few studies have evaluated the patient burden and treatment of PHN in general practice., Objectives: To determine the patient burden of PHN with respect to pain intensity and impact on patient functioning and to characterise treatment patterns and health resource utilisation in general practice., Methods: Eighty-four patients with PHN were identified in general practice settings during an observational survey of neuropathic pain syndromes in six European countries. Patients answered a questionnaire that included: pain severity and interference items from the modified short form brief pain inventory (mBPI-SF); EuroQol (EQ-5D) survey; and questions related to current treatment, health status and resource utilisation. Physicians provided information on medications prescribed for PHN and pain-related co-morbidities (anxiety, depression and sleep disturbance)., Results: Mean patient age was 71.0 +/- 12.8 years, 76% were > or = 65 years and 45% of patients had PHN > or = 1 year. The mean pain severity index was 4.2, reflecting moderate pain despite 89% of patients taking prescription medications for PHN. Few medications with demonstrated efficacy against PHN (e.g. carbamazepine and gabapentin) were prescribed, often at suboptimal doses. Pain severity was associated with reduced EQ-5D health state valuation (P<0.001), greater pain interference on all domains (P<0.001) and increased health resource utilisation (P = 0.008)., Conclusions: PHN causes substantial patient burden expressed as interference with daily functioning and reduced health status associated with pain severity. This burden may result in part from suboptimal management strategies and suggests a need for more effective pain management.

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated (r=0.53-0.74) with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.3 (serotype 19F), and 206.3 (serotype 23F). The functionality of antibodies increased after the fourth dose of vaccine (i.e., the concentration required for in vitro killing of pneumococci decreased). Both the quantity and quality of antibodies are important in the evaluation of immunogenicity of pneumococcal vaccines.

We report a culture system requiring the addition of freshly made ascorbic acid to the medium, that supports the short-term survival of adult rat olfactory receptor neurons. The cultured neurons exhibit typical voltage-gated currents and are responsive to application of odorants.

The identification of the binding sites for liver nuclear proteins present in the enhancer that control the cell specific transcription of the human apolipoprotein AII gene is reported. Five adjacent binding sites (motifs I to V) were identified. The motifs III, IV and V can be occupied differently by liver or HeLa nuclear proteins. Two hypersensitive zones (between motifs II-III and IV-V) are present only when liver nuclear extracts were tested. A first characterization of the factors reveal that motif IV interacts with the hepatic transcription factors Tf-LF1 (29) and LF-A1 (28, 30). A CCAAT binding protein, different from CTF/NF1, appears to bind to the motif II. The different binding sites share specific DNA sequences principally with 5' regulatory regions of other apolipoprotein genes.

The structure and function of the genes encoding the polypeptide components of plasma lipoproteins are of interest because of the central role they play in the regulation of lipid metabolism. We have now completed our previous studies on the human apoAI gene and furthermore isolated and sequenced cDNA clones for apoAII , CII and CIII. The nucleotide sequences show the signal peptides of apoAII , CII and CIII to be 18, 22 and 20 amino acids in length, respectively, and in addition that prepro apoAII bears a classical propeptide structure of 5 amino acids. The amino acid homology detected between apoCII and pro- apoAI is discussed, as is the gene arrangement of the 5' non-coding region of apoAI mRNA. The relative liver mRNA levels of the 4 apolipoproteins analysed in this study have been estimated and compared with their corresponding plasma products. The data reported here provide an essential basis for further studies of structural and functional alleles of apo AI, AII, CII and CIII genes.