"Let's Talk about Physical Activity": Understanding the Preferences of Under-Served Communities when Messaging Physical Activity Guidelines to the Public.

Despite many countries having physical activity guidelines, there have been few concerted efforts to mobilize this information to the public. The aim of this study was to understand the preferences of under-served community groups about how the benefits of physical activity, and associated guidelines, can be better communicated to the public. Participatory workshops, co-developed between researchers, a local charity, and a community artist, were used to gather data from four groups in Bristol, UK: young people (n = 17); adults (n = 11); older adults (n = 5); and Somali women (n = 15). Workshop content was structured around the study aims. The community artist and/or the local charity delivered the workshops, with researchers gathering data via observation, photos, and audio-recordings, which were analysed using the framework method. All four groups noted that the benefits of physical activity should be included within any communications efforts, though not restricted to health-related benefits. Language used should be simple and jargon-free; terms such as "sedentary", "vigorous" and "intensity" were deemed inaccessible, however all groups liked the message "some is good, more is better". Views about preferred mechanisms, and messenger, for delivering physical activity messages varied both between, and within, groups. Recommendations for those working in physical activity communications, research, and policy are provided.

An International Standard for holotranscobalamin (holoTC): international collaborative study to assign a holoTC value to the International Standard for vitamin B12 and serum folate.

BACKGROUND: Investigation of possible B12 and folate deficiencies requires measurement of these vitamins in serum. There is evidence that holotranscobalamin (holoTC), the active portion of B12 available to cells, is a more specific marker of early B12 deficiency than total B12. The availability of immunoassays for holoTC prompted an international collaborative study to assign a holoTC value to the World Health Organization (WHO) 1st International Standard (IS) for vitamin B12 and serum folate, 03/178. METHODS: The IS, 03/178, and three serum samples with different holoTC levels were assayed by 12 laboratories in eight countries using manual and automated immunoassays for holoTC; one laboratory additionally performed an in-house assay. Fourteen sets of data were analysed. RESULTS: Overall, the IS, 03/178, and the three serum samples demonstrated assay linearity and parallelism. An overall geometric mean (GM) holoTC value of 106.8 pmol/L was obtained for 03/178, with an inter-laboratory geometric coefficient of variation (GCV) of 10.5%. There was a reduction in inter-laboratory variability when the holoTC levels in the serum samples were determined relative to the IS with an assigned holoTC value rather than to the assays' calibration. Accelerated degradation studies showed that 03/178 was sufficiently stable to serve as an IS for holoTC. CONCLUSIONS: The WHO Expert Committee on Biological Standardization endorsed the proposal to assign a holoTC value of 107 pmol/L to 03/178, corresponding to 0.107 pmol per ampoule, for use as the 1st IS for vitamin B12, serum folate, and holoTC.

Guidelines for the diagnosis and treatment of cobalamin and folate disorders.

The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no 'gold standard' test to define deficiency. Serum cobalamin currently remains the first-line test, with additional second-line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first-line test, but an indeterminate 'grey area' may still exist. Plasma homocysteine may be helpful as a second-line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited. Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established. In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment. Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue. Serum folate offers equivalent diagnostic capability to red cell folate and is the first-line test of choice to assess folate status.

Isotope dilution-LC-MS/MS reference method assessment of serum folate assay accuracy and proficiency testing consensus mean.

BACKGROUND: Current methods for measuring folates in clinical laboratories are competitive folate binding protein assays. These assays show a considerable lack of agreement that has implications for the comparability of data across studies as well as for long-term population studies. The development of isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference methods permitted the evaluation of method accuracy and consistency over time. METHODS: We measured 3 pools of human serum by ID-LC-MS/MS, calculated values for total folate, and distributed the same pools to participants in a national External Quality Assessment scheme. We used linear regression to compare the all-laboratory and method data with reference method values. The exercise was repeated after 18 months to assess the stability of the all-laboratory and method data. RESULTS: The distributed serum pools had mass spectrometry values for folate species typical of those found in healthy individuals from populations not receiving dietary folic acid fortification. There was good agreement of the all-laboratory data set with the reference method (y =0.86x + 0.91 µg/L) at both time points. Linear regression demonstrated that the Abbott Architect showed the closest agreement with the reference method. The Roche Elecsys method was nonlinear and showed a calibration offset of 2.6 µg/L (4.57 nmol/L). CONCLUSIONS: Calibration of serum folate assays traceable to higher-order reference methods increases method accuracy and improves consistency. The all-laboratory consensus mean proved sufficiently accurate and stable to be used as the target for monitoring laboratory performance.

An IgG complexed form of vitamin B12 is a common cause of elevated serum concentrations.

OBJECTIVES: To report detailed investigations in a case of elevated serum B(12) due to the presence of an IgG-B(12) complex, to determine the prevalence of this phenomenon and to review the literature. DESIGN AND METHODS: 431 samples with elevated B(12) (median 1250 ng/L, range 901-114,480 ng/L) were treated with polyethylene glycol to precipitate immunoglobulin complexes. Samples with >50% of precipitable B(12) (PPB(12)) were further investigated by protein G adsorption, gel filtration chromatography and measurement of B(12) on different analytical platforms. RESULTS: Median PPB(12) was 22.6%, but in 35 samples (8.1%), median PPB(12) was more than 50%. Investigation of 27 of these samples with protein G-Sepharose confirmed the presence of an IgG-B(12) complex in 24, and in 15 cases, B(12) fell to within the reference range. After treatment of serum with reagents releasing B(12) from binding proteins, immunoreactivity co-eluted with free B(12). Immunoreactivity of the IgG-bound form of B(12) was confirmed using five B(12) assays in common use in the UK. CONCLUSIONS: At least 8% of samples with elevated vitamin B(12) contain an immunoglobulin complexed form of circulating B(12); this possibility should be considered in the interpretation of results.

Myocardial scarring following chemotherapy for multiple myeloma detected using late gadolinium hyperenhancement cardiovascular magnetic resonance.

We present the case of a 60-year-old lady who was treated with chemotherapy for myeloma. Following initiation of bortezomib, she developed heart failure which was associated with a reduction in left ventricular systolic function. A gadolinium enhanced cardiovascular magnetic resonance scan demonstrated midwall hyperenhancement consistent with midwall fibrosis.

Automated immunoassay methods for ferritin: recovery studies to assess traceability to an international standard.

BACKGROUND: Ferritin standardisation is problematical due to the heterogeneity of ferritin isoforms and the antibodies used in its immunoassay, and the lack of a reference measurement procedure. We investigated the performance of the 1st (liver), 2nd (spleen) and 3rd (recombinant) International Standards (ISs) for ferritin in major assays. METHODS: The ferritin in a serum pool 'spiked' with either the 2nd or 3rd IS for ferritin was measured by 52 laboratories using five automated methods and the recovery of the target values calculated. A smaller serum pool was 'spiked' with the 1st IS for a limited recovery exercise. The ferritin values of five serum samples were also measured and recalculated relative to the ISs. RESULTS: Recoveries of each of the 2nd and 3rd ISs were 90%-110% for four of five methods; recoveries of the 1st IS were 104% and 111% for two of three methods claiming traceability to this IS. One method significantly over-recovered each of the IS (124%-155%). Recalculating the ferritin values of the serum samples relative to the IS reduced the overall inter-method agreement, largely because of the anomalous over-recovery of the IS by one method. CONCLUSIONS: The use of the 3rd IS to standardise assays will minimise assay drift due to manufacturers adopting a 'harmonisation' approach in which the calibration is adjusted to conform to overall mean values. Standardisation against the current IS also ensures compliance with the European Union In-Vitro Diagnostic Directive which requires traceability of assay calibrators to reference materials of a higher order. Assay drift may result in poor sensitivity and specificity in the diagnosis of iron status, and would require laboratories to continually re-evaluate reference intervals.

International Standard for serum vitamin B(12) and serum folate: international collaborative study to evaluate a batch of lyophilised serum for B(12) and folate content.

BACKGROUND: Vitamin B(12) and folate measurements in serum show wide inter-methodology variability. This variability appears to be due in part to the lack of standardisation against internationally accepted reference materials. Pooled human serum, lyophilised in ampoules and designated 03/178, was therefore evaluated by 24 laboratories in seven countries for its suitability to serve as an International Standard (IS) for B(12) and folate. METHODS: IS 03/178 was assayed using a range of commercial analysers, microbiological assays and, for folate, candidate reference methods based on liquid chromatography coupled to isotope-dilution tandem mass spectrometry (LC/MS/MS). RESULTS: Mean vitamin B(12) and folate values for reconstituted 03/178 across all laboratories and methods were 480 pg/mL [coefficient of variation (CV) 12.8%] and 5.52 ng/mL (CV 17.1%), respectively. The total folate content of reconstituted 03/178, determined using LC/MS/MS, was 12.1 nmol/L (equivalent to 5.33 ng/mL), made up of 9.75 nmol/L 5-methyl tetrahydrofolic acid (5MeTHF; CV 5.5%), 1.59 nmol/L 5-formyl tetrahydrofolic acid (5FoTHF; CV 4.2%) and 0.74 nmol/L folic acid (FA; CV 31.6%). The inclusion of three serum samples in the study with different B(12) and folate levels demonstrated a considerable reduction in inter-laboratory variability when the B(12) and folate content of the samples was determined relative to the IS 03/178 rather than to the analyser calibration. IS 03/178 demonstrated satisfactory long-term stability in accelerated degradation studies. CONCLUSIONS: Use of IS 03/178 to standardise serum B(12) and folate assays reduced inter-laboratory variability. The World Health Organization (WHO) Expert Committee on Biological Standardisation established 03/178 as the first IS for serum vitamin B(12) and serum folate, with assigned values of 480 pg/mL of vitamin B(12) and 12.1 nmol/L folate when the lyophilised contents of the ampoule are reconstituted with 1 mL of water.

An International Standard for whole blood folate: evaluation of a lyophilised haemolysate in an international collaborative study.

Folate measurements, particularly for whole blood, show wide inter-laboratory and inter-methodology variability. This variability appears to be due in part to the lack of internationally accepted reference materials. A whole blood haemolysate, lyophilised in ampoules and designated 95/528, was therefore evaluated by 15 laboratories in five countries for its suitability as an International Standard (IS) for whole blood folate. The preparation was assayed using a variety of microbiological and protein-binding methodologies against local standards and calibrators. A consensus folate content was assigned to 95/528. The inclusion of three whole blood samples in the study with widely differing folate levels demonstrated a considerable reduction in inter-laboratory variability when the folate content of the samples was determined relative to the proposed IS 95/528 rather than to laboratories' local standards and calibrators. Accelerated degradation studies indicated that the folate content of 95/528 is stable when stored at -20 degrees C. On the basis of the results presented here, the World Health Organization Expert Committee on Biological Standardization established 95/528 as an IS for whole blood folate.