Diagnosing diabetes mellitus - Do we need new criteria?

The current classification and diagnostic criteria for diabetes mellitus were introduced by the United States National Data Group in 1979 and endorsed by the World Health Organization in 1980, with modifications in 1985 and 1994. The criteria, chosen to reflect the risk of complications, were the synthesis of considerable thought and expertise and represented a consensus which, it was hoped, would prove helpful to all those involved with diabetes practising clinician, research scientist and epidemiologist alike. The inconvenience, variability and nonphysiological nature of the oral glucose tolerance test (OGTT) are well-recognised. In spite of these limitations the 2-h post-load plasma glucose has remained the standard against which all other tests have been evaluated. This article reviews the original justification for the OGTT, and in the light of more recent epidemiological research seeks to place the current diagnostic criteria for diabetes into a pathophysiological, diagnostic and prognostic perspective.

Relative role of deterministic and stochastic determinants of soil animal community: a spatially explicit analysis of oribatid mites

1. Ecologists are debating the relative role of deterministic and stochastic determinants of community structure. Although the high diversity and strong spatial structure of soil animal assemblages could provide ecologists with an ideal ecological scenario, surprisingly little information is available on these assemblages.
2. We studied species-rich soil oribatid mite assemblages from a Mediterranean beech forest and a grassland. We applied multivariate regression approaches and analysed spatial autocorrelation at multiple spatial scales using Moran's eigenvectors. Results were used to partition community variance in terms of the amount of variation uniquely accounted for by environmental correlates (e.g. organic matter) and geographical position. Estimated neutral diversity and immigration parameters were also applied to a soil animal group for the first time to simulate patterns of community dissimilarity expected under neutrality, thereby testing neutral predictions.
3. After accounting for spatial autocorrelation, the correlation between community structure and key environmental parameters disappeared: about 40% of community variation consisted of spatial patterns independent of measured environmental variables such as organic matter. Environmentally independent spatial patterns encompassed the entire range of scales accounted for by the sampling design (from tens of cm to 100 m). This spatial variation could be due to either unmeasured but spatially structured variables or stochastic drift mediated by dispersal. Observed levels of community dissimilarity were significantly different from those predicted by neutral models.
4. Oribatid mite assemblages are dominated by processes involving both deterministic and stochastic components and operating at multiple scales. Spatial patterns independent of the measured environmental variables are a prominent feature of the targeted assemblages, but patterns of community dissimilarity do not match neutral predictions. This suggests that either niche-mediated competition or environmental filtering or both are contributing to the core structure of the community. This study indicates new lines of investigation for understanding the mechanisms that determine the signature of the deterministic component of animal community assembly.

Nonclassicality Criteria from Phase-Space Representations and Information-Theoretical Constraints Are Maximally Inequivalent

We consider two celebrated criteria for defining the nonclassicality of bipartite bosonic quantum systems, the first stemming from information theoretic concepts and the second from physical constraints on the quantum phase space. Consequently, two sets of allegedly classical states are singled out: (i) the set C composed of the so-called classical-classical (CC) states—separable states that are locally distinguishable and do not possess quantum discord; (ii) the set P of states endowed with a positive P representation (P-classical states)—mixtures of Glauber coherent states that, e.g., fail to show negativity of their Wigner function. By showing that C and P are almost disjoint, we prove that the two defining criteria are maximally inequivalent. Thus, the notions of classicality that they put forward are radically different. In particular, generic CC states show quantumness in their P representation, and vice versa, almost all P-classical states have positive quantum discord and, hence, are not CC. This inequivalence is further elucidated considering different applications of P-classical and CC states. Our results suggest that there are other quantum correlations in nature than those revealed by entanglement and quantum discord.

Selection and Treatment of Data for Radiocarbon Calibration: An Update to the International Calibration (IntCal) Criteria

High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.

Revised response criteria for polycythemia vera and essential thrombocythemia:an ELN and IWG-MRT consensus project

Standardized response criteria to interpret and compare clinical trials are needed for approval of new therapeutic agents by regulatory agencies. The European LeukemiaNet (ELN) response criteria for essential thrombocythemia (ET) and polycythemia vera (PV) issued in 2009 have been widely adopted as end points in a number of recent clinical trials. However, evidence exists that they do not predict response or provide clinically relevant measures of benefit for the patients. This article presents revised recommendations for assessing response in ET and PV provided by a working group established by ELN and International Working Group-Myeloproliferative Neoplasms Research and Treatment. New definitions of complete and partial remission incorporate clinical, hematological, and histological response assessments that include a standardized symptom assessment form and consider absence of disease progression and vascular events. We anticipate that these criteria will be adopted widely to facilitate the development of new and more effective therapies for ET and PV.

Risk assessment of patient handling with ambulance stretcher systems (ramp/(winch), easi-loader, tail-lift) using biomechanical failure criteria

The research aims to carry out a detailed analysis of the loads applied by the ambulance workers when loading/unloading ambulance stretchers. The forces required of the ambulance workers for each system are measured using a load cell in a force handle arrangement. The process of loading and unloading is video recorded for all the systems to register the posture of the ambulance workers in different stages of the process. The postures and forces exerted by the ambulance workers are analyzed using biomechanical assessment software to examine if the work loads at any stage of the process are harmful. Kinetic analysis of each stretcher loading system is performed. Comparison of the kinetic analysis and measurements shows very close agreement for most of the cases. The force analysis results are evaluated against derived failure criteria. The evaluation is extended to a biomechanical failure analysis of the ambulance worker's lower back using 3DSSPP software developed at the Centre for Ergonomics at the University of Michigan. The critical tasks of each ambulance worker during the loading and unloading operations for each system are identified. Design recommendations are made to reduce the forces exerted based on loading requirements from the kinetic analysis. © 2006 IPEM.

Prevalence of potentially inappropriate prescribing and prescribing omissions in Irish adults: findings from the Irish LongituDinal Study on Ageing (TILDA)

Purpose: We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥65 years using data from The Irish LongituDinal Study on Ageing (TILDA).

Methods: A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression.

Results: The overall prevalence of PIP in the study population (n = 3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n = 1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n = 341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05–3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23–1.75 for prescribing omissions).

Conclusion: Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.

STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

PURPOSE: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required.

METHODS: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology.

RESULTS: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines.

CONCLUSION: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.