The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Effects of thymic selection of the T cell repertoire on HLA-class I associated control of HIV infection

Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals (‘elite controllers’) maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57 (ref. 1). Because HLA molecules present viral peptides that activate CD8+ T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.Mark and Lisa Schwartz FoundationNational Institutes of Health (U.S.) (Director’s Pioneer award)Philip T. and Susan M. Ragon FoundationJane Coffin Childs Memorial Fund for Medical ResearchBill & Melinda Gates FoundationNational Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health (U.S.) (contract no. HHSN261200800001E)National Institutes of Health (U.S.). Intramural Research ProgramNational Cancer Institute (U.S.)Center for Cancer Research (National Cancer Institute (U.S.)

Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP) : evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users

BACKGROUND: 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. METHODS: Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. RESULTS: Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (<100mcg/kg). Users make conscious and 'informed' decisions about DNP; are well-prepared for the side-effects and show nonchalant attitude toward self-experimentation with DNP. Steps are often taken to ensure that DNP is genuine. Personal experience with performance- and appearance enhancing substances appears to be a gateway to DNP. Advice on DNP and experiences are shared online. The significant discrepancy between the normative perception and the actual visibility suggests that DNP use is-contrary to the Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. CONCLUSION: Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements

Genomics meets HIV-1

Genomics is now a core element in the effort to develop a vaccine against HIV-1. Thanks to unprecedented progress in high-throughput genotyping and sequencing, in knowledge about genetic variation in humans, and in evolutionary genomics, it is finally possible to systematically search the genome for common genetic variants that influence the human response to HIV-1. The identification of such variants would help to determine which aspects of the response to the virus are the most promising targets for intervention. However, a key obstacle to progress remains the scarcity of appropriate human cohorts available for genomic research

Active children through individual vouchers – evaluation (ACTIVE): protocol for a mixed method randomised control trial to increase physical activity levels in teenagers

BackgroundMany teenagers are insufficiently active despite the health benefits of physical activity (PA). There is strong evidence to show that inactivity and low fitness levels increase the risk of non-communicable diseases such as coronary heart disease (CHD), type 2 diabetes and breast and colon cancers (Lee et al. Lancet 380:219–29, 2012). A major barrier facing adolescents is accessibility (e.g. cost and lack of local facilities). The ACTIVE project aims to tackle this barrier through a multi-faceted intervention, giving teenagers vouchers to spend on activities of their choice and empowering young people to improve their fitness and PA levels.DesignACTIVE is a mixed methods randomised control trial in 7 secondary schools in Swansea, South Wales. Quantitative and qualitative measures including PA (cooper run test (CRT), accelerometery over 7 days), cardiovascular (CV) measures (blood pressure, pulse wave analysis) and focus groups will be undertaken at 4 separate time points (baseline, 6 months,12 months and follow-up at 18 months). Intervention schools will receive a multi-component intervention involving 12 months of £20 vouchers to spend on physical activities of their choice, a peer mentor scheme and opportunities to attend advocacy meetings. Control schools are encouraged to continue usual practice. The primary aim is to examine the effect of the intervention in improving cardiovascular fitness.DiscussionThis paper describes the protocol for the ACTIVE randomised control trial, which aims to increase fitness, physical activity and socialisation of teenagers in Swansea, UK via a voucher scheme combined with peer mentoring. Results can contribute to the evidence base on teenage physical activity and, if effective, the intervention has the potential to inform future physical activity interventions and policy

Population ecology of the sea lamprey (Petromyzon marinus) as an invasive species in the Laurentian Great Lakes and an imperiled species in Europe

The sea lamprey Petromyzon marinus (Linnaeus) is both an invasive non-native species in the Laurentian Great Lakes of North America and an imperiled species in much of its native range in North America and Europe. To compare and contrast how understanding of population ecology is useful for control programs in the Great Lakes and restoration programs in Europe, we review current understanding of the population ecology of the sea lamprey in its native and introduced range. Some attributes of sea lamprey population ecology are particularly useful for both control programs in the Great Lakes and restoration programs in the native range. First, traps within fish ladders are beneficial for removing sea lampreys in Great Lakes streams and passing sea lampreys in the native range. Second, attractants and repellants are suitable for luring sea lampreys into traps for control in the Great Lakes and guiding sea lamprey passage for conservation in the native range. Third, assessment methods used for targeting sea lamprey control in the Great Lakes are useful for targeting habitat protection in the native range. Last, assessment methods used to quantify numbers of all life stages of sea lampreys would be appropriate for measuring success of control in the Great Lakes and success of conservation in the native range

Modifying Hofstee standard setting for assessments that vary in difficulty, and to determine boundaries for different levels of achievement.

BACKGROUND: Fixed mark grade boundaries for non-linear assessment scales fail to account for variations in assessment difficulty. Where assessment difficulty varies more than ability of successive cohorts or the quality of the teaching, anchoring grade boundaries to median cohort performance should provide an effective method for setting standards. METHODS: This study investigated the use of a modified Hofstee (MH) method for setting unsatisfactory/satisfactory and satisfactory/excellent grade boundaries for multiple choice question-style assessments, adjusted using the cohort median to obviate the effect of subjective judgements and provision of grade quotas. RESULTS: Outcomes for the MH method were compared with formula scoring/correction for guessing (FS/CFG) for 11 assessments, indicating that there were no significant differences between MH and FS/CFG in either the effective unsatisfactory/satisfactory grade boundary or the proportion of unsatisfactory graded candidates (p > 0.05). However the boundary for excellent performance was significantly higher for MH (p < 0.01), and the proportion of candidates returned as excellent was significantly lower (p < 0.01). MH also generated performance profiles and pass marks that were not significantly different from those given by the Ebel method of criterion-referenced standard setting. CONCLUSIONS: This supports MH as an objective model for calculating variable grade boundaries, adjusted for test difficulty. Furthermore, it easily creates boundaries for unsatisfactory/satisfactory and satisfactory/excellent performance that are protected against grade inflation. It could be implemented as a stand-alone method of standard setting, or as part of the post-examination analysis of results for assessments for which pre-examination criterion-referenced standard setting is employed