Health care costs, utilization and patterns of care following Lyme disease

BACKGROUND:Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome - a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. OBJECTIVES:1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. METHODS:This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. RESULTS:Lyme disease is associated with $2,968 higher total health care costs (95$3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. CONCLUSIONS:Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization

Direct Molecular Detection and Genotyping of Borrelia burgdorferi from Whole Blood of Patients with Early Lyme Disease

Direct molecular tests in blood for early Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of early Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in early Lyme disease directly from whole blood specimens prior to seroconversion

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).

ObjectiveTo evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns &lt; 28 weeks.MethodsWe performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).ResultsIndomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)).ConclusionIndomethacin was more effective than acetaminophen in producing ductus constriction

Getting the strain under control: Trans-Varestraint tests for hot cracking susceptibility

A new method for conducting Trans-Varestraint tests for assessing hot cracking susceptibility is proposed. Experiments were carried out, to validate the new method, with an industrial scale rig using tungsten inert gas welding. The hot cracking susceptibility of API-5L X65 and EN3B steel was compared. The results indicated that, by using the new method, the strain applied to the welding bead and consequently to the solidification front was controlled in a repeatable and reliable way. The results also indicated that EN3B has a maximum crack length (a parameter in the test) higher than X65 and it is reached at lower augmented strain thus demonstrating it is more susceptible to hot cracking, while also indicating that there is a capability of predicting the initiation position of hot cracks during welding. By using the method proposed, the capability of setting standardized test procedures for Trans-Varestraint tests is improved. It is recommended that future tests for assessing hot cracking susceptibility should employ the proposed method in order for the results to be comparable and to also study the effect of strain rate in hot cracking of materials

Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study

Peer reviewedPublisher PD

Longevity of daily oral Vitamin D3 supplementation:Differences in 25OHD and 24,25(OH)2D observed 2 years after cessation of a 1-year randomized controlled trial (VICtORy RECALL)

Purpose To determine the longevity of vitamin D status following cessation of vitamin D3 supplementation, 2 and 3 years after a 1 year randomised double blind placebo controlled trial: (Vitamin D and Cardiovascular Risk (VICtORY)); and to investigate possible predictive factors. Method Of the 305 Caucasian non-smoking postmenopausal women randomised to ViCtORY (2009-2010), participants who had not taken vitamin D supplements since the trial ended were invited to attend follow up visits. Total 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25OH2D) were measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation; the original RCT samples were re-analysed simultaneously. Vitamin D binding protein (VDBP) was measured by monoclonal immunoassay. Results In March 2012 and March 2013, 159 women (mean (SD) age 67.6 (2.1) years) re-attended, distributed between the original treatment groups: daily vitamin D3 400IU; 1000IU; and placebo. One month after the RCT ended (March 2010) the proportion of women in placebo, 400IU, and 1000IU vitamin D3 groups, respectively, with 25OHD0.001, n=46,44,54); 42%, 33%, 12% (2y, p=0.002,n=50,48,57) and 45%, 27%, 29% (3y, p=0.138, n=47,45,51,). VDBP was a predictor of circulating 25OHD longevity (beta for VDBP in µg/ml:0.736; 95% CI 0.216-1.255,p=0.006) but not 24,25OH2D

HP1 Recruits Activity-Dependent Neuroprotective Protein to H3K9me3 Marked Pericentromeric Heterochromatin for Silencing of Major Satellite Repeats

H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1α, HP1β and HP1γ These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1α and HP1β. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription