The use of segmented regression in analysing interrupted time series studies : an example in pre-hospital ambulance care

Peer reviewedPublisher PD

Antimigraine medication use and associated health care costs in employed patients

Migraine is under diagnosed and suboptimally treated in the majority of patients, and also associated with decreased productivity in employees. The objective of this retrospective study is to assess the antimigraine medication use and associated resource utilization in employed patients. Patients with primary diagnosis of migraine or receiving antimigraine prescription drugs were identified from an employer-sponsored health insurance plan in 2010. Medical utilization and health care costs were determined for the year of 2010. Generalized linear regression was applied to evaluate the association between health care costs and the use of antimigraine medications by controlling covariates. Of 465 patients meeting the study criteria, nearly 30% that had migraine diagnosis were prescribed antimigraine medications, and 20% that had migraine diagnosis were not prescribed antimigraine medications. The remaining 50% were prescribed antimigraine medications but did not have migraine diagnosis. Patients with antimigraine medication prescriptions showed lower frequency of emergency department visits than those without antimigraine medication prescriptions. Regression models indicated an increase in migraine-related health care costs by 86% but decreases in all-cause medical costs and total health care costs by 42 and 26%, respectively, in the antimigraine medication use group after adjusting for covariates. Employed patients experienced inadequate pharmacotherapy for migraine treatment. After controlling for covariates, antimigraine prescription drug use was associated with lower total medical utilization and health care costs. Further studies should investigate patient self-reported care and needs to manage headache and develop effective intervention to improve patient quality of life and productivity

On the Deformation of a Hyperelastic Tube Due to Steady Viscous Flow Within

In this chapter, we analyze the steady-state microscale fluid--structure interaction (FSI) between a generalized Newtonian fluid and a hyperelastic tube. Physiological flows, especially in hemodynamics, serve as primary examples of such FSI phenomena. The small scale of the physical system renders the flow field, under the power-law rheological model, amenable to a closed-form solution using the lubrication approximation. On the other hand, negligible shear stresses on the walls of a long vessel allow the structure to be treated as a pressure vessel. The constitutive equation for the microtube is prescribed via the strain energy functional for an incompressible, isotropic Mooney--Rivlin material. We employ both the thin- and thick-walled formulations of the pressure vessel theory, and derive the static relation between the pressure load and the deformation of the structure. We harness the latter to determine the flow rate--pressure drop relationship for non-Newtonian flow in thin- and thick-walled soft hyperelastic microtubes. Through illustrative examples, we discuss how a hyperelastic tube supports the same pressure load as a linearly elastic tube with smaller deformation, thus requiring a higher pressure drop across itself to maintain a fixed flow rate.Comment: 19 pages, 3 figures, Springer book class; v2: minor revisions, final form of invited contribution to the Springer volume entitled "Dynamical Processes in Generalized Continua and Structures" (in honour of Academician D.I. Indeitsev), eds. H. Altenbach, A. Belyaev, V. A. Eremeyev, A. Krivtsov and A. V. Porubo

Functional significance may underlie the taxonomic utility of single amino acid substitutions in conserved proteins

We hypothesized that some amino acid substitutions in conserved proteins that are strongly fixed by critical functional roles would show lineage-specific distributions. As an example of an archetypal conserved eukaryotic protein we considered the active site of ß-tubulin. Our analysis identified one amino acid substitution—ß-tubulin F224—which was highly lineage specific. Investigation of ß-tubulin for other phylogenetically restricted amino acids identified several with apparent specificity for well-defined phylogenetic groups. Intriguingly, none showed specificity for “supergroups” other than the unikonts. To understand why, we analysed the ß-tubulin Neighbor-Net and demonstrated a fundamental division between core ß-tubulins (plant-like) and divergent ß-tubulins (animal and fungal). F224 was almost completely restricted to the core ß-tubulins, while divergent ß-tubulins possessed Y224. Thus, our specific example offers insight into the restrictions associated with the co-evolution of ß-tubulin during the radiation of eukaryotes, underlining a fundamental dichotomy between F-type, core ß-tubulins and Y-type, divergent ß-tubulins. More broadly our study provides proof of principle for the taxonomic utility of critical amino acids in the active sites of conserved proteins

Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

\ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment

Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness

BACKGROUND: Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin. METHODS: Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS. RESULTS: We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF) cytokine and chemokine levels (TNFα, MIP-2, CCL2) and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin. CONCLUSION: These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis

Laws of biology: why so few?

Finding fundamental organizing principles is the current intellectual front end of systems biology. From a hydrogen atom to the whole cell level, organisms manage massively parallel and massively interactive processes over several orders of magnitude of size. To manage this scale of informational complexity it is natural to expect organizing principles that determine higher order behavior. Currently, there are only hints of such organizing principles but no absolute evidences. Here, we present an approach as old as Mendel that could help uncover fundamental organizing principles in biology. Our approach essentially consists of identifying constants at various levels and weaving them into a hierarchical chassis. As we identify and organize constants, from pair-wise interactions to networks, our understanding of the fundamental principles in biology will improve, leading to a theory in biology

The use of adherence aids by adults with diabetes: A cross-sectional survey

BACKGROUND: Adherence with medication taking is a major barrier to physiologic control in diabetes and many strategies for improving adherence are in use. We sought to describe the use of mnemonic devices and other adherence aids by adults with diabetes and to investigate their association with control of hyperglycemia, hyperlipidemia and hypertension. METHODS: Cross sectional survey of diabetic adults randomly selected from Primary Care practices in the Vermont Diabetes Information System. We used linear regression to examine the associations between the use of various aids and physiologic control among subjects who used oral agents for hyperglycemia, hypercholesterolemia, and hypertension. RESULTS: 289 subjects (mean age 65.4 years; 51% female) used medications for all three conditions. Adherence aids were reported by 80%. The most popular were day-of-the-week pill boxes (50%), putting the pills in a special place (41%), and associating pill taking with a daily event such as a meal, TV show, or bedtime (11%). After adjusting for age, sex, marital status, income, and education, those who used a special place had better glycemic control (A1C -0.36%; P = .04) and systolic blood pressure (-5.9 mm Hg; P = .05) than those who used no aids. Those who used a daily event had better A1C (-0.56%; P = .01) than patients who used no aids. CONCLUSION: Although adherence aids are in common use among adults with diabetes, there is little evidence that they are efficacious. In this study, we found a few statistically significant associations with adherence aids and better diabetes control. However, these findings could be attributed to multiple comparisons or unmeasured confounders. Until more rigorous evaluations are available, it seems reasonable to recommend keeping medicines in a special place for diabetic adults prescribed multiple medications

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The shadow knows: using shadows to investigate the structure of the pretransitional disk of HD 100453

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.We present GPI polarized intensity imagery of HD 100453 in Y-, J-, and K1 bands which reveals an inner gap ($9 - 18$ au), an outer disk ($18-39$ au) with two prominent spiral arms, and two azimuthally-localized dark features also present in SPHERE total intensity images (Wagner 2015). SED fitting further suggests the radial gap extends to $1$ au. The narrow, wedge-like shape of the dark features appears similar to predictions of shadows cast by a inner disk which is misaligned with respect to the outer disk. Using the Monte Carlo radiative transfer code HOCHUNCK3D (Whitney 2013), we construct a model of the disk which allows us to determine its physical properties in more detail. From the angular separation of the features we measure the difference in inclination between the disks 45$^{\circ}$, and their major axes, PA = 140$^{\circ}$ east of north for the outer disk and 100$^{\circ}$for the inner disk. We find an outer disk inclination of $25 \pm 10^{\circ}$ from face-on in broad agreement with the Wagner 2015 measurement of 34$^{\circ}$. SPHERE data in J- and H-bands indicate a reddish disk which points to HD 100453 evolving into a young debris disk.Based in part on data obtained at the Gemini Observatory via the time exchange program between Gemini and the Subaru Telescope (GS-2015A-C-1). The Gemini Observatory is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), and Ministério da Ciência, Tecnologia e Inovação (Brazil). M.T. is partly supported by JSPS KAKENHI 2680016. C.A.G. is supported under NASA Origins of Solar Systems Funding via NNG16PX39P. Y.H. is supported by Jet Propulsion Laboratory, California Institute of Technology under a contract from NASA. M.S. is supported by NASA Exoplanet Research Program NNX16AJ75G. J.K. acknowledges support from Philip Leverhulme Prize (PLP-2013-110, PI: Stefan Kraus). S.K. acknowledges support from an ERC Starting Grant (Grant Agreement No. 639889). We also thank the referee for their comments and suggestions which added clarity to this paper