An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis

Background: The purpose of using preventative inhaled treatments in cystic fibrosis is to improve health outcomes. Therefore, understanding the relationship between adherence to treatment and health outcome is crucial. Temporal variability, as well as absolute magnitude of adherence affects health outcomes, and there is likely to be a threshold effect in the relationship between adherence and outcomes. We therefore propose a pragmatic algorithm-based clustering method of objective nebulizer adherence data to better understand this relationship, and potentially, to guide clinical decisions. Methods to cluster adherence data: This clustering method consists of three related steps. The first step is to split adherence data for the previous 12 months into four 3-monthly sections. The second step is to calculate mean adherence for each section and to score the section based on mean adherence. The third step is to aggregate the individual scores to determine the final cluster (“cluster 1” = very low adherence; “cluster 2” = low adherence; “cluster 3” = moderate adherence; “cluster 4” = high adherence), and taking into account adherence trend as represented by sequential individual scores. The individual scores should be displayed along with the final cluster for clinicians to fully understand the adherence data. Three illustrative cases: We present three cases to illustrate the use of the proposed clustering method. Conclusion: This pragmatic clustering method can deal with adherence data of variable duration (ie, can be used even if 12 months’ worth of data are unavailable) and can cluster adherence data in real time. Empirical support for some of the clustering parameters is not yet available, but the suggested classifications provide a structure to investigate parameters in future prospective datasets in which there are accurate measurements of nebulizer adherence and health outcomes

Tipperary: Irish Love Song

VERSE 1I’m in love with a slip of a tip tip typical Tipperary miss:She’s a regular clip with a rosy lip that you’d dearly love to kiss.From the tip of her toes to the tip tip top of her nose I love her so.I’d like to just take her and squeeze her,I know that it wouldn’t displease her.But she lives in Tipperary many miles away from here,if I could just meet her to see her and greet her,I’m thinkin’ I’d eat her the little dear.But she’s many miles away from here and so I’ll wait I fear.Till I take a notion and sail o’er the ocean to Ireland. CHORUSFaith it’s me that’s nearly crazy,From me Tipperary daisyAll the day me hearts “unaisy.”Sure the thing I find that’s on me mind,Is the darlin’ girl I left behind,Far off in dear old Tipperary. VERSE 2Now I’ll give ye a tip when I board the ship with me grip to trip away:I’ll be there with a yell when they ring the bell and I’ll shout “hip hip hoo ray.”Then the whistle will toot and away we’ll shoot with a toot toot down the bay.I’ll wave a bye bye when we’re sailin’ from over the top of the railin’.Then across the briny ocean to the tiny Em’rald Isle I’d give me last penny, if I hadn’t any, begory, or many to see her smile.As she used to when she sat ferninst me down be side the stile.But I was a rover bedad, and came over from Ireland. CHORU

Consistency of QTL for Dollar Spot Resistance Between Greenhouse and Field Inoculations, Multiple Locations, and Different Population Sizes in Creeping Bentgrass

Dollar spot caused by Sclerotinia homoeocarpa F. T. Bennett is the most economically important turf disease in North America. Previous work indicated differences among cultivars in their susceptibility to dollar spot (Bonos et al., 2003). Studies have indicated that dollar spot resistance might be quantitatively inherited (Bonos et al., 2003) but the number, location and effect of genomic regions conferring resistance is still not known. Therefore the objective of this research is to understand the effect of population size, inoculation assays, and field locations on QTL for dollar spot resistance in creeping bentgrass

Predictors of Comorbid Eating Disorders and Association with Other Obsessive-Compulsive Spectrum Disorders in Trichotillomania

Trichotillomania (TTM) and eating disorders (ED) share many phenomenological similarities, including ritualized compulsive behaviors. Given this, and that comorbid EDs may represent additional functional burden to hair pullers, we sought to identify factors that predict diagnosis of an ED in a TTM population. Subjects included 555 adult females (age range 18–65) with DSM-IV-TR TTM or chronic hair pullers recruited from multiple sites. 7.2% (N = 40) of our TTM subjects met criteria for an ED in their lifetime. In univariable regression analysis, obsessive-compulsive disorder (OCD), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) worst-ever compulsion and total scores, certain obsessive-compulsive spectrum disorders, anxiety disorder, attention-deficit/hyperactivity disorder (ADHD), and substance disorder all met the pre-specified criteria for inclusion in the multivariable analysis. In the final multivariable model, diagnosis of OCD (OR: 5.68, 95% CI: 2.2–15.0) and diagnosis of an additional body-focused repetitive behavior disorder (BFRB) (OR: 2.69, 95% CI: 1.1–6.8) were both associated with increased risk of ED in TTM. Overall, our results provide further support of the relatedness between ED and TTM. This finding highlights the importance of assessing for comorbid OCD and additional BFRBs in those with TTM. Future research is needed to identify additional predictors of comorbid disorders and to better understand the complex relationships between BFRBs, OCD and EDs

Hemodynamic Effects of a High-Frequency Oscillatory Ventilation Open-Lung Strategy in Critically Ill Children With Acquired or Congenital Cardiac Disease

OBJECTIVES: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury.DESIGN: Secondary analysis of prospectively collected data.SETTING: Medical-surgical PICU.PATIENTS: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p &lt; 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p &lt; 0.0002) and arterial pH significantly improved ( p &lt; 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found.CONCLUSIONS: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury.</p

Efavirenz Is Predicted To Accumulate in Brain Tissue: an In Silico, In Vitro, and In Vivo Investigation

Adequate concentrations of efavirenz in the central nervous system (CNS) are necessary to suppress viral replication, but high concentrations may increase the likelihood of CNS adverse drug reactions. The aim of this investigation was to evaluate the efavirenz distribution in the cerebrospinal fluid (CSF) and the brain by using a physiologically based pharmacokinetic (PBPK) simulation for comparison with rodent and human data. The efavirenz CNS distribution was calculated using a permeability-limited model on a virtual cohort of 100 patients receiving efavirenz (600 mg once daily). Simulation data were then compared with human data from the literature and with rodent data. Wistar rats were administered efavirenz (10 mg kg of body weight(−1)) once daily over 5 weeks. Plasma and brain tissue were collected for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median maximum concentrations of drug (C(max)) were predicted to be 3,184 ng ml(−1) (interquartile range [IQR], 2,219 to 4,851 ng ml(−1)), 49.9 ng ml(−1) (IQR, 36.6 to 69.7 ng ml(−1)), and 50,343 ng ml(−1) (IQR, 38,351 to 65,799 ng ml(−1)) in plasma, CSF, and brain tissue, respectively, giving a tissue-to-plasma ratio of 15.8. Following 5 weeks of oral dosing of efavirenz (10 mg kg(−1)), the median plasma and brain tissue concentrations in rats were 69.7 ng ml(−1) (IQR, 44.9 to 130.6 ng ml(−1)) and 702.9 ng ml(−1) (IQR, 475.5 to 1,018.0 ng ml(−1)), respectively, and the median tissue-to-plasma ratio was 9.5 (IQR, 7.0 to 10.9). Although it is useful, measurement of CSF concentrations may give an underestimation of the penetration of antiretrovirals into the brain. The limitations associated with obtaining tissue biopsy specimens and paired plasma and CSF samples from patients make PBPK modeling an attractive tool for probing drug distribution

Am I my brother’s keeper? on personal identity and responsibility

The psychological continuity theory of personal identity has recently been accused of not meeting what is claimed to be a fundamental requirement on theories of identity - to explain personal moral responsibility. Although they often have much to say about responsibility, the charge is that they cannot say enough. I set out the background to the charge with a short discussion of Locke and the requirement to explain responsibility, then illustrate the accusation facing the theory with details from Marya Schechtman. I aim some questions at the challengers' reading of Locke, leading to an argument that the psychological continuity theory can say all that it needs to say about responsibility, and so is not in any grave predicament, at least not with regard to this particular charge.Web of Scienc