Adult attention deficit hyperactivity disorder clinic: An interprofessional collaboration.

OBJECTIVE: To review the experience of a pharmacist-led interprofessional attention deficit hyperactivity disorder (ADHD) clinic in a large integrated health care system. PRACTICE DESCRIPTION: Kaiser Permanente Northwest (KPNW) is a nonprofit managed health care system that provides integrated care to more than 625,000 members in Oregon and southwest Washington. Most health care encounters occur within KPNW facilities and with KPNW health professionals or support staff using a common electronic medical record. PRACTICE INNOVATION: A team-based adult ADHD service was implemented with collaboration among the mental health, primary care, and pharmacy departments. EVALUATION: The patients were assessed by a psychiatrist for diagnosis and care guidance. METHODS: A pharmacist, working under the collaborative drug therapy management partnership, then initiated and managed the patient's medications through telephone encounters until the patient was stable. The care of the patient was then transitioned back to primary care and not added to psychiatry's caseload. RESULTS: A total of 914 patients were treated by the adult ADHD clinic since the initiation of the service in the fall of 2015. Of these patients, 610 were stabilized successfully by the ADHD clinic pharmacists. The ADHD clinic pharmacists conducted 2634 patient encounters over the study period and averaged 3.7 telephone follow-ups per successful patient, with follow-ups approximately every 2 weeks. The organization realized a cost savings of $761,280 during this time period on the basis of the cost of a mental health provider adjusting and addressing ADHD medications versus pharmacy staff working to stabilize the patient. CONCLUSION: The implementation of a collaborative adult ADHD service has demonstrated a successful alliance of primary care, mental health, and pharmacy in a large managed care organization. In addition to increased efficiency and evidence-based practice, the adult ADHD clinic resulted in cost savings and improved access to mental health care.

Results from a clinical trial evaluating the efficacy of real-time body surface visual feedback in reducing patient motion during lung cancer radiotherapy.

INTRODUCTION: Optical surface measurement devices are a maturing technology in radiotherapy. The challenge for such devices is to demonstrate how they can improve clinical care. We present results from a phase 1 clinical trial designed to test the hypothesis that if presented with live data from a novel optical measurement device, showing their deviation from an ideal radiotherapy treatment position, patients will be able to better control their motion and increase their geometrical conformance. METHOD AND MATERIALS: Fourteen lung cancer patients were enrolled in a prospective clinical study and asked to use a variety of visual feedback schema from a novel in-house developed optical surface measurement device. The magnitude and regularity of their body surface motion using the different schema was compared to that when free-breathing at three time-points throughout their radiotherapy treatment schedule. Additionally, 4D Cone Beam CT data, acquired simultaneously with the optical measurements, was used to test if improvements in external motion are reflected in changes in internal tumor motion. RESULTS: The primary endpoint of the trial, device tolerability assessed by the fraction of participants completing all study sessions, was 86%. Secondary endpoints showed that use of the visual feedback device was found to statistically significantly decrease body surface motion magnitude by an average of 17% over the study cohort, although not universally. Similarly body surface motion variability was decreased by 18% on average. Internal tumor motion magnitude was also found to be statistically significantly decreased by an average of 14% when using the feedback device. Reduction in external motion was predictive of reduced internal motion but no evidence of a simple correlation between changes in internal and external motion magnitude was found. CONCLUSIONS: Visual feedback of live motion is well tolerated by lung cancer patients and can reduce both body surface and tumor motion.

Do perfusion and diffusion MRI predict glioblastoma relapse sites following chemoradiation?

To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60 Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HPt); hypoperfused (hPg) and hyperperfused (HPg) voxels using a histogram-based Gaussian method; diffusion-restricted voxels (DRg); and HPg voxels with diffusion restriction (HPg&DRg). Two sets of voxels (2,459,483 and 2,073,880) were analyzed according to these thresholding methods. Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %). The best PPV was obtained with HPg&DRg voxels within the FLAIR hyperintensity, as 18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 % with initial PDA (p < 0.0001). This prospective study suggests that DSC and/or DWI-MRI do not predict the glioblastoma relapse sites. However, further investigations with new methodological approaches are needed to better understand the role of these modalities in the prediction of glioblastoma relapse sites.

Overriding Felkin control: a general method for highly diastereoselective chelation-controlled additions to alpha-silyloxy aldehydes.

According to the Felkin-Anh and Cram-chelation models, nucleophilic additions to alpha-silyloxy aldehydes proceed through a nonchelation pathway due to the steric and electronic properties of the silyl group, giving rise to Felkin addition products. Herein we describe a general method to promote chelation-control in additions to alpha-silyloxy aldehydes. Dialkylzincs, functionalized dialkylzincs, and (E)-disubstituted, (E)-trisubstituted, and (Z)-disubstituted vinylzinc reagents add to silyl-protected alpha-hydroxy aldehydes with high selectivity for chelation-controlled products (dr of 10:1 to >20:1) in the presence of alkylzinc halides or triflates, RZnX. With the high functional group tolerance of organozinc reagents, the mild Lewis acidity of RZnX, and the excellent diastereoselectivities favoring the chelation-controlled products, this method will be useful in the synthesis of natural products. A mechanism involving chelation is supported by (1) NMR studies of a model substrate, (2) a dramatic increase in reaction rate in the presence of an alkylzinc halide, and (3) higher diastereoselectivity with larger alkyl substituents on the alpha-carbon of the aldehyde. This method provides access to chelation-controlled addition products with high diastereoselectivity previously unavailable using achiral organometallic reagents.

A method to combine target volume data from 3D and 4D planned thoracic radiotherapy patient cohorts for machine learning applications.

BACKGROUND AND PURPOSE: The gross tumour volume (GTV) is predictive of clinical outcome and consequently features in many machine-learned models. 4D-planning, however, has prompted substitution of the GTV with the internal gross target volume (iGTV). We present and validate a method to synthesise GTV data from the iGTV, allowing the combination of 3D and 4D planned patient cohorts for modelling. MATERIAL AND METHODS: Expert delineations in 40 non-small cell lung cancer patients were used to develop linear fit and erosion methods to synthesise the GTV volume and shape. Quality was assessed using Dice Similarity Coefficients (DSC) and closest point measurements; by calculating dosimetric features; and by assessing the quality of random forest models built on patient populations with and without synthetic GTVs. RESULTS: Volume estimates were within the magnitudes of inter-observer delineation variability. Shape comparisons produced mean DSCs of 0.8817 and 0.8584 for upper and lower lobe cases, respectively. A model trained on combined true and synthetic data performed significantly better than models trained on GTV alone, or combined GTV and iGTV data. CONCLUSIONS: Accurate synthesis of GTV size from the iGTV permits the combination of lung cancer patient cohorts, facilitating machine learning applications in thoracic radiotherapy.

Line tension at fluid membrane domain boundaries measured by micropipette aspiration.

Line tension is a determinant of fluid phase domain formation kinetics and morphology in lipid bilayer membranes, which are models for biological membrane heterogeneity. We describe the first direct measurement of this line tension by micropipette aspiration. Our data are analyzed with a model that does not rely on independently measured (and composition dependent) secondary parameters, such as bending stiffness or membrane viscosities. Line tension is strongly composition dependent and decreases towards a critical consolute point in a quasiternary room temperature phase diagram.

Flicker spectroscopy of thermal lipid bilayer domain boundary fluctuations.

This contribution describes measurements of lipid bilayer domain line tension based on two-dimensional thermal undulations of membranes with liquid ordered/liquid disordered phase coexistence and near-critical composition at room temperature. Lateral inhomogeneity of lipid and protein composition is currently a subject of avid research aimed at determining both fundamental properties and biological relevance of membrane domains. Line tension at fluid lipid bilayer membrane domain boundaries controls the kinetics of domain growth and therefore regulates the size of compositional heterogeneities. High line tension promotes membrane domain budding and fission. Line tension could therefore be an important control parameter regulating functional aspects of biological membranes. Here the established method of fluid domain flicker spectroscopy is applied to examine thermal domain wall fluctuations of phase-separated bilayer membranes. We find a Gaussian probability distribution for the first few excited mode amplitudes, which permits an analysis by means of appropriately specialized capillary wave theory. Time autocorrelation functions are found to decay exponentially, and relaxation times are fitted by means of a hydrodynamic theory relating line tensions and excited mode relaxation kinetics. Line tensions below 1 pN are obtained, with these two approaches yielding similar results. We examine experimental artifacts that perturb the Fourier spectrum of domain traces and discuss ways to identify the number of modes that yield reliable line tension information.