Observation of a molecular bond between ions and Rydberg atoms.

Atoms with a highly excited electron, called Rydberg atoms, can form unusual types of molecular bonds1-4. The bonds differ from the well-known ionic and covalent bonds5,6 not only by their binding mechanisms, but also by their bond lengths ranging up to several micrometres. Here we observe a new type of molecular ion based on the interaction between the ionic charge and a flipping-induced dipole of a Rydberg atom with a bond length of several micrometres. We measure the vibrational spectrum and spatially resolve the bond length and the angular alignment of the molecule using a high-resolution ion microscope7. As a consequence of the large bond length, the molecular dynamics is extremely slow. These results pave the way for future studies of spatio-temporal effects in molecular dynamics (for example, beyond Born-Oppenheimer physics).

Observation of Vibrational Dynamics of Orientated Rydberg-Atom-Ion Molecules.

Vibrational dynamics in conventional molecules usually takes place on a timescale of picoseconds or shorter. A striking exception are ultralong-range Rydberg molecules, for which dynamics is dramatically slowed down as a consequence of the huge bond length of up to several micrometers. Here, we report on the direct observation of vibrational dynamics of a recently observed Rydberg-atom-ion molecule. By applying a weak external electric field of a few millivolts per centimeter, we are able to control the orientation of the photoassociated ultralong-range Rydberg molecules and induce vibrational dynamics by quenching the electric field. A high resolution ion microscope allows us to detect the molecule's orientation and its temporal vibrational dynamics in real space. Our study opens the door to the control of molecular dynamics in Rydberg molecules.

Zeeman optical pumping of 87Rb atoms in a hollow-core photonic crystal fiber.

Preparation of an atomic ensemble in a particular Zeeman state is a critical step of many protocols for implementing quantum sensors and quantum memories. These devices can also benefit from optical fiber integration. In this work we describe experimental results supported by a theoretical model of single-beam optical pumping of 87Rb atoms within a hollow-core photonic crystal fiber. The observed 50% population increase in the pumped F = 2, mF = 2 Zeeman substate along with the depopulation of remaining Zeeman substates enabled us to achieve a threefold improvement in the relative population of the mF = 2 substate within the F = 2 manifold, with 60% of the F = 2 population residing in the mF = 2 dark sublevel. Based on theoretical model, we propose methods to further improve the pumping efficiency in alkali-filled hollow-core fibers.

Transient Density-Induced Dipolar Interactions in a Thin Vapor Cell.

We exploit the effect of light-induced atomic desorption to produce high atomic densities (n≫k^{3}) in a rubidium vapor cell. An intense off-resonant laser is pulsed for roughly one nanosecond on a micrometer-sized sapphire-coated cell, which results in the desorption of atomic clouds from both internal surfaces. We probe the transient atomic density evolution by time-resolved absorption spectroscopy. With a temporal resolution of ≈ 1 ns, we measure the broadening and line shift of the atomic resonances. Both broadening and line shift are attributed to dipole-dipole interactions. This fast switching of the atomic density and dipolar interactions could be the basis for future quantum devices based on the excitation blockade.

Integrating two-photon nonlinear spectroscopy of rubidium atoms with silicon photonics.

We study an integrated silicon photonic chip, composed of several sub-wavelength ridge waveguides, and immersed in a micro-cell with rubidium vapor. Employing two-photon excitation, including a telecom wavelength, we observe that the waveguide transmission spectrum gets modified when the photonic mode is coupled to rubidium atoms through its evanescent tail. Due to the enhanced electric field in the waveguide cladding, the atomic transition can be saturated at a photon number ≈80 times less than a free-propagating beam case. The non-linearity of the atom-clad Si-waveguide is about 4 orders of magnitude larger than the maximum achievable value in doped Si photonics. The measured spectra corroborate well with a generalized effective susceptibility model that includes the Casimir-Polder potentials, due to the dielectric surface, and the transient interaction between flying atoms and the evanescent waveguide mode. This work paves the way towards a miniaturized, low-power, and integrated hybrid atomic-photonic system compatible with CMOS technologies.

Highly customized 1010†nm, ns-pulsed Yb-doped fiber amplifier as a key tool for on-demand single-photon generation.

The development of highly customized technical devices is a decisive feature of technically complex setups, as frequently observed in quantum experiments. This paper describes the development and realization of an Yb-doped all-fiber amplifier system designed for such a special application, more specifically, an on-demand single-photon source based on four-wave mixing with rubidium Rydberg atoms. The laser is capable of generating bandwidth-limited configurable nanosecond pulses up to peak powers of >100 W and with pulse repetition frequencies (PRF) between 50 Hz and 1 MHz at selectable wavelengths (1008-1024 nm). Especially the amplification of the 1010 nm reference seed at the lower edge of the amplification range for Yb-based fibers is challenging and tends to produce amplified spontaneous emission (ASE) at higher wavelengths. To achieve high ASE suppression, particularly at low pulse repetition frequencies, two acousto-optical modulators (AOM) are utilized both for pulse picking and for temporal filtering. The synchronization between pulse repetition frequency and AOM driver signal allows pulse amplitude fluctuations to be kept below 1%, while ASE is suppressed by at least 85 dB (PRF = 1 MHz) and 65 dB (PRF = 1 kHz).

Coupling a single electron to a Bose-Einstein condensate.

The coupling of electrons to matter lies at the heart of our understanding of material properties such as electrical conductivity. Electron-phonon coupling can lead to the formation of a Cooper pair out of two repelling electrons, which forms the basis for Bardeen-Cooper-Schrieffer superconductivity. Here we study the interaction of a single localized electron with a Bose-Einstein condensate and show that the electron can excite phonons and eventually trigger a collective oscillation of the whole condensate. We find that the coupling is surprisingly strong compared to that of ionic impurities, owing to the more favourable mass ratio. The electron is held in place by a single charged ionic core, forming a Rydberg bound state. This Rydberg electron is described by a wavefunction extending to a size of up to eight micrometres, comparable to the dimensions of the condensate. In such a state, corresponding to a principal quantum number of n = 202, the Rydberg electron is interacting with several tens of thousands of condensed atoms contained within its orbit. We observe surprisingly long lifetimes and finite size effects caused by the electron exploring the outer regions of the condensate. We anticipate future experiments on electron orbital imaging, the investigation of phonon-mediated coupling of single electrons, and applications in quantum optics.

Fiber-integrated spectroscopy device for hot alkali vapor.

We introduce an all-glass, vacuum tight, fiber-integrated and alkali compatible spectroscopy device consisting of two conventional optical fibers spliced to each end of a capillary. This is mainly realized through a decentered splicing method allowing refilling of the capillary and controlling the vapor density inside. We analyze the light guidance of the setup through simulations and measurements of the transmission efficiency at different wavelengths and show that filling it with highly reactive alkali metals is possible, and that the vapor density can be controlled reliably.

Probing an Electron Scattering Resonance using Rydberg Molecules within a Dense and Ultracold Gas.

We present spectroscopy of a single Rydberg atom excited within a Bose-Einstein condensate. We not only observe the density shift as discovered by Amaldi and Segrè in 1934, but a line shape that changes with the principal quantum number n. The line broadening depends precisely on the interaction potential energy curves of the Rydberg electron with the neutral atom perturbers. In particular, we show the relevance of the triplet p-wave shape resonance in the e^{-}-Rb(5S) scattering, which significantly modifies the interaction potential. With a peak density of 5.5×10^{14} cm^{-3}, and therefore an interparticle spacing of 1300 a_{0} within a Bose-Einstein condensate, the potential energy curves can be probed at these Rydberg ion-neutral atom separations. We present a simple microscopic model for the spectroscopic line shape by treating the atoms overlapped with the Rydberg orbit as zero-velocity, uncorrelated, pointlike particles, with binding energies associated with their ion-neutral separation, and good agreement is found.

Pulsed Rydberg four-wave mixing with motion-induced dephasing in a thermal vapor.

We report on time-resolved pulsed four-wave mixing (FWM) signals in a thermal Rubidium vapor involving a Rydberg state. We observe FWM signals with dephasing times up to 7 ns, strongly dependent on the excitation bandwidth to the Rydberg state. The excitation to the Rydberg state is driven by a pulsed two-photon transition on ns timescales. Combined with a cw de-excitation laser, a strongly directional and collective emission is generated according to a combination of the phase matching effect and averaging over Doppler classes. In contrast to a previous report (Huber et al. in Phys Rev A 90: 053806, 2014) using off-resonant FWM, at a resonant FWM scheme we observe additional revivals of the signal shortly after the incident pulse has ended. We infer that this is a revival of motion-induced constructive interference between the coherent emissions of the thermal atoms. The resonant FWM scheme reveals a richer temporal structure of the signals, compared to similar, but off-resonant excitation schemes. A simple explanation lies in the selectivity of Doppler classes. Our numerical simulations based on a four-level model including a whole Doppler ensemble can qualitatively describe the data.

Observation of ultralong-range Rydberg molecules.

Rydberg atoms have an electron in a state with a very high principal quantum number, and as a result can exhibit unusually long-range interactions. One example is the bonding of two such atoms by multipole forces to form Rydberg-Rydberg molecules with very large internuclear distances. Notably, bonding interactions can also arise from the low-energy scattering of a Rydberg electron with negative scattering length from a ground-state atom. In this case, the scattering-induced attractive interaction binds the ground-state atom to the Rydberg atom at a well-localized position within the Rydberg electron wavefunction and thereby yields giant molecules that can have internuclear separations of several thousand Bohr radii. Here we report the spectroscopic characterization of such exotic molecular states formed by rubidium Rydberg atoms that are in the spherically symmetric s state and have principal quantum numbers, n, between 34 and 40. We find that the spectra of the vibrational ground state and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)-Rb(ns), agree well with simple model predictions. The data allow us to extract the s-wave scattering length for scattering between the Rydberg electron and the ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100 meV), and to determine the lifetimes and the polarizabilities of the Rydberg molecules. Given our successful characterization of s-wave bound Rydberg states, we anticipate that p-wave bound states, trimer states and bound states involving a Rydberg electron with large angular momentum-so-called trilobite molecules-will also be realized and directly probed in the near future.

Treatment Patterns and Healthcare Resource Utilization Among Newly Diagnosed Psoriasis, Psoriatic Arthritis, Axial Spondyloarthritis, and Hidradenitis Suppurativa Patients with Past Diagnosis of an Inflammatory Condition: A Retrospective Cohort Analysis of Claims Data in the United States.

INTRODUCTION: Psoriasis (PSO), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and hidradenitis suppurativa (HS) are chronic inflammatory diseases (CIDs) often diagnosed and treated individually. However, genetic overlaps exist among CIDs, and patients with one are at risk of developing others within the same spectrum. This analysis characterized treatment patterns along with clinical and economic burdens of newly diagnosed CIDs among patients with an additional past diagnosis of PSO, PsA, axSpA, or HS. METHODS: This study used MarketScan® databases to examine demographics, treatment patterns, and healthcare resource utilization for patients with ≥ 1 claim for PSO or HS or ≥ 2 claims for PsA or axSpA, and continuous enrollment in the year before (baseline period) and following (follow-up period) the date of first diagnosis (incident diagnosis). Comorbidities and new CID diagnoses with a past diagnosis of PSO, PsA, axSpA, or HS, were examined. RESULTS: The analysis included 298,794 patients (maximum of 1202 patients with ≥ 1 incident diagnoses): 134,233 had incident PSO; 9914 had incident PsA; 115,194 had incident axSpA; and 40,655 had incident HS. Prevalence of ≥ 1 CID diagnosis among patients with past diagnosis of PSO, PsA, axSpA, or HS was 4959/134,233 (3.7%), 5256/9914 (53.0%), 3205/115,194 (2.8%), and 1180/40,655 (2.9%), respectively. In patients with incident axSpA and past PsA diagnosis, incident axSpA and past HS diagnosis, and incident HS and past PSO diagnosis, steroid and opioid use were high across baseline and follow-up periods and use of biologic disease-modifying antirheumatic drugs increased from baseline to follow-up. Disease-related costs increased absolutely and increased or remained high as a proportion of all-cause costs. CONCLUSION: Patients with newly diagnosed CIDs and additional past diagnosis of PSO, PsA, axSpA, or HS experienced high treatment utilization and healthcare costs. These findings highlight the need for payers, health technology assessment agencies, clinicians, and other stakeholders to explore the co-management of CIDs, rather than treating them separately.

Durability of Near-Complete Skin Clearance in Patients with Psoriasis Using Systemic Biologic Therapies: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Near-complete skin clearance has become a rapidly achievable treatment goal for patients with psoriasis receiving systemic biologic therapies. However, real-world evidence for durability of near-complete skin clearance and risk factors associated with loss of near-complete skin clearance is limited. METHODS: This study described durability of near-complete skin clearance (≥ 90% improvement in Psoriasis Area and Severity Index from initiation; PASI90) and identified clinical factors or patient characteristics associated with loss of PASI90 among patients with psoriasis from the CorEvitas Psoriasis Registry (April 2015-August 2021). Included patients had PASI > 5 at biologic initiation and achieved PASI90 at approximately 6 months from initiation (index). A Kaplan-Meier estimate described time to loss of treatment response over 24 months follow-up from index. Proportional hazards regression was used to identify independent predictors of loss of treatment response. RESULTS: This study included 687 patient initiations (instances of patients initiating a biologic). Following achievement of PASI90, treatment response was maintained in more than half of patient initiations (54%). Treatment response was maintained at 6, 12, and 18 months from index in an estimated 73% (95% [confidence interval] CI 70-77%), 60% (95% CI 56-63%), and 50% (95% CI 47-54%) of patient initiations, respectively. Adjusted hazards regression suggested non-White race, full-time employment, greater body weight, concomitant psoriatic arthritis, prior use of biologics, and clinically meaningful skin symptoms were associated with loss of treatment response. CONCLUSIONS: Among real-world patients with psoriasis who achieved PASI90 with biologic therapy, about one-quarter lost response at 6 months, and half lost response at 18 months. Prior use of a biologic therapy and clinically meaningful skin symptoms at index, including itch and skin pain, were associated with loss of treatment response. Therefore, dermatologists may consider focusing on patient-reported symptoms as part of any intervention designed to reduce the likelihood of loss of response to biologic therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to almost clear skin for many people. However, there is limited information available about how long almost clear skin can be maintained with biologic medications, and what predicts who is likely to lose it. To explore these questions, we examined a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and the medications they take. Out of every 100 patients, 54 maintained almost clear skin and stayed on their original medication for 2 years after first having almost clear skin. Out of every 100 patients, 73, 60, and 50 maintained almost clear skin and remained on their original medication at 6, 12, and 18 months after they had achieved this response. The results indicated that patients who were not White, worked full time, previously used a biologic medication, or had itchy and/or painful skin after they had achieved almost-clear skin were more likely to change their medication and/or no longer have almost-clear skin. These results suggest that dermatologists may consider focusing on patient-reported characteristics when deciding how to treat their patients, to reduce the likelihood that they lose their response to the medication they are prescribed.

Skin Clearance is Associated with Reduced Treatment Failure in Patients with Psoriasis: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Complete and near-complete skin clearance have become achievable treatment goals for patients with psoriasis receiving systemic biologic therapies. However, there is limited real-world evidence regarding the impact of the degree of skin clearance on biologic treatment patterns among these patients. METHODS: This longitudinal cohort study assessed the relationship between degree of skin clearance following initiation of a systemic biologic therapy and treatment failure among patients from the CorEvitas Psoriasis Registry (April 2015-August 2021). Patients had Psoriasis Area and Severity Index (PASI) score > 5 at systemic biologic therapy initiation and ≥ 1 follow-up visit(s) within 15 months of initiation. Treatment failure (discontinuation due to poor response/adverse event; addition of non-biologic therapy) and degree of skin clearance (measured by PASI) were assessed following biologic initiation. Proportional hazards regression was used to estimate the association between PASI response level and treatment failure over follow-up. RESULTS: This study included 2701 patient initiations from 2516 unique patients with 3846 total visits over follow-up. Over half of the patient initiations (n = 1412; 52.3%) were among patients with PASI >10. Treatment failure occurred in 1.3% of visits at which PASI100 was achieved, while those achieving PASI90 - < 100 and PASI75 - < 90 had treatment failure rates of 3.4% and 3.5%, respectively. After adjustment for confounders, the risk of treatment failure was two to three times higher in the PASI90 - < 100 (hazard ratio [HR] = 2.61; 95% confidence interval [CI] 1.35, 5.02; p = 0.004) and PASI75 < 90 (HR = 2.97; CI 1.58, 5.58; p = 0.001) groups compared to the PASI100 group. The risk of treatment failure was more than 20 times higher in the < PASI75 group versus the PASI100 group (HR = 22.26; CI 13.32, 37.21; p < 0.001). CONCLUSIONS: The results suggest that patients are more likely to remain on a systemic biologic therapy if they achieve near-complete or complete skin clearance, supporting the continued need to target skin clearance as a treatment goal in psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02707341.

Many people with psoriasis are often treated with biologic medications that work to improve symptoms associated with psoriasis, including inflammation. These medications can lead to clear or almost-clear skin for many people. However, there is limited information available about how achieving this goal affects whether patients continue taking their biologic medication or add a new non-biologic medication. The data source for this study was a database of patients with psoriasis (the CorEvitas Psoriasis Registry) that records how clear patients' skin is and what medications they take. Over 1 year after starting a biologic medication, approximately 1 out of every 100 patients that achieved clear skin after taking a biologic medication stopped using that medication, and approximately 3 out of every 100 patients with almost-clear skin after taking a biologic medication stopped using that medication. Meanwhile, around 20 out of every 100 patients that did not have clear or almost-clear skin after taking a biologic medication stopped using that medication. Furthermore, patients who did not have clear or almost-clear skin after taking a biologic medication had more than 20 times greater risk of stopping their medication than those who did have clear or almost-clear skin after taking a biologic medication. These results suggest that patients are more likely to remain on their biologic medication if they experience clear or almost-clear skin after taking a biologic medication and that patients and their providers should aim for this goal when taking a biologic medication.

Organic versus mixed specialist older adult inpatient mental health units for people with dementia.

Dementia presents a major public health challenge to healthcare providers globally. When older people with dementia need inpatient mental healthcare, they can be cared for in one of two different types of older adult ward. These patients can either be admitted to an organic inpatient ward for people with dementia or the subtypes of dementia, or they can be admitted to a mixed inpatient ward for older people who have either functional or organic conditions. Using a quality assurance pilot study, the authors aimed to investigate whether the quality of care for patients with dementia differed between mixed and organic inpatient wards in units exclusively serving older people. The quality of care on both types of ward was compared by analysing observed interactions between patients and staff, patient well-being and patient environment and mealtimes. The quality of care was measured with a specially developed instrument and against evidence-based standards of care. The ratings of both types of ward showed high levels of quality interactions between patients and staff. There were minimal differences in the quality of patient and staff interactions, patient well-being, and patient environment and mealtimes between the two types of ward. Further work on outcomes and carer experiences needs to be undertaken to establish the optimal care environment for people with dementia.

The Diagnostic Yield of Fetal Echocardiography Indications in the Current Era.

BACKGROUND: The aim of this study was to examine the diagnostic yield of current fetal echocardiography (FE) indications representing a recent era. METHODS: FE reports of all pregnancies referred to two provincial FE programs from 2009 to 2018 were examined, identifying the indication for FE (14 categories), gestational age at referral, and whether there was no fetal heart disease (FHD), mild or possible FHD (e.g., simple ventricular septal defect, possible coarctation), or moderate or severe FHD. RESULTS: Over the study period, there were 19,310 unique FE referrals in Alberta (23.3 ± 5.4 weeks' gestation), including 1,907 (9.9%) with moderate or severe and 654 (3.4%) with mild or possible FHD. The most common referral indications included extracardiac pathology or markers (29.7%), maternal diabetes (18.3%), suspected FHD (17.7%), and family history of heart defects (17.7%). The highest yield for moderate or severe FHD was suspected FHD (41.1%; 95% CI, 39.4%-42.7%), followed by suspected or confirmed genetic disorder (15.4%; 95% CI, 12.6%-18.2%), twins or multiples (10.6%; 95% CI, 8.7%-12.5%), oligohydramnios (8.0%; 95% CI, 4.1%-11.9%), extracardiac pathology or markers (6.4%; 95% CI, 5.8%-7.1%), and heart not well seen (5.8%; 95% CI, 4.0%-7.6%). Lowest yields were observed for maternal diabetes (2.2%; 95% CI, 1.7%-2.7%) and family history of heart defects (1.7%; 95% CI, 1.3%-2.2%). Excluding suspected FHD, with two or more FE indications, all other indications demonstrated significant increases in yield of mild or possible (3.5% vs 1.9%, P < .001) and moderate or severe (7.2% vs 2.9%, P < .001) FHD. CONCLUSIONS: Suspected FHD provides the highest diagnostic yield of moderate or severe FHD. In contrast, maternal diabetes and family history of heart defects, among the most common referral indications, had diagnostic yields approaching general population risks. Even in the absence of suspected FHD, having two or more referral indications importantly increases the diagnostic yield of all other FE indications.

A room-temperature single-photon source based on strongly interacting Rydberg atoms.

Tailored quantum states of light can be created via a transfer of collective quantum states of matter to light modes. Such collective quantum states emerge in interacting many-body systems if thermal fluctuations are overcome by sufficient interaction strengths. Therefore, ultracold temperatures or strong confinement are typically required. We show that the exaggerated interactions between Rydberg atoms allow for collective quantum states even above room temperature. The emerging Rydberg interactions lead both to suppression of multiple Rydberg state excitations and destructive interference due to polariton dephasing. We experimentally implemented a four-wave mixing scheme to demonstrate an on-demand single-photon source. The combination of glass cell technology, identical atoms, and operation around room temperature promises scalability and integrability. This approach has the potential for various applications in quantum information processing and communication.

One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry.

BACKGROUND: Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias. METHODS: Patients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching. RESULTS: Patients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups.

Adherence rates and health care costs in Crohn's disease patients receiving certolizumab pegol with and without home health nurse assistance: results from a retrospective analysis of patient claims and home health nurse data.

BACKGROUND: Patient support programs have a positive effect on adherence to therapy. Certolizumab pegol (CZP) is a tumor necrosis factor antagonist for the treatment of Crohn's disease. OBJECTIVES: To assess, using real-world claims data, whether home health nurse assistance had an effect on patients' adherence to CZP and to measure its impact on health care use and costs. METHODS: A retrospective analysis of medical and pharmacy claims data from the IQVIA Real-World Data Adjudicated Claims Database was conducted using data from January 1, 2007 through September 30, 2015. CZP patients with Crohn's disease were eligible to receive self-administration instructions from a nurse or nurse-administered CZP injections, or both. These services were provided by CIMplicity®, a home health nurse program sponsored by UCB Pharma. Cohorts were based on patients with and without nurse assistance and were matched based on gender and categorical age. Adherence to CZP was determined using the medication possession ratio (MPR) and proportion of days covered (PDC). A Kaplan-Meier analysis was performed to compare time to discontinuation of CZP between the two cohorts. Multivariate regression analyses were performed, adjusting for additional covariates to compare the effect of CZP with and without nurse assistance on hospitalization and total health care costs. RESULTS: Patients with at least 12 months of continuous enrollment post-index date were evaluated for adherence to CZP (n=276 in each cohort). The mean and median PDC and MPR values were higher with nurse assistance than without. Time to discontinuation was significantly longer in patients who received CZP with nurse assistance than without (P=0.0004). Results from the multivariate analyses showed a significant reduction in all-cause hospitalization (-55.8%; P=0.0026) and total health care costs (-14.3%; P=0.0045) with nurse assistance. CONCLUSION: This analysis suggests that home health nurse assistance increases adherence to CZP and reduces health care costs in patients with Crohn's disease.

(+)Insert smooth muscle myosin heavy chain (SM-B): from single molecule to human.

In smooth muscle, alternative mRNA splicing of a single gene produces four myosin heavy chain (SMMHC) isoforms. Two of these isoforms differ by the presence [(+)insert] or absence [(-)insert] of a seven amino acid insert in the motor domain. This insert enhances the kinetic properties of myosin at the molecular level but its exact role at the cell and tissue levels still has to be elucidated. This review focuses on the expression and biological functions of the (+)insert isoform. Current knowledge is summarized regarding its tissue distribution in animals and humans. Studies at the molecular, cellular and tissue levels that aimed at understanding the contribution of this isoform to smooth muscle mechanical function are presented with a particular focus on velocity of shortening. In addition, the altered expression of the (+)insert isoform in diseases and models of diseases and the compensatory mechanisms that occur when the (+)insert is knocked out are discussed. The need for additional studies on the relationship of this isoform to contractile performance and how expression of this isoform is regulated are also considered.