A trial of implementation facilitation to increase timely admission to methadone treatment.

BACKGROUND: During the ongoing opioid epidemic, some Opioid Treatment Programs (OTPs) are unable to admit program applicants in a timely fashion. Interim methadone (IM) treatment (without routine counseling) is an effective approach to overcome this challenge when counseling capacity is inadequate to permit admissions within 14 days of request. It requires both federal and state approval and has been rarely utilized since its incorporation into the federal OTP regulations in 1993. METHODS: We evaluated the impact of Implementation Facilitation (IF) on OTPs providing timely admission to methadone treatment (i.e., within 14 days of request), adopting IM, and changing admissions procedures. IF included data collection on admission processes and an external facilitator who engaged OTP leadership, Local Champions through site visits, remote academic detailing, and feedback. Local Champions and State Opioid Treatment Authorities (SOTAs) participated in learning collaboratives. Using a modified stepped wedge design, six OTPs in four US states on the east and west coasts were randomly assigned to one of two clusters that staggered the timing of IF receipt. Study Phases included: Pre-Implementation, IF, and Sustainability. OTPs submitted data on treatment requests and admissions for 28 months (N = 3108 requests for treatment). RESULTS: Although none of the OTPs adopted IM, all six developed policies and procedures to enable its use. Some OTPs streamlined admissions processes prior to study launch and during the IF intervention. OTPs reduced admission delays over time, although there was substantial site heterogeneity. The IF Phase for the early cluster coincided with the onset of COVID-19, complicating the study. Rates of timely admission within 14 days of request were 56.2 % (Pre-Implementation), 55.8 % (IF), and 78.8 % (Sustainability). Compared to the Pre-Implementation Phase, the odds of timely admission were not significantly different during the IF Phase but significantly higher during the Sustainability Phase (OR = 2.35 [95 % CI = 1.34, 4.12]; p = 0.003). CONCLUSIONS: Committing to study participation and IF activities may have prompted some OTPs to change practices that improved timely admission. Attributing changes to IF should be done with caution considering study limitations. Data collection for the study spanned the COVID-19 pandemic, which complicates interpretation. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT04188977.

Metamorphosis Imposes Variable Constraints on Genome Expansion through Effects on Development.

Genome size varies ∼100,000-fold across eukaryotes and has long been hypothesized to be influenced by metamorphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, join the lungfish in having the largest vertebrate genomes-3 to 40 times that of humans-as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution.

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations.

Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

Treatment options for leishmaniasis.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

Two-color Kerr microscopy of two-dimensional materials with sub-picosecond time resolution.

We present a two-color Kerr microscopy system based on two electronically synchronized erbium-fiber laser oscillators with independently tunable emission energies spanning most of the visible spectrum. Combining a spatial resolution below 2 µm and sub-ps time resolution with high sensitivity and cryogenic sample temperatures, it is ideally suited for studying spin and valley dynamics in a wide range of two-dimensional materials. We illustrate its capabilities by studying a monolayer of the common semiconducting transition metal disulfide MoS2.

HIV-Risk Behavior Among Adults with Opioid Use Disorder During 12 Months Following Pre-trial Detention: Results from a Randomized Trial of Methadone Treatment.

This was a three group randomized clinical trial of interim methadone and patient navigation involving 225 pre-trial detainees with opioid use disorder in Baltimore. The HIV Risk Assessment Battery (RAB) was administered at baseline (in jail), and at 6 and 12 months post-release. Generalized linear mixed model analyses indicated the condition × time interaction effect failed to reach significance (ps > .05) for both the drug risk and sex risk subscale scores. Therefore, findings suggest that there were no intervention effects on drug or sex risk behaviors. However, increased use of cocaine at baseline was associated with increases in drug- (b = .04, SE = .02) and sex-risk (b = .01, SE = .003) behaviors. These results suggest that interventions targeting cocaine use among pre-trial detainees may serve as a means of reducing HIV risk associated with drug- and sex-risk behaviors.Clinical Trials Registration: Clinicaltrials.gov NCT02334215.

Self-Guiding of Long-Wave Infrared Laser Pulses Mediated by Avalanche Ionization.

Nonlinear self-guided propagation of intense long-wave infrared (LWIR) laser pulses is of significant recent interest, as it promises high power transmission without beam breakup and multifilamentation. Central to self-guiding is the mechanism for the arrest of self-focusing collapse. Here, we show that discrete avalanche sites centered on submicron aerosols can arrest self-focusing, providing a new mechanism for self-guided propagation of moderate intensity LWIR pulses in outdoor environments. Our conclusions are supported by simulations of LWIR pulse propagation using an effective index approach that incorporates the time-resolved plasma dynamics of discrete avalanche breakdown sites.

Absolute Measurement of Laser Ionization Yield in Atmospheric Pressure Range Gases over 14 Decades.

Strong-field ionization is central to intense laser-matter interactions. However, standard ionization measurements have been limited to extremely low density gas samples, ignoring potential high density effects. Here, we measure strong-field ionization in atmospheric pressure range air, N_{2}, and Ar over 14 decades of absolute yield, using mid-IR picosecond avalanche multiplication of single electrons. Our results are consistent with theoretical rates for isolated atoms and molecules and quantify the ubiquitous presence of ultralow concentration gas contaminants that can significantly affect laser-gas interactions.

Methadone treatment of arrestees: A randomized clinical trial.

BACKGROUND: Opioid use disorder is common among detainees in US jails, yet methadone treatment is rarely initiated. METHODS: This is a three-group randomized controlled trial in which 225 detainees in Baltimore treated for opioid withdrawal were assigned to: (1) interim methadone (IM) with patient navigation (IM + PN); (2) IM; or (3) enhanced treatment-as-usual (ETAU). Participants in both IM groups were able to enter standard methadone treatment upon release, while ETAU participants received an assessment/referral number. Follow-up assessments at 1, 3, 6, and 12 months post-release determined treatment enrollment, urine drug testing results, self-reported days of drug use, criminal activity, and overdose events. Generalized linear mixed modelling examined two planned contrasts: (1) IM groups combined vs. ETAU; and (2) IM + PN vs. IM. RESULTS: On an intention-to-treat basis, compared to ETAU, significantly more participants in the combined IM groups were in treatment 30 days post-release, while the IM + PN vs. IM groups did not significantly differ. By month 12, there were no significant differences in the estimated marginal means of enrollment in any kind of drug treatment (0.40 and 0.27 for IM + PN and IM groups, respectively, compared to 0.29 for ETAU). There were no significant differences for either contrast in opioid-positive tests, although all groups reported a sharp decrease in heroin use from baseline to follow-up. There were five fatal overdoses, but none occurred during methadone treatment. CONCLUSION: Initiating methadone treatment in jail was effective in promoting entry into community-based drug abuse treatment but subsequent treatment discontinuation attenuated any potential impact of such treatment.

Adaptive control of laser-wakefield accelerators driven by mid-IR laser pulses.

There has been growing interest both in studying high intensity ultrafast laser plasma interactions with adaptive control systems as well as using long wavelength driver beams. We demonstrate the coherent control of the dynamics of laser-wakefield acceleration driven by ultrashort (∼ 100 fs) mid-infrared (∼ 3.9 µm) laser pulses. The critical density at this wavelength is 7.3 × 1019 cm-3, which is achievable with an ordinary gas target system. Interactions between mid-infrared laser pulses and such near-critical-density plasma may be beneficial due to much higher absorption of laser energy. In addition, the normalized vector potential of the laser field a0 increases with longer laser wavelength, lowering the required peak laser intensity to drive non-linear laser-wakefield acceleration. Here, MeV level, collimated electron beams with non-thermal, peaked energy spectra are generated. Optimization of electron beam qualities are realized through adaptive control of the laser wavefront. A genetic algorithm controlling a deformable mirror improves the electron total charge, energy spectra, beam pointing and stability at various plasma density profiles. Particle-in-cell simulations reveal that the optimal wavefront causes an earlier injection on the density up-ramp and thus higher energy gain as well as less filamentation during the interaction, which leads to the improvement in electron beam collimation and energy spectra.

Prolonged overall survival following metastasectomy in stage IV melanoma.

BACKGROUND/OBJECTIVES: Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma. METHODS: The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into 'metastasectomy' (n = 4214, 30.0%) and 'non-metastasectomy' (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan-Meier and Cox proportional hazards regressions. RESULTS: On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non-primary surgery (median survival: 7.13 month; 5-year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non-primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non-M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495-0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456-0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328-0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434-0.517)]. CONCLUSION: Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs.