Advancing Pharmacological Treatments for Opioid Use Disorder (ADaPT-OUD): an Implementation Trial in Eight Veterans Health Administration Facilities

BackgroundIdentifying effective strategies to improve access to medication treatments for opioid use disorder (MOUD) is imperative. Within the Veterans Health Administration (VHA), provision of MOUD varies significantly, requiring development and testing of implementation strategies that target facilities with low provision of MOUD.ObjectiveDetermine the effectiveness of external facilitation in increasing the provision of MOUD among VHA facilities with low baseline provision of MOUD compared to matched controls.DesignPre-post, block randomized study designed to compare facility-level outcomes in a stratified sample of eligible facilities. Four blocks (two intervention facilities in each) were defined by median splits of both the ratio of patients with OUD receiving MOUD and number of patients with OUD not currently receiving MOUD (i.e., number of actionable patients). Intervention facilities participated in a 12-month implementation intervention.ParticipantsVHA facilities in the lowest quartile of MOUD provision (35 facilities), eight of which were randomly assigned to participate in the intervention (two per block) with twenty-seven serving as matched controls by block.InterventionExternal facilitation included assessment of local barriers/facilitators, formation of a local implementation team, a site visit for action planning and training/education, cross-facility quarterly calls, monthly coaching calls, and consultation.Main MeasuresPre- to post-change in the facility-level ratio of patients with an OUD diagnosis receiving MOUD compared to control facilities.Key ResultsIntervention facilities significantly increased the ratio of patients with OUD receiving MOUD from an average of 18% at baseline to 30% 1 year later, with an absolute difference of 12% (95% confidence interval [CI]: 6.6%, 17.0%). The difference in differences between intervention and control facilities was 3.0% (95% CI: − 0.2%. 6.7%). The impact of the intervention varied by block, with smaller, less complex facilities more likely to outperform matched controls.ConclusionsIntensive external facilitation improved the adoption of MOUD in most low-performing facilities and may enhance adoption beyond other interventions less tailored to individual facility contexts.     

Longitudinal In Vivo Changes in Radial Peripapillary Capillaries and Optic Nerve Head Structure in Non-Human Primates With Early Experimental Glaucoma

PurposeThere is conflicting evidence regarding whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG).MethodsSpectral domain optical coherence tomography images were acquired before and approximately every two weeks after inducing unilateral EG in nine rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes.ResultsMean ALCSD and/or MRW were the first parameters to change in eight EG eyes. RPC density changed first in the ninth. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 µm, MRW thinned by 82.3 ± 65.9 µm, RNFLT decreased by 25 ± 14 µm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in two EG eyes, whereas two EG eyes had simultaneous changes.ConclusionsIn most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.     

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.     

Cryptosporidiosis among solid organ transplant recipient attendees at a summer camp

We report a cluster of pediatric cryptosporidiosis infections among solid organ transplant recipients at a summer camp in Georgia, USA. A retrospective cohort study was conducted to investigate the risk factors for infection. A total of 118 campers attended the camp during July 23‐28, 2017. The overall attack rate among campers during the outbreak was 11% (13/118). Sanger‐based amplicon sequencing of stool specimens from 7 (80%) campers identified Cryptosporidium hominis as the suspected etiologic agent. All infected campers were heart or kidney transplant recipients receiving immunosuppressive therapy. The median reported symptom duration was 12 days (range 6‐18 days) and 9 (69.2%) were hospitalized for at least one night (median length of stay 5 days, range 2‐16 days). There were no deaths or acute rejection events attributed to infection. The results of the epidemiologic and environmental investigation suggest a recreational pool as the presumed source, although there was no direct evidence to support this. Many long‐term interventions were implemented, and there have been no further outbreaks at the camp in the following two years. This outbreak demonstrates that cryptosporidiosis may be associated with notable burden in pediatric transplant recipients, and illustrates the challenges associated with source identification and containment.     

Behaviour changes in dementia 1: Point of entry data of a prospective study

Objective. This article analyses behaviour changes in dementia at the point of entry to a longitudinal study. Design. Prospective, longitudinal study of behaviour in dementia, with autopsy follow-up. Setting. Subjects with dementia, living at home with a carer. All lived in Oxfordshire, UK. Participants. Ninety-seven people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer. Measures. At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections covering many different aspects of behaviour. The 121 main questions, with 66 further ‘nested’ questions, have been shown to have high reliability. Results. This article analyses the types of behaviour change reported by carers at the point of entry to this long-term study. Few correlations were found between behaviour and age, gender and time since onset of dementia. Some types of behaviour were significantly more prevalent in those with greater cognitive impairment. Conclusions. Many of these changes create problems for carers, for example increased aggressive behaviour, wandering, wakefulness at night, incontinence and persecutory ideas. In general, they are more prevalent in people with more severe dementia. © 1997 John Wiley & Sons, Ltd.