Low-Dose Systemic Alteplase (tPA) for the Treatment of Pulmonary Embolism.

OBJECTIVE: To review and evaluate the evidence regarding the use of low-dose regimens of alteplase (tPA) for the treatment of pulmonary embolism (PE). DATA SOURCES: A PubMed search (1966-January 2015) was conducted using the search terms pulmonary embolism, drug therapy, thrombolytic therapy, fibrinolytic agents, and tissue plasminogen activator. Articles were cross-referenced for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and case reports published in the English language assessing the use of low-dose systemic tPA for the treatment of PE were reviewed for inclusion. DATA SYNTHESIS: tPA is a thrombolytic agent indicated for the treatment of massive and submassive PE. Major bleeding complications of tPA are dose dependent and may occur in up to 6.4% of patients. Clinical trials have demonstrated safety and efficacy of low-dose tPA, particularly showing its benefit in patients with a low body weight (<65 kg) and right-ventricular dysfunction. Furthermore, case reports have safely used lower doses of tPA in patients at higher risk of bleeding, including elderly, pregnant, and surgical patients. CONCLUSIONS: The available data suggest that low-dose tPA may be a safe and effective treatment option for acute PE, particularly in patients at a high risk of bleeding. More studies are needed to determine the optimal dosing regimen of tPA for PE.

Assessment of the Use of Pharmacologic Venous Thromboembolism Prophylaxis in Post-Traumatic Brain Injury Patients.

BACKGROUND: Traumatic brain injury (TBI) is an independent risk factor for venous thromboembolism (VTE). Prophylaxis (PPX) beyond 48 hours increases VTE risk 3- to 4-fold. Pharmacologic VTE PPX initiation is controversial due to potential bleeding complications. OBJECTIVE: To evaluate VTE PPX in patients with TBI for practice variation, efficacy, and safety. METHODS: Retrospective review from January 2013 to September 2016 in adults admitted to the intensive care unit with moderate to severe TBI. Demographics, time to stable computerized tomography scan, time to PPX initiation, PPX regimen, and incidences of VTE and adverse effects were collected. Data were analyzed via descriptive statistics, analysis of variance, and linear regression models. RESULTS: Of 96 patients included, 14.6% did not receive VTE PPX (G1), 7.3% initiated therapy within 0 to 24 hours (G2), 14.6% after 24 to 48 hours (G3), and 63.5% after 48 hours (G4). VTE occurred in 0% of G1 and G2, 28.6% of G3, and 8.2% of G4 patients (P = .038). Of 9 VTE cases, 8 received medical and 1 received trauma PPX dosing (P = .44). There were 3 major bleeds (P = .79) and 19 minor bleeds (P = .042). Of 14 fatalities, 42.9% were in G1, 0% in G2, 14.2% in G3, and 42.9% in G4 (P = .009). CONCLUSION: The majority of patients received delayed PPX, with no correlation between VTE incidence and PPX regimen. There was a significant difference in VTE incidence stratified by time to PPX. Further studies are required to determine optimal timing of PPX. Higher mortality rate was correlated with the lack of PPX. Increased minor bleeds occurred with earlier PPX initiation.

Low-barrier buprenorphine during the COVID-19 pandemic: A rapid transition to on-demand telemedicine with wide-ranging effects.

Low barrier addiction clinics increase access to medications to treat substance use disorders, while emphasizing harm reduction. The Harm Reduction and BRidges to Care (HRBR) Clinic is an on demand, low barrier addiction clinic that opened in October 2019. In the first three months of operation (November through January 2020), HRBR saw steadily increasing numbers of patients. Oregon saw its first case of novel coronavirus in February, and declared a state of emergency and enacted a formal "Stay at Home" order in March. That same month, the DEA announced that patients could be initiated on buprenorphine through telemedicine visits without an in-person exam. Within a week of being granted the ability to see patients virtually, HRBR had transitioned to over 90% virtual visits, while still allowing patients without technology to access in-person care. Within four weeks, the clinic expanded hours significantly, established workflows with community harm reduction partners, and was caring for patients in rural areas of the state. In response to the COVID-19 crisis, the HRBR clinic was able to quickly transition from in-person to almost completely virtual visits within a week. This rapid pivot to telemedicine significantly increased access to care for individuals seeking low-threshold treatment in multiple contexts. Overarching institutional support, grant funding and a small flexible team were critical. HRBR's increased access and capacity were only possible with the Drug Enforcement Agency loosening restrictions around the use of telehealth for new patients. Keeping these altered regulations in place will be key to improving health and health care equity for people who use drugs, even after the pandemic subsides. Further research is needed in to whether addiction telemedicine impacts medication diversion rates, continued substance use, or provider practices.

Sleep disturbances in CHARGE syndrome: types and relationships with behavior and caregiver well-being.

Children with CHARGE syndrome frequently develop moderate to severe behavior difficulties and are often diagnosed with obsessive-compulsive disorder, attention deficit disorder, Tourette syndrome, and autism. Anecdotal reports have indicated that sleep is also affected. However, the prevalence and types of sleep disturbance have not been identified. This study investigated sleep disturbances in 87 children with CHARGE syndrome, aged 6 to 18 years (mean 11y, SD 3y 8mo). There were 52 males and 35 females represented. Instruments included measures of sleep (Sleep Disturbances Scale for Children [SDSC]), behavior (Developmental Behaviour Checklist [DBC]), and carer well-being (Malaise Inventory). On the SDSC, 57.5% received scores considered significant for sleep disturbances, with disorders of initiating and maintaining sleep, sleep breathing, and sleep-wake transition being the most common. The SDSC was significantly correlated with the DBC (p=0.010) and the Malaise Inventory (p=0.003). Regression analysis found that both problem behavior and sleep disturbances contributed to the prediction of scores on the Malaise Inventory. Being both deaf and blind (p=0.001), experiencing frequent middle-ear infections (p=0.015), and starting to walk at an older age (p=0.007) were associated with more sleep disturbance. Craniofacial anomalies were not. The study highlights the importance of addressing the sleep difficulties associated with CHARGE syndrome relating both to airway management and to disorders of initiating sleep.

Tools to Support Hospital-Based Addiction Care: Core Components, Values, and Activities of the Improving Addiction Care Team.

: Hospitals are increasingly filled with people admitted for medical and surgical complications of substance use disorder (SUD). Hospitalization can be a reachable moment to engage and initiate SUD care. Yet most hospitals do not have systems in place to adequately address addiction, and most providers have little to no addiction training. There is widespread need for protocols and tools to implement hospital-based SUD care. We share best practices from our hospital-based Improving Addiction Care Team (IMPACT). We include a description of interprofessional roles (medical providers, social workers, peers with lived experience in recovery) and include detailed appendices of practical tools such as medication protocols (eg, buprenorphine induction), risk assessments (eg, outpatient parenteral antibiotic therapy) and treatment tools (eg, a patient safety care plan to manage patient and staff expectations surrounding risks for in hospital drug use). A case example illustrates how IMPACT works and how tools can be applied. We hope other hospitals can adapt and integrate these tools to support widespread implementation of hospital-based SUD care.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units.

BACKGROUND: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013. OBJECTIVE: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs). METHODS: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation. The primary outcomes included adherence to 4 guideline recommendations: treatment of pain before sedation, use of nonnarcotic analgesic medications, use of nonbenzodiazepine sedative medications, and use of goal-directed sedation. RESULTS: Of 138 patients evaluated, 50% had a primary medical diagnosis (as opposed to surgical, cardiac, or neurological diagnosis), and the median Sequential Organ Failure Assessment (SOFA) score was 7. Pain was treated prior to administration of sedatives in 55.4% of subjects, with fentanyl being the primary analgesic used. In addition, 19% received no analgesia, and 11.5% received nonopioid analgesia. Sedative agents were administered to 87 subjects (48 nonbenzodiazepine and 39 benzodiazepine). Of those receiving benzodiazepines, 22 received intermittent bolus regimens and 16 received continuous infusions, of which 5 were for another indication besides sedation. Validated scales measuring the degree of sedation were completed at least once in 56 (81.6%) patients receiving sedatives. CONCLUSIONS: Current sedation practices suggest that integration of evidence-based PAD guidelines across New Jersey adult ICUs is inconsistent despite pharmacist involvement.