Surveys of Substance Use Disorders Education in US Pharmacy Programs

Introduction: Substance use disorders (SUDs) are a significant US health problem affecting roughly 20 million Americans, but there continues to be limited access to SUD treatment and inadequate addiction medicine training. Therefore, it is important to understand how SUD education is being delivered to US health professionals, including pharmacists. Methods: A recent survey of US pharmacy programs\u27 neuropsychiatry curricula was evaluated to identify any progress made toward increasing SUD education since the last national survey in 2004 and determine any remaining gaps between what is currently being taught and American Association of Colleges of Pharmacy (AACP) curricular guidelines for SUD education updated in 2010. A survey of psychiatric pharmacists, regarding what they thought should be taught, was also evaluated and compared with the 2010 AACP curricular guidelines. Results: Our survey of US pharmacy programs demonstrated that 94% of programs reported teaching SUD content in 2014-15, which has increased from 81% reported in a survey study from 2004. There was also an increase for average hours of SUD didactic instruction, which increased from 2.2 hours in 2004 to 2.7 hours in 2015. The majority of members (84%) recommended at least 2 hours of SUD instruction, and 27% recommended teaching ≥4 hours. Discussion: There was an overall increase in SUD instruction, but the average hours taught still falls short of 2010 AACP curricular guideline recommendation suggesting ≥4 hours. Furthermore, a majority of the psychiatric pharmacists we surveyed did not agree with the AACP curricular guideline recommendation because only 27% of members recommended ≥4 hours of SUD instruction, and the average hours recommended was only 2.7 hours

Defining the role of dexmedetomidine in the prevention of delirium in the intensive care unit (ICU)

Dexmedetomidine is a highly selective α2 agonist used as a sedative agent. It also provides anxiolysis and sympatholysis without significant respiratory compromise or delirium. We conducted a systematic review to examine whether sedation of patients in the intensive care unit (ICU) with dexmedetomidine was associated with a lower incidence of delirium as compared to other nondexmedetomidine sedation strategies. A search of PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews yielded only three trials from 1966 through April 2015 that met our predefined inclusion criteria and assessed dexmedetomidine and outcomes of delirium as their primary endpoint. The studies varied in regard to population, comparator sedation regimen, delirium outcome measure, and dexmedetomidine dosing. All trials are limited by design issues that limit our ability definitively to conclude that dexmedetomidine prevents delirium. Evidence does suggest that dexmedetomidine may allow for avoidance of deep sedation and use of benzodiazepines, factors both observed to increase the risk for developing delirium. Our assessment of currently published literature highlights the need for ongoing research to better delineate the role of dexmedetomidine for delirium prevention

Clinical effectiveness of baclofen for the treatment of alcohol dependence: A review

Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor, possesses pharmacologic properties that may confer utility for the treatment of alcohol dependence. Research suggests that not only can it be useful in promoting maintenance of alcohol abstinence but also it may play a key role in decreasing alcohol cravings and anxiety often associated with alcohol dependence. To assess the benefit of baclofen for alcohol dependence, a review of the literature was conducted to identify published data investigating this off-label treatment. Four randomized controlled trials to date have been published and were included in this review. Although primary outcomes differ between studies, patients randomized to baclofen experience higher rates of abstinence from alcohol than those taking placebo in two of the trials. Secondary analyses indicate that baclofen is safe in patients with alcohol dependence, including those with moderate to severe liver cirrhosis, and may provide beneficial anxiolytic effects. Despite some positive data, the largest available randomized controlled trial failed to find any differences between baclofen and placebo. In all studies, individuals with severe medical comorbidities, seizure disorders, and psychiatric disorders were excluded from trials, which may limit external validity. In summary, there may be beneficial effects from using baclofen for the treatment of alcohol dependence; however, limited conclusions can be drawn from the small number of studies currently available for review. Larger well-designed trials are needed to further define baclofen’s role for the treatment of alcohol dependence

Copeptin as a Prognostic Marker in Acute Chest Pain and Suspected Acute Coronary Syndrome

: Background. In patients admitted with chest pain and suspected acute coronary syndrome (ACS), it is crucial to early identify those who are at higher risk of adverse events. The study aim was to assess the predictive value of copeptin in patients admitted to the emergency department with chest pain and nonconclusive ECG. Methods. Consecutive patients suspected for an ACS were enrolled prospectively. Copeptin and high-sensitive troponin T (hs-TnT) were measured at admission. Patients were followed up at six and 12 months for the occurrence of death and major adverse cardiac and cerebrovascular events (MACCE). Results. Among 154 patients, 11 patients died and 26 experienced MACCE. Mortality was higher in copeptin-positive than copeptin-negative patients with no difference in the rate of MACCE. Copeptin reached the AUC 0.86 (0.75-0.97) for prognosis of mortality at six and 0.77 (0.65-0.88) at 12 months. It was higher than for hs-TnT and their combination at both time points. Copeptin was a strong predictor of mortality in the Cox analysis (HR14.1 at six and HR4.3 at 12 months). Conclusions. Copeptin appears to be an independent predictor of long-term mortality in a selected population of patients suspected for an ACS. The study registration number is ISRCTN14112941

Vemurafenib and dabrafenib downregulates RIPK4 level

Vemurafenib and dabrafenib are BRAF kinase inhibitors (BRAFi) used for the treatment of patients with melanoma carrying the V600E BRAF mutation. However, melanoma cells develop resistance to both drugs when used as monotherapy. Therefore, mechanisms of drug resistance are investigated, and new molecular targets are sought that could completely inhibit melanoma progression. Since receptor-interacting protein kinase (RIPK4) probably functions as an oncogene in melanoma and its structure is similar to the BRAF protein, we analyzed the impact of vemurafenib and dabrafenib on RIPK4 in melanomas. The in silico study confirmed the high similarity of BRAF kinase domains to the RIPK4 protein at both the sequence and structural levels and suggests that BRAFi could directly bind to RIPK4 even more strongly than to ATP. Furthermore, BRAFi inhibited ERK1/2 activity and lowered RIPK4 protein levels in BRAF-mutated melanoma cells (A375 and WM266.4), while in wild-type BRAF cells (BLM and LoVo), both inhibitors decreased the level of RIPK4 and enhanced ERK1/2 activity. The phosphorylation of phosphatidylethanolamine binding protein 1 (PEBP1) - a suppressor of the BRAF/MEK/ERK pathway - via RIPK4 observed in pancreatic cancer did not occur in melanoma. Neither downregulation nor upregulation of RIPK4 in BRAF- mutated cells affected PEBP1 levels or the BRAF/MEK/ERK pathway. The downregulation of RIPK4 inhibited cell proliferation and the FAK/AKT pathway, and increased BRAFi efficiency in WM266.4 cells. However, the silencing of RIPK4 did not induce apoptosis or necroptosis. Our study suggests that RIPK4 may be an off-target for BRAF inhibitors

Zaburzenia funkcji poznawczych u chorych poddanych zabiegom pomostowania naczyń wieńcowych

Streszczenie Duży postęp w technikach chirurgicznych, anestezjologii, sposobach perfuzji oraz opiece pooperacyjnej spowodował obniżenie chorobowości i śmiertelności po zabiegach kardiochirurgicznych. Nadal jednak poważnymi powikłaniami po zabiegach chirurgicznej rewaskularyzacji mięśnia sercowego są zaburzenia neurologiczne. Często pomijanym zagadnieniem są zaburzenia poznawcze występujące u pacjentów po zabiegu operacyjnym. Najczęściej obserwowane są zaburzenia pamięci, koncentracji uwagi, mowy, orientacji przestrzennej, funkcji uczenia się i myślenia. Osłabienie funkcji poznawczych wydłuża okres rekonwalescencji po zabiegu, pogarsza funkcjonowanie pacjenta w rodzinie i społeczeństwie. Funkcje poznawcze to czynności psychiczne, które służą człowiekowi do uzyskania orientacji w otoczeniu, zdobycia informacji o sobie samym, analizowania sytuacji, formułowania wniosków, a także podejmowania właściwych decyzji i działań. Do funkcji poznawczych należą: spostrzeganie, uwaga, uczenie się, pamięć i myślenie. Do oceny funkcji poznawczych stosowane są metody neurofizjologiczne oraz neuropsychologiczne. Pierwsze z nich to metody obiektywne takie jak potencjały wywołane, przewodnictwo nerwów, mapowanie EKG, pomiar rytmów szybkich i ich rozkład na mapie mózgu oraz czynnościowe badania za pomocą metod obrazowych. Badanie neuropsychologiczne obejmuje wywiad kliniczny, obserwację zachowania pacjenta oraz testy neuropsychologiczne. Wyniki testów nauropsychologicznych należy interpretować w kontekście aktualnych uwarunkowań biologicznych, psychologicznych i społecznych badanej osoby. Częstość występowania zaburzeń funkcji poznawczych u chorych poddanych pomostowaniu naczyń wieńcowych waha się w zakresie od 31% do 73%. Szeroki zakres wartości podawanych w literaturze związany jest z różnymi technikami operacyjnymi stosowanymi w analizowanych grupach chorych, różnymi kryteriami włączenia i wyłączenia, odmiennymi zasadami rozpoznawania dysfunkcji poznawczych, stosowaniem różnych testów neuropsychologicznych, a także różnymi odstępami czasowymi pomiędzy przeprowadzanymi ocenami i odstępami od zabiegu operacyjnego. W porównywaniu wyników badań analizujących występowanie zaburzeń poznawczych istotna jest nie tylko technika zabiegu, ale również preferencje różnych operatorów nawet w obrębie tego samego ośrodka. Niektóre spośród tych różnic proceduralnych takie jak technika zaklemowania aorty czy też stopień hipotermii mogą być istotne z punktu widzenia protekcji mózgu podczas zabiegu. Leczenie zaburzeń poznawczych obejmuje terapię farmakologiczną (leki prokognitywne)             i neuropsychologiczną (psychologiczna interwencja kryzysowa i rehabilitacja neuropsychologiczna). Interwencja kryzysowa polega na stosowaniu wsparcia emocjonalnego i informacyjnego. Rehabilitacja neuropsychologiczna to zorganizowana forma profesjonalnego oddziaływania skierowana do osób z zaburzeniami wyższych czynności umysłowych, których celem jest zminimalizowanie lub zlikwidowanie objawów dysfunkcji. W wielu przypadkach celem oddziaływań jest odbudowa utraconej funkcji przy wykorzystaniu innych obszarów mózgu. W przypadku zmian nieodwracalnych celem oddziaływań staje się kompensacja, czyli wytworzenie innych lub wzmocnienie zachowanych funkcji poznawczych, które pozwolą lepiej radzić sobie z powstałym deficytem

Combined Use of High-Sensitive Cardiac Troponin, Copeptin, and the Modified HEART Score for Rapid Evaluation of Chest Pain Patients.

Clinical short-term risk stratification is a recommended approach in patients with chest pain and possible acute myocardial infarction (AMI) to further improve high safety of biomarker-based rule-out algorithms. The study aim was to assess clinical performance of baseline concentrations of high-sensitivity cardiac troponin T (hs-TnT) and copeptin and the modified HEART score (mHS) in early presenters to the emergency department with chest pain. This cohort study included patients with chest pain with onset maximum of 6 h before admission and no persistent ST-segment elevation on electrocardiogram. hs-TnT, copeptin, and the mHS were assessed from admission data. The diagnostic and prognostic value for three baseline rule-out algorithms: (1) single hs-TnT < 14 ng/l, (2) hs-TnT < 14 ng/l/mHS ≤ 3, and (3) hs-TnT < 14 ng/l/mHS ≤ 3/copeptin < 17.4 pmol/l, was assessed with sensitivity and negative predictive value. Primary diagnostic endpoint was the diagnosis of AMI. Prognostic endpoint was death and/or AMI within 30 days. Among 154 enrolled patients, 44 (29%) were classified as low-risk according to the mHS; AMI was diagnosed in 105 patients (68%). For ruling out AMI, the highest sensitivity and NPV from all studied algorithms were observed for hs-TnT/mHS/copeptin (100%, 95% CI 96.6-100, and 100%, 95% CI 75.3-100). At 30 days, the highest event-free survival was achieved in patients stratified with hs-TnT/mHS/copeptin algorithm (100%) with 100% (95% CI 75.3-100) NPV and 100% (95% CI 96.6-100) sensitivity. The combination of baseline hs-TnT, copeptin, and the mHS has an excellent sensitivity and NPV for short-term risk stratification. Such approach might improve the triage system in emergency departments and be a bridge for inclusion to serial blood sampling algorithms