Retrospective analysis of a pilot pharmacist-led hospice deprescribing program initiative.

CONTEXT: Medication deprescribing in palliative care settings has been insufficiently studied. OBJECTIVE: To determine the feasibility of a deprescribing program in hospice patients with limited life expectancy. DESIGN: Pharmacist-led, single arm, single-centered, retrospective analysis of a pilot deprescribing program in an integrated healthcare delivery organization between 9/1/2018 to 1/31/2019. OUTCOME MEASURES: The primary outcome was the proportion of patients who achieved ≥50% reduction of the recommended medications to deprescribe. RESULTS: A total of 97 patients were included in the analysis. The average age was 77.5 ± 23.7 years, with 53.6% being women and 54.6% white. The most common primary diagnosis was cancer (58.8%), with cardiovascular disease the next most common (15.5%). The mean number of baseline comorbidities was 2.0 ± 1.6. Of 698 prescriptions at the start of hospice enrollment, 79.4% of patients achieved a ≥50% reduction in medications recommended for deprescribing. This success was seen mostly in cardiovascular and other nonspecific medications. We found that every 1-unit increase in the number of patient encounters with hospice pharmacists was associated with a 3.2-fold higher odds of achieving a ≥50% reduction in medications that were recommended for deprescribing. CONCLUSION: The findings from this pilot study revealed that a collaborative, pharmacist-led, collaborative medication deprescribing program initiative was associated with a 79% success in ≥50% medication reduction. More frequent patient encounters had higher odds of success. Future studies, utilizing a control group, should focus on determining the effectiveness of the program and the impact on quality of life.

Cytotoxic effects of ellagitannins isolated from walnuts in human cancer cells.

Walnuts contain many bioactive components that may slow cancer growth. A previous report showed that a diet supplemented with walnuts decreased the tumor size formed by MDA-MB-231 human cancer cells injected into nude mice. However, the mechanism of action was never determined. We characterized the effects of a methanol extract prepared from walnuts on human MDA-MB-231, MCF7, and HeLa cells. The extract was cytotoxic to all cancer cells. We identified compounds from the methanol extract that induced this cytotoxicity. The predominant compounds were Tellimagrandin I and Tellimagrandin II, members of the ellagitannin family. We also show a walnut extract decreases the intracellular pH, depolarizes the mitochondrial membrane with release of cytochrome c and phosphatidylserine flipping. The antimitogenic effects of walnut extract were associated with a twofold reduction of mitochondria respiration. These results suggest impairment of mitochondrial function and apoptosis as relevant mechanism of anticancer effects of the walnut extract.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update: focus on rehabilitation and exercise and surgical coronary revascularization.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides focused discussions on the management recommendations on 2 topics: (1) exercise and rehabilitation; and (2) surgical coronary revascularization in patients with heart failure. First, all patients with stable New York Heart Association class I-III symptoms should be considered for enrollment in a tailored exercise training program, to improve exercise tolerance and quality of life. Second, selected patients with suitable coronary anatomy should be considered for bypass graft surgery. As in previous updates, the topics were chosen in response to stakeholder feedback. The 2013 Update also includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers manage their patients with heart failure.

Incidence of hydromorphone-induced neuroexcitation in hospice patients.

BACKGROUND AND OBJECTIVE: To date, there are no known published studies that prospectively followed hospice patients receiving hydromorphone to evaluate the development of hydromorphone-induced neuroexcitation (HINE). The first objective of this study was to determine the incidence of HINE. The second objective was to identify factors influencing the presence or absence of HINE symptoms in hospice patients. METHODS: This was a noninterventional, prospective study. This study population included hospice patients 18 years of age or older who were admitted to one of two Nathan Adelson Hospice inpatient units in Las Vegas, Nevada, and were initiated on a scheduled regimen of hydromorphone. A total of 156 patients were enrolled and analyzed in this study. Data collection was performed by the study investigators using a standard data tracking form, including hospice diagnosis, gender, renal function, hydromorphone regimen, and whether or not the patient experienced neuroexcitatory symptoms. Data collection occurred from November 2010 to March 2011. RESULTS AND CONCLUSIONS: Based on the data collected in this study, it appears that the likelihood of HINE does increase with larger doses, increasing age, increasing serum creatinine, and the presence of malignant neoplasm. However, after adjusting for the variables in the logistic regression model, diagnosis of malignant neoplasm was not a significant predictor of HINE. Future studies may focus on evaluating metabolite levels, such as hydromorphone-3-glucuronide (H3G), in patients developing HINE symptoms. This may help to determine if the metabolites of opioids, such as H3G, are involved in the development of the neurotoxic symptoms.

Addition of the electrocardiogram to the preparticipation examination of college athletes.

OBJECTIVE: Although the use of standardized cardiovascular (CV) system-focused history and physical examination is recommended for the preparticipation examination (PPE) of athletes, the addition of the electrocardiogram (ECG) has been controversial. Because the impact of ECG screening on college athletes has rarely been reported, we analyzed the findings of adding the ECG to the PPE of Stanford athletes. DESIGN: For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. SETTING: Although the use of standardized CV-focused history and physical examination are recommended for the PPE of athletes, the addition of the ECG has been controversial. Because the feasibility and outcomes of ECG screening on college athletes have rarely been reported, we present findings derived from the addition of the ECG to the PPE of Stanford athletes. For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. MAIN OUTCOME MEASURES: Six hundred fifty-eight recordings were obtained (54% men, 10% African-American, mean age 20 years) representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete right bundle branch block (RBBB) (13%), right axis deviation (RAD) (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for left ventricular hypertrophy (LVH) were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7%, and only 5 men had abnormal Q-waves. Sixty-three athletes (10%) were judged to have distinctly abnormal ECG findings possibly associated with conditions including hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy. These athletes were offered further testing but this was not mandated according to the research protocol. RESULTS: Six hundred fifty-three recordings were obtained (54% men, 7% African American, mean age 20 years), representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete RBBB (13%), RAD (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for LVH were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7% and only 5 men had abnormal Q-waves. Sixty-five athletes (10%) were judged to have distinctly abnormal ECG findings suggestive of arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, and/or biventricular hypertrophy. These athletes will be submitted to further testing. CONCLUSIONS: Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.

Rest premature ventricular contractions on routine ECG and prognosis in heart failure patients.

BACKGROUND: Premature ventricular contractions (PVC) at rest are frequently seen in heart failure (HF) patients but conflicting data exist regarding their importance for cardiovascular (CV) mortality. This study aims to evaluate the prognostic value of rest PVCs on an electrocardiogram (ECG) in patients with a history of clinical HF. METHODS AND RESULTS: We considered 352 patients (64 + or - 11 years; 7 females) with a history of clinical HF undergoing treadmill testing for clinical reasons at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) (1987-2007). Patients with rest PVCs were defined as having > or = 1 PVC on the ECG prior to testing (n = 29; 8%). During a median follow-up period of 6.2 years, there were 178 deaths of which 76 (42.6%) were due to CV causes. At baseline, compared to patients without rest PVCs, those with rest PVCs had a lower ejection fraction (EF) (30% vs 45%) and the prevalence of EF < or = 35% was higher (75% vs 41%). They were more likely to have smoked (76% vs 55%).The all-cause and CV mortality rates were significantly higher in the rest PVCs group (72% vs 49%, P = 0.01 and 45% vs 20%, P = 0.002; respectively). After adjusting for age, beta-blocker use, rest ECG findings, resting heart rate (HR), EF, maximal systolic blood pressure, peak HR, and exercise capacity, rest PVC was associated with a 5.5-fold increased risk of CV mortality (P = 0.004). Considering the presence of PVCs during exercise and/or recovery did not affect our results. CONCLUSION: The presence of PVC on an ECG is a powerful predictor of CV mortality even after adjusting for confounding factors.

Development of agents that modulate protein-protein interactions in membranes.

Membrane proteins account for approximately one third of all proteins in eukaryotic and prokaryotic cells. These proteins are critical in a diverse array of cellular functions. Despite their obvious importance, the effectiveness of research tools to study the structure and function of integral membrane proteins lags behind that of water-soluble proteins. This is due in part to the lack of probing agents that can specifically and selectively recognize these targets. This review focuses on methods developed to overcome the obstacles of studying membrane proteins. We describe TM protein properties as well as biophysical properties of amino acids within the membrane bilayer. We also summarize the known characteristics of membrane regions in their distinctive environments and generate a summary of current research approaches that succeed in probing interactions of TM proteins within their native setting. This allows further insight into protein-protein interactions in a hydrophobic environment as it pertains to drug development.

Adding an electrocardiogram to the pre-participation examination in competitive athletes: a systematic review.

No matter how rare, the death of young athletes is a tragedy. Can it be prevented? The European experience suggests that adding the electrocardiogram (ECG) to the standard medical and family history and physical examination can decrease cardiac deaths by 90%. However, there has not been a randomized trial to demonstrate such a reduction. While there are obvious differences between the European and American experiences with athletes including very differing causes of athletic deaths, some would highlight the European emphasis on public welfare vs the protection of personal rights in the USA. Even the authors of this systematic review have differing interpretation of the data: some of us view screening as a hopeless battle against Bayes, while others feel that the ECG can save lives. What we all agree on is that the USA should implement the American Heart Association 12-point screening recommendations and that, before ECG screening is mandated, we need to gather more data and optimize ECG criteria for screening young athletes.