Paliative Care and Cholestrol

1. Paliative Care and Cholestrol

2. Obesity • July 8, 2011 (Washington DC)— A new report illustrates in stark terms how the obesity epidemic in the US has spiraled in the past two decades and pinpoints, on a state-by-state basis, where the largest increases have occurred [1]. The authors stress, however, that ranking the states in this way is not a reproof; rather, "we want to raise awareness, drive action, identify solutions, and reverse the epidemic." • "F as in fat: How obesity threatens American's future 2011," a report from the Trust for America's Health (TFAH) and the Robert Wood Johnson Foundation (RWJF), shows that the problem is greatest in the South, which has nine of the 10 states with the highest adult obesity rates. Mississippi holds the dubious title of state with the highest adult obesity rate, for the seventh year in a row, and obesity has grown fastest in Alabama, Oklahoma, and Tennessee. • For the first time, the report looks at how obesity levels have altered over the past 20 years; two decades ago, no state had an obesity rate above 15%, whereas now, 12 states have rates above 30% (even just four years ago, only one state had a rate above 30%). Two out of three states have obesity rates over 25%; just one, Colorado, has a rate lower than 20%. • "Today, the state with the lowest obesity rate would have had the highest rate in 1995," says Dr Jeff Levi (executive director, TFAH) in a statement [2]. "There was a clear tipping point in our national weight gain over the past 20 years, and we can't afford to ignore the impact obesity has on our health." • In terms of childhood and adolescent obesity, more than one-third of children aged 10 to 17 are obese (16.4%) or overweight (18.2%), and Mississippi again tops the poll, with a rate of 21.9%, with nine other states, plus DC, having childhood obesity rates >20%. • The report points out the inverse relationship between educational attainment and income and obesity and invites readers to "imagine what it is like to live in a neighborhood where there are no supermarkets, sidewalks, or community playgrounds, where being outside may not be safe, and joining a gym is not an option." • The aim is to help promote change by advocating a number of policies that are backed by scientific research and likely to make an impact quickly, particularly for those people whose options have been most limited. These include initiatives aimed at improving access to affordable healthy foods and safe places for children to walk, bike, and play in the communities hardest hit by the epidemic and with the fewest resources. • Late Thursday, the American Heart Association issued a statement highlighting the TFAH report, calling the rise in obesity rates "astonishing" and calling on Americans "to recognize the severity of the obesity crisis" and "the need for collective action among food manufacturers, restaurants, government and consumers to change the direction we are headed."

3. NSAID’s • July 14, 2011 (Gainesville, Florida)— Older patients with hypertension and coronary artery disease who use nonsteroidal anti-inflammatory drugs (NSAIDs) chronically for pain are at significantly increased risk of cardiovascular events, a new post hoc analysis from the International Verapamil-Trandolapril Study (INVEST) demonstrates [1]. The research is published in the July 2011 issue of the American Journal of Medicine. • "We found a significant increase in adverse cardiovascular outcomes, primary driven by an increase in cardiovascular mortality," lead author Dr Anthony A Bavry (University of Florida, Gainesville) told heartwire. "This is not the first study to show there is potential harm with these agents, but I think it further solidifies that concern." • He says the observational study, conducted within the hypertension trial INVEST, is particularly relevant to everyday practice because the patients included were typical of those seen in internal-medicine, geriatric, and cardiology clinics--they were older, with hypertension and clinically stable CAD. • Bavry and colleagues were not able to differentiate between NSAIDs in the study--most people were taking ibuprofen, naproxen, or celecoxib--and he says until further work is done, he considers the risks of NSAIDs "a class effect," and their use should be avoided wherever possible. • I try to get them to switch to an alternative agent, such as acetaminophen. • However, "Patients should not terminate these medicines on their own," he says. "They should have a discussion with their physician. When I see patients like these taking NSAIDs I will have an informed discussion with them and tell them there is evidence that these agents may be associated with harm. I try to get them to switch to an alternative agent, such as acetaminophen, or if that's not possible I at least try to get them to reduce the dose of NSAID or the frequency of dosing. But ultimately, it's up to them if this potential risk is worth taking depending upon the indication for their use." • Chronic NSAID Use More Than Doubles CV Mortality • Within the large cohort of more than 22 000 patients in INVEST, Bavry and colleagues identified patients who reported taking NSAIDs at every follow-up visit and termed them chronic users (n=882). Most often, patients were taking these agents for conditions such as rheumatoid arthritis, osteoarthritis, and lower back pain, Bavry said. • They compared the chronic NSAID users with those who only intermittently (n=7286) or never (n=14 408) used NSAIDs over an average of 2.7 years and adjusted the findings for potential confounders. • The primary outcome--a composite of all-cause death, nonfatal MI, or nonfatal stroke--occurred at a rate of 4.4 events per 100 patient-years in the chronic-NSAID group vs 3.7 events per 100 patient-years in the nonchronic group (adjusted hazard ratio 1.47; p=0.0003). • As noted by Bavry, the end point was primarily driven by a more than doubling in the risk of death from CV causes in the chronic-NSAID group compared with never or infrequent users (adjusted HR 2.26; p<0.0001). • The association did not appear to be due to elevated blood pressure, the researchers say, because chronic NSAID users actually had slightly lower on-treatment BP over the follow-up period. • They note that a recent American Geriatrics Society panel on the treatment of chronic pain in the elderly recommends acetaminophen as a first-line agent and suggests that nonselective NSAIDs or COX-2 inhibitors be used only with extreme caution. "Our findings support this recommendation," they state. • Bavry added: "We do need more studies to further characterize the risks of these agents, which are widely used and widely available, and perhaps the risks are underappreciated. We are working on the next level of studies to try to identify which are the most harmful agents."

4. Algorithm for Treatment of Hypertension in the ElderlyACEI indicates angiotensin-converting enzyme inhibitor; ALDO ANT, aldosterone antagonist; ARB, aldosterone receptor blocker; BB, beta blocker; CA, calcium antagonist; CAD, coronary artery disease; CVD, cardiovascular disease; DBP, diastolic blood pressure; RAS, renin-angiotensin system; SBP, systolic blood pressure; and THIAZ, thiazide diuretic.

5. Breast Cancer and OCs: Still Worried After All These Years? • Two studies confirm that oral contraceptives are not associated with breast cancer–specific or all-cause mortality. • Epidemiologic studies have yielded reassuring findings that oral contraceptives (OCs) do not raise risk for developing breast cancer (JW Womens Health Aug 20 2002). To evaluate risk for all-cause or breast cancer–related death in women with invasive breast cancer who used OCs, investigators assessed mortality of 4565 participants in the Women's Contraceptive and Reproductive Experiences (CARE) Study (a population-based case-control study) and 3929 participants in the California Teachers Study (CTS; a cohort study). • No associations were observed between OC use and breast cancer–specific mortality in the CARE study (828 breast cancer deaths; median follow-up, 8.6 years) or the CTS (261 breast cancer deaths; median follow-up, 6.1 years). In addition, no association was observed between OC use and all-cause mortality (CARE relative risk, 1.01; CTS RR, 0.84). Lower risk for all-cause death (but not breast cancer–related death) was observed in those CTS participants who used OCs for 10 years (RR, 0.67); however, no trend for decreasing risk with increasing OC duration was observed (P for trend, 0.22).

6. Don't Miss the New AHA Recommendations on Triglycerides • A new scientific statement raises the threshold for pharmacologic treatment of hypertriglyceridemia. • The following was published as a "Voices" blog on CardioExchange, an online forum for cardiology news and discussion. The blog prompted a lively conversation, which you can access and join by registering for CardioExchange. • I've been surprised at the lack of fanfare surrounding the American Heart Association's recently published scientific statement on triglycerides and cardiovascular disease (CVD). The attention it did receive focused on the lower fasting triglyceride level that is now considered optimal: <100 mg/dL. In my opinion, the real headline was the committee's important statements in support of less drug treatment — in particular, the recommendation for a substantial increase in the triglyceride level that should trigger consideration of pharmacologic therapy. • After a careful review of the recent literature, the committee concluded that pharmacologic therapy should not be started until a patient's fasting triglyceride level is 500 mg/dL (in contrast to the Adult Treatment Panel's recommendation of 200 mg/dL). See the figure, which also appears on page 2308 of the AHA statement. • The AHA committee also explicitly acknowledges (on page 2297) that "the independence of triglyceride level as a causal factor in promoting CVD remains debatable. Rather, triglyceride levels appear to provide unique information as a biomarker of risk, especially when combined with low HDL-C and elevated LDL-C." This clear statement — together with the new, higher threshold for initiating drug treatment — represents a remarkable change. • Meanwhile, on April 20, Abbott announced that sales of its flagship fenofibrate drugs increased by 28% in the first quarter.

7. Cumulative Antibiotic Exposure Is Associated with Risk for C. difficile Infection • In a retrospective study among hospitalized patients, higher cumulative dose, number, and duration of antibiotics were independently associated with greater risk. • Antibiotic therapy is a major risk factor for Clostridium difficile infection (CDI), but little is known about the effect of cumulative exposure. To explore this issue, researchers performed a retrospective cohort study involving adults who were hospitalized at a Rochester, New York, medical center in 2005 and received antibiotics for 2 consecutive days during their stay. • For each day of antibiotic exposure, the total dose of each agent was calculated. Daily doses were standardized according to the WHO Defined Daily Dose system. The number of different antibiotics and the duration of exposure were also calculated. • A total of 10,154 hospitalizations involving 7792 unique patients met study criteria. The incidence of CDI in this group was 4.3 per 10,000 patient-days. Factors significantly associated with increased CDI risk included older age, gastrointestinal procedures, HIV infection, history of CDI, higher chronic disease score, longer length of stay, and receipt of antacid therapy, including proton-pump or histamine-2 inhibitors. In addition, CDI risk rose, in a dose-dependent manner, with increases in cumulative dose, number, and days of antibiotics. Risk was 7.8-fold higher in patients with >18 antibiotic days than in those with <4 days and 9.6-fold higher in patients who received five or more antibiotics than in those who received only one. Intravenous cephalosporins, β-lactamase inhibitor combinations, sulfa drugs, fluoroquinolones, and vancomycin were all associated with an increased risk for CDI.

8. Does the HbA1c Criterion for Prediabetes Predict Incident Diabetes? • Measuring both fasting glucose and glycosylated hemoglobin levels might be the best method. • The American Diabetes Association recently added a new criterion for diagnosis of prediabetes — glycosylated hemoglobin (HbA1c) level of 5.7% to 6.4%. To evaluate this new criterion, Japanese investigators studied 6241 people who had five or six consecutive annual health examinations that included measurements of fasting glucose and HbA1c levels. • At their baseline examinations, 2092 patients were identified as prediabetic: 60% by impaired fasting glucose (IFG; 100–125 mg/dL) alone, 20% by HbA1c alone, and 20% by both tests. During a mean 4.7-year follow-up, 338 patients progressed to diabetes, of whom 292 (86%) had been identified as prediabetic at baseline: 32% by IFG alone, 9% by HbA1c alone, and 46% by both tests. Both IFG alone and HbA1c alone predicted incident diabetes equally strongly, with multivariate-adjusted hazard ratios of about 6, compared with that for baseline normoglycemia. Patients who were prediabetic by both criteria at baseline were 32 times more likely to progress to diabetes than those who were normoglycemic. • Comment: These results are similar to those from a U.S. data set (Diabetes Care 2010; 33:2190). Impaired fasting glucose and HbA1c measure different aspects of dysglycemia and, together, provide more sensitive and specific prediction of excess risk for diabetes than does either one alone. However, whether this accuracy improves clinically meaningful long-term outcomes remains unclear.

9. The Latest Word on Pot and Susceptibility to Psychosis • A meta-analysis indicates a specific association between cannabis use and earlier onset of psychosis. • Marijuana evokes psychotic-like symptoms in susceptible individuals (see JW Psychiatry Mar 14 2011), and cannabis use may be associated with an earlier age of onset of psychotic illness. But does marijuana cause psychosis, or are the people who are destined to become psychotic more likely to use the drug? With more than 16 million regular pot smokers in the U.S., the question is important. This meta-analysis of 83 studies of the age at onset of psychosis involved 8167 psychosis patients who used psychoactive substances and 14,352 nonusing psychosis patients. • The results confirmed that the age at onset of psychosis was almost 3 years earlier in cannabis users than in nonusers. Alcohol use was not significantly associated with earlier onset of psychosis. Studies with a higher percentage of cannabis users reported an earlier mean age at psychosis onset. The association was not explained by sex, schizophrenia versus affective psychosis, study methodology, or, to a lesser extent, patient age at the time of the study. • Comment: Because alcohol use was not associated with a younger age at onset of psychosis, the results do not suggest that people who are going to develop psychosis just start using drugs earlier than people who are less vulnerable to psychosis. Still, it is not known whether people who would not otherwise become psychotic might develop a chronic psychosis after prolonged cannabis use, as has been noted with amphetamine use. Also unknown is whether the risk results from a primary toxic effect, from an interaction of cannabis with dopamine metabolism or with an intracellular signal, or from an effect of the drug on brain maturation in adolescents. Regardless of pathogenesis, even if a psychotic illness is to develop anyway, avoiding marijuana may delay its onset or reduce its severity.

10. Parenteral Nutrition in ICU Patients: What's the Rush? • Delaying intravenous nutrition for 1 week led to fewer infectious complications, shorter length of stay, and lower hospital costs than did early initiation. • Guidelines differ substantially in their recommendations about when to start parenteral nutrition in critically ill patients; these guidelines are based primarily on expert opinion. To evaluate prospectively the optimal timing of nutritional support, investigators in Belgium randomized 4640 nutritionally at-risk patients in the intensive care unit (ICU; ~85% surgical patients, including 60% who underwent cardiac surgery) to receive early initiation (ICU day 3) or late initiation (ICU day 8) of parenteral nutrition. The study was not blinded, but allocation was concealed. • Although no differences were noted in mortality (ICU, in-hospital, or 90-day) between the groups, the late-initiation group had significantly shorter lengths of stay (LOS) in the ICU (3 vs. 4 days) and in the hospital (14 vs. 16 days); fewer infections, including fewer lung, bloodstream, and wound infections (22.8% vs. 26.2%, number needed to treat [NNT], 29); shorter mean duration of mechanical ventilation; and lower costs (~US$1600 less per patient). Surprisingly, surgical patients in the late-initiation group for whom early enteral nutrition was contraindicated benefited substantially in lower infection rate (30% vs. 40% for similar early-initiation patients; NNT, 10) and shorter ICU LOS. • Comment: This well-designed study reveals that the early routine administration of parenteral nutrition in critically ill, nutritionally at-risk patients leads to worse outcomes. Delaying parenteral nutrition for at least 1 week should be standard practice for surgical ICU patients. Although this study included relatively few medical ICU patients (~500), this conclusion also can be reasonably applied to such patients, unless new evidence becomes available.

11. First-Trimester SSRI Exposure and Congenital Anomalies • Specific antidepressants are associated with risk for cardiovascular or neural-tube defects in a population-based study. • Studies have only inconsistently linked cardiovascular anomalies with first-trimester exposure to selective serotonin reuptake inhibitors (SSRIs). The very low base rates of these anomalies require researchers to use large samples to detect statistically significant differences. The current researchers examined the issue in a retrospective study using Finnish national registries. • Data included pregnancies ending in live birth, stillbirth, or termination due to severe fetal anomaly between 1996 and 2006. SSRI exposure was defined as at least one purchase of an SSRI in the month before pregnancy or in the first trimester. SSRI-exposed women were less likely to be married than nonexposed women, twice as likely to smoke or to have a chronic medical condition, and 20 times more likely to have purchased other psychiatric medications. • Overall, after adjustment for confounders such as maternal age, diabetes, and purchase of other psychiatric drugs, major anomalies were not more common among the 6976 offspring exposed to SSRIs than among the 628,607 nonexposed offspring. In adjusted analyses, significant associations existed between fluoxetine and both overall cardiovascular anomalies (2.04% vs. 1.29% without SSRI exposure) and ventricular septal defects (1.43% vs. 0.87%); between paroxetine and right ventricular outflow defects (0.31% vs. 0.07%); and between citalopram and neural tube defects (0.29% vs. 0.09%). Prevalence of fetal alcohol spectrum disorders was higher with SSRI exposure than with no exposure (0.12% vs. 0.012%). • Comment: Even in this large, population-based study, anomalies were rare, making it difficult to reach definite conclusions. Still, the study gives further evidence of associations between SSRIs and at least cardiovascular anomalies, and clinicians must inform patients of these potential risks. Within the informed consent process, weighing these risks against those of untreated depression is essential. Clinicians should also address their patients' smoking and alcohol use and should avoid multiple psychiatric prescriptions during pregnancy.

12. A 2008 study in JAMA found that cancer patients who had end-of-life discussion with a health care professional were less likely to be:A) ResuscitatedB) On a ventilatorC) In the intensive care unitD) All the above

13. Answer • D) All the above

14. Which of the following is the more effective interview structure for eliciting patients' end-of-life concerns?A) Tell-ask-tellB) Ask-tell-ask

15. Answer • B) Ask-tell-ask

16. When interviewing a patient during an end-of-life conversation, it is recommended that the physician not allow more than 5 to 7 sec of silence between questions and responses.A) TrueB) False

17. Answer • B) False

18. Which of the following is not one of the criteria for a major depressive episode?A) Feeling of helplessnessB) Weight loss or gainC) AngerD) Decreased energy

19. Answer • C) Anger

20. Which of the following statements about depressive symptoms is true?A) Not considered the norm for terminally ill patientsB) Occur in the majority of patients receiving palliative careC) Occur in >75% of patients with advanced cancerD) None of the above

21. Answer • A) Not considered the norm for terminally ill patients

22. Depression is often _______ at the end of life.A) Overdiagnosed and overtreatedB) Underrecognized and under- or untreated

23. Answer • B) Underrecognized and under- or untreated

24. Which of the following is not considered a risk factor for depression at the end of life?A) Poorly controlled painB) Treatment with corticosteroidsC) Older ageD) History of substance abuse

25. Answer • C) Older age

26. All the following are characteristics of grief and not of depression, except:A) Focus on lossB) Having specific guilt or regretC) Emotions that come in wavesD) Preference for isolation

27. Answer • D) Preference for isolation

28. Choose the incorrect statement about dignity therapy for treatment of depression in patients receiving palliative care.A) Targets psychosocial and existential distressB) In a recent study, achieved high patient satisfaction ratingC) Shown to be effective in improving sense of dignity, but had no effect on depressive symptomsD) Shown to improve sense of purpose and meaning

29. Answer • C) Shown to be effective in improving sense of dignity, but had no effect on depressive symptoms

30. Which of the following statements about psychostimulant therapy for the treatment of depression in hospice patients is incorrect?A) Often poorly tolerated in this populationB) Has rapid effectC) Can counteract opioid-induced sedationD) May provide adjuvant analgesia

31. Answer • A) Often poorly tolerated in this population

32. The measurement of which of the following cardiac biomarkers is recommended as part of the early risk stratification of a patient with suspected acute coronary syndrome (ACS)?A) Creatine kinase-myocardial bandB) Brain natriuretic peptideC) Troponin I or TD) Myoglobin

33. Answer • C) Troponin I or T

34. The 2007 American College of Cardiology/American Heart Association (ACC/AHA) Class I recommendations for initial management and anti-ischemic therapy for ACS include all the following, except:A) Bed restB) Continuous electrocardiography (ECG) monitoringC) Intravenous (IV) nitroglycerineD) Supplemental oxygen (O2) in all patients

35. Answer • D) Supplemental oxygen (O2) in all patients

36. Which glycoprotein (GP) IIb/IIIa inhibitor is generally contraindicated as upstream therapy for ACS and indicated only if there is no delay in taking the patient to the cardiac catheterization laboratory?A) AbciximabB) EptifibatideC) Tirofiban

37. Answer • A) Abciximab

38. The antithrombotic agent _______is associated with a lower rate of bleeding but requires that patients be pretreated with clopidogrel.A) EnoxaparinB) FondaparinuxC) BivalrudinD) Unfractionated heparin

39. Answer • C) Bivalrudin

40. A conservative treatment strategy for ACS is recommended for:A) All men with low-risk featuresB) All women with low-risk featuresC) Almost all women, whether low or high risk

41. Answer • B) All women with low-risk features

42. There is a huge overlap of cholesterol levels in people with and without coronary heart disease (CHD).A) TrueB) False

43. Answer • A) True

44. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III 2004 update recommends a therapeutic goal of LDL<70 mg/dL for "very high risk patients," defined as those with:A) Established coronary artery disease plus multiple risk factorsB) Severe and poorly controlled risk factorsC) ACSD) All the above

45. Answer • D) All the above

46. In a recent cost analysis of lipid-lowering therapy, which statin regimen was found to achieve the greatest reduction in LDL?A) Atorvastatin 80 mg/dayB) Simvastatin 80 mg/dayC) Rosuvastatin 40 mg/dayD) Simvastatin 40 mg/day

47. Answer • C) Rosuvastatin 40 mg/day

48. Choose the incorrect statement about statin intolerance.A) Patient complaints about statins in clinical practice higher than reported in clinical trialsB) Muscle aches usually due to statin toxicityC) Rhabdomyolysis extremely rareD) True toxicity greater at higher doses

49. Answer • B) Muscle aches usually due to statin toxicity

50. After the starting dose, each time a patient's statin dose is doubled, it provides an additional _______ reduction in LDL.A) 3% to 4%B) 6%C) 10% to 12%D) 18%