Alan Lukazewski
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Homepage: http://www.elderdrugs.com
Posts by Alan Lukazewski
Patient Reporting of Suspected Adverse Drug Reactions: A Review of the Literature
Feb 17th
Published in the British Journal of Clinical Pharmacology in 2006 this article written by A. Blenkinsopp, and others, reviews the literature on patient-reported symptoms of suspected adverse drug reactions, also described as troublesome side-effects to medications that warrant medical attention. They included seven studies for review from seven different countries. Their conclusion was that patient reporting of suspected ADRs has more potential benefits than drawbacks.
Some of the more specific findings from the studies were: patient and healthcare professional reports are of similar quality; there was some evidence that different ADRs are reported; new ADRs are reported; reported symptoms to SSRI antidepressants, e.g. Zoloft, Celexa, Lexapro, Prozac, are not found in health care professional reports, implying a reluctance to report unusual psychiatric symptoms to physicians; some evidence that patients report ADR symptoms quicker; no evidence that reports result in distraction from signal detection, meaning they could distract from ADR signals and overload the ADR reporting system.
In all, patient-reporting of ADRs is a reliable method for detecting probable ADRs which can lead to mitigating them and improving quality of life, and avoid unnecessary utilization of health care resources, in addition to lessening the risk for patient harms. However, in my experience, if people are not educated on what side-effects to monitor for, and if physicians do not acknowledge that ADRs are possibly occurring, especially some of the more unusual ADRs, then a large percentage are not addressed and lead to negative outcomes. Several other studies have validated this finding. Lastly, specific questions asked of the patient that may elucidate and ADR is occurring should be included in every medication review and office visit. The reliability of this technique is greater than what one might think.
Hospital Readmissions within 30-days Associated with Adverse Drug Events
Feb 4th
Accountable Care Organizations (ACOs) may want to look a little deeper as to why many of their hospital patients who recently discharged are coming back within 30-days. An article in Annals of Internal Medicine, The Incidence and Severity of Adverse Events Affecting Patients after Discharge from the Hospital, Alan Forster, MD, et al, 2003;138:161-167, stated that 66% of the measured adverse events after discharge were adverse drug events. This point is also emphasized in a presentation by Dr. Steve Hines, PhD, and found on the AHRQ website (www.ahrq.gov/news/kt/red/readmissionslides/readmission.ppt). Dr. Hines also states possible causes of these adverse events that lead to harm and readmission, those being: poor transfer of information to the patient; poor transfer of information to the ambulatory caregivers, whether they be nursing homes, caregivers, or primary care physicians; and lack of a timely follow-up visit with the primary care physician, among others.
Looking deeper at the possible causes, Dr. Hines ascribes lack of medication reconciliation as one cause, where medications are not reconciled in detail which leads to duplicate drug therapies and drug interactions, thought to cause adverse drug events in about 26% of all ADE cases. He also states that patients may not ascribe adverse effects to medications and will not ask for changes in drug therapy. Yet a well-educated patient is more likely to recognize symptoms as an adverse event, implying that patient education upon discharge is critical. One possible solution is to create a comprehensive medication plan that travels with the patient after discharge so critical lab monitoring occurs, along with key educational points on how to properly take medication, in addition to a list of key symptoms that can be likened to the medication therapies the person is taking. Lastly, designing a drug regimen that the patient can adhere to is also important, especially for people discharged after an episode for congestive heart failure. Poor adherence is strongly associated with readmission to the hospital in those with congestive heart failure.
In summary, medications play a key role in mitigating risk and improving survival and function, but when not well managed they can lead to adverse drug events that cause harm and lead to readmission to the hospital. Some data suggest that the adverse events will show up about 14 to 21 days after hospital discharge implying that a well-designed medication plan can prevent a large number of readmissions.
Here are some other links that refer to adverse drug events after discharge from hospitals.
http://bennet.senate.gov/newsroom/press/release/?id=3d5c9532-be2a-4a3f-baa9-3f9196d394aa
Adverse Drug Reactions in Older Veterans
Jan 29th
An article published recently in the Journal of the American Geriatrics Society titled Prevalence of Unplanned Hospitalizations Caused by Adverse Drug Reactions in Older Veterans; Zachary Marcum, et al, Jan. 2012, concluded that the number of medications a person takes is an independent risk factor for experiencing an adverse drug reaction (ADR). The calculated odds ratio for 5 to 8 medications was 2.85 and for >8 medications 3.90, which implies a high degree of correlation. The most common ADRs were bradycardia (slowed heart rate) from beta-blockers (atenolol, metoprolol, etc.) and digoxin; hypoglycemia (low blood sugar); falls associated with antidepressants and ACE inhibitors (lisinopril, enalapril, etc.); and mental status changes from anticonvulsants and benzodiazepines (lorazepam, alprazolam, etc.).
These findings are consistent with a large body of literature that the greater the number of medications we take, the greater the risk or likelihood we will experience an adverse drug reaction that causes us to seek medical attention. Using the number of medications a person takes as a screening tool should prompt all parties involved to review a persons medications to: ensure they are needed, that the doses are appropriate,that monitoring is in place, are free from significant drug interactions, and taken properly, since all of these contribute to the risk for an adverse drug reaction.
In the discussion section, the authors go on to talk about the concept of medication-minimization and how this approach might lead to a lower rate of adverse drug events, albeit how it can be a challenging task to pare down a complicated drug regimen. However, there is a growing body of evidence that suggests how we can pare down the drug regimens of an older adults without causing harm, and in many instances improve how they function. This is an area that will gain greater clarity in everyday practice and drastically change medication utilization in older adults, all for the greater good.
Stroke Risk Increases Risk for Memory Loss
Jan 19th
A recent study in Neurology found a link between the risk of having a stroke and future development of memory loss or cognitive decline. The link was strongly tied to high blood pressure. The study, called REGARDS, involved 23, 752 older adults, average age 64, and followed them for 4 years. In those with a higher risk of stroke at the start of the study they had a higher incidence of cognitive issues. For every 10mmHg increase in systolic blood pressure (the upper number) there was a 4.1% increase in the risk of developing cognitive issues.
The upper number of blood pressure, also called systolic, is very important in older adults as it tends to rise with age, which was another risk factor from this study that was correlated with stroke risk. In my experience with helping older adults it is common to find isolated systolic hypertension, occurring in about 30% over the age of 80. Isolated systolic hypertension is where the upper number is elevated but the lower (diastolic) number is normal. Treatment of this type of high blood pressure is very effective at preventing strokes in which only 13-18 people need to be treated to prevent one stroke. What is also important to note is that “silent strokes”, in which you have very small strokes that go undetectable but contribute to cognitive decline, can be reduced by better management of your high blood pressure.
My advice, pay attention to your blood pressure and if that upper number is higher than 140, see your doctor and start a conversation. Also keep in mind that self-monitoring of your blood pressure and sharing those recordings with your doctor is more likely to catch high blood pressure, and is also known to be more accurate than the occasional blood pressure check in the doctor’s office.
Patient Reported Symptoms from Crestor
Jan 19th
Here’s a link from AskAPatient.com, a consumer-based website that allows people to post what they believe are side-effects from their medications. Although there is no validation that reported side-effects are always from the medication, there is usually a trend that can be followed along with some activity by the person helping to point the finger of suspicion at a particular medication. One way to strengthen an argument that a medication is responsible for a life-altering side-effect is to stop it, and then monitor how you feel and function. This report is on Crestor, not that I’m picking on Crestor, but it speaks well to how the medication is most likely responsible for such severe pain that it prevented this 86 year old women from being able to care for herself. In the final analysis, one would want to consider restarting the Crestor and see if the same side-effect returns. If it does, then we have further strengthened the argument that the drug is responsible. These reports also strengthen the argument that people with changes in how they feel and function, especially after starting a new medication, should report them to their physician and not take no for an answer until there has been a rigorous process to verify if the medication may be responsible. A simple shrug of the shoulders or a “I think not” reply should not suffice.
http://www.askapatient.com/viewrating.asp?drug=21366&name=CRESTOR
The Risk of Determining Risk with Multivariable Models
Jan 12th
Here is an article that reviews the use of statistical applications for determining risk which proves there is a significant misuse of statistics in the medical literature thereby leading to inaccurate conclusions. The importance of this subject matter can not be overstated since there is an abundance of published studies in which practitioners take the authors conclusions for granted and apply those conclusions to their daily practice, yet the stated conclusions may be false.
My quest for a solid explanation started some time ago when reported findings from a couple studies made no sense at all, and I read the statements of “..after adjusting for confounding variables or risk factors..”. I first verified my suspicion in Dr. James DeMuth’s book on pharmaceutical statistics where he states we can not adjust for confounding variables and assume the conclusion is a direct cause and effect. All we can state is a correlation exists, but some authors seem to go much farther in drawing conclusions. In this article, by Dr. John Concato, et al, published in Annals of Internal Medicine, 1993;118:201-210, the author reviews common problems with the use of multivariable analyses, the first being the over-fitting of data, in which too few sample outcomes are applied to a model, and then correlations drawn from those too few outcomes. Other problems involve non-conformity to a linear gradient. For example, the impact of left ventricular ejection fraction on negative outcomes not being linear and is dependent upon where the initial ejection fraction was measured at baseline, e.g. a reduction from 40% to 30% has much lower risk as compared to a reduction from 25% to 15%.
Another problem is what the author says is a “violation of proportional hazards”, in which the risk or hazard of an independent variable is assumed to be constantly proportional. This false assumption is probably where I became suspicious, that a simple “adjusting for confounding variables” assumes all variables to be constant and exist in a simple relationship of direct correlation. The main point I make is that many statistical analyses have limitations and become more limited in their usefulness when they are not applied correctly thereby leading to incorrect conclusions.
Isn’t it true, that on any given day, we can read the summary of a research article which states that a treatment is associated with a negative outcome, after having adjusted for confounding factors, etc. And then one month later we read the opposite results from another study. It begs the question, which article is most accurate in their conclusions, if either? The use of statistics in medical research has accelerated in the last twenty years but not without concerns over the quality of its applications. I, like most human beings, tend to take things at face value. But as more findings hit the news I find myself having to employ discipline and not form any opinion until a detailed analysis of the study can be made to determine if, in fact, the purported conclusions have any meaning at all. The other application of this principle is for the lay person, no matter how educated, do not react to any information in the news.
Trusting What Your Patients Tell You: Detecting Adverse Events in the Office Setting
Dec 30th
There are several published articles that have caught my attention that focus on perceived and self-reported adverse events in the patient population. One article, Adverse Drug Reactions in Elderly Patients as Contributing Factor for Hospital Admission: cross sectional study, Mannesse, C., et al, BMJ Vol 315, Oct. 1997. They reported that people were reliable in detecting adverse drug events in themselves, with a correct opinion in 73 out of 93 who answered the question whether they were experiencing an adverse drug event (ADE). However, these were adverse events that were less severe, and the more serious adverse events that caused hospitalization, such as gastrointestinal bleeding, were not well detected. In another study, Patient-reported Medication Symptoms in Primary Care, Weingart, S, MD, et al, ArchIntMed, Vol 165, Jan. 24, 2005, the authors measured how many people thought they were experiencing an adverse event (179 people & 286 events) and what percentage reported them to their physicians, along with what percentage were acted upon by their physicians. Only 69% were reported to their physicians, and only 76% were acted upon. The authors estimated that a failure to report symptoms led to 19 (21%) ameliorable ADEs, and 2(2%) preventable. A failure to change therapy in 48 cases led to 31 (65%) ADEs that authors estimated to be ameliorable. The conclusion is that people are fairly good at knowing when they are experiencing and ADE, a lesson I learned early on in working with older adults in a retirement community, where an older adult convinced me he was experiencing memory loss from one of his medications, but I didn’t believe him at first. So if we listen and believe, kind of like having faith, we should be able to detect an ADE before it affects the function of the older adult. We just need to ask the question.
In a study in progress, we performed comprehensive medication reviews (CMRs) in 69 older adults and within the CMR questionnaire we asked the two questions, 1) What history do you have of adverse drug events (medication side-effects)?, and 2) Do you think you are experiencing an adverse drug event right now? Of the 69 participants, 28 answered both questions positive, yet only 4 said they were having an ADE but had a negative history of an ADE. When applying a 2×2 contingency table with Fischer’s test for exactness, we found a p-value of 0.00001 meaning the correlation was highly significant. That is to say, people were far more likely to say they are experiencing an ADE if they had a history of an ADE, as opposed to those without a history. This aligns with another article titled Adverse Drug Reaction Risk factors in Older Populations, Hajjar, E., Hanlon, JT, et al, AmJGerPharm., Dec. 2003 Vol. 1 (2) 82-89. Risk factors for ADEs were developed by a panel of experts in ADEs and one risk factor identified and agreed upon by the experts was a history of an ADE.
So it stands that it might be wise to put in your office visit routine the questions of “What history of adverse effects do you have from medications?” and “Do you think you are experiencing an adverse effect right now?”, and then listen and act. You might positively affect the life of an older adult by keeping them more functional and/or out of the hospital.
Emergency Hospitalizations for Adverse Drug Events in Older Americans
Dec 20th
A study published recently in the New England Journal of Medicine, by Dr. Daniel Budnitz, et al, states that there are just a few drugs commonly used in older adults that lead to emergency hospitalizations, those drugs being: warfarin (Coumadin), insulin, oral antiplatelets and oral hypoglycemic agents like glipizide and glyburide. These findings are similar to a study Dr. Budnitz published in Annals of Internal Medicine in December 2007 in which these classes of medications were implicated in emergency department visits for ADEs. These two studies do state very well that if we focus on just a few key drugs we can prevent a large percentage of ADEs in older adults that lead to ER visits and/or hospitalization.
In the more recent study, increasing age, number of medications and these four classes of drugs were most strongly associated with ADEs leading to emergency hospitalizations. Other medication categories that were involved in a large number of emergency hospitalizations were: cardiovascular drugs, antibiotics, sedative hypnotics, anticonvulsants, opioid analgesics, and Beer’s list medications. When factoring digoxin out of the Beer’s list admissions the percentage of admissions from Beer’s list drugs dropped nearly in half. It was also interesting that in 47% of cases the dose of digoxin was appropriate, according to Beer’s criteria. This means the dose of digoxin alone is not a completely effective screening criterion, but perhaps more frequent monitoring and drug interactions may play a role.
Speaking of drug interactions, this study did not report on the role that drug interactions have in leading to ADEs in older adults. There are recent data that list just a few critical drug interactions that lead to emergency room visits and hospitalizations in older adults. You can learn about those drug interactions at my post: http://elderdrugs.com/2010/11/adding-a-new-medication-watch-out-for-these-drug-interactions/
With regard to the anti-diabetic medications insulin and oral hypoglycemics, the implication is strong that routine monitoring and engagement of the person with diabetes is critical in catching downward trends of blood glucose in order to prevent severe hypoglycemia from occurring. As a diabetes educator I have always preached that the person with diabetes who is actively engaged in their own health is more likely to be successful, as opposed to the person who does not take an active role in managing their diabetes.
In conclusion, this study confirms previous studies and the role that just a few medication classes play in causing a large percentage of ER visits and hospitalizations in older adults. However, we mustn’t forget the large percentage of ADEs that lead to functional or cognitive impairment that we may just “chalk up” to aging. With the aging body less able to tolerate the insult from multiple medications, and with so many possible ADEs that can occur in those with complex medication regimens, anything less than a comprehensive medication review and development of a structured medication plan will fall short of the goal. So I advise to look at the entire body of literature and make your comprehensive medication review checklist in order to not miss some key contributors to ADEs in the older adult.
Are You Using a Medication to Treat a Side-Effect and Don’t Know It?
Dec 10th
When reviewing medications of an older adult it is not unlikely that some of the medications could have been prescribed to treat side-effects from other medications. This is called a “prescribing cascaded”. Some examples of prescribing cascades are:
- Starting a bladder health drug such as Detrol (tolterodine), Ditropan (oxybutynin), Vesicare (solifenacin) or other, in someone who develops urinary incontinence from Aricept (donepezil), Exelon (rivastigmine) or Razadyne (galantamine). In one study it was shown that people who used this class of memory health drugs were 1.5 times more likely to be prescribed a bladder health agent. The bladder health agent may also lessen the beneficial effects of the memory health drug.
- NSAIDs such as ibuprofen, naproxen, among many others, causing high blood pressure from the effects of the NSAID on the kidneys. What can follow is the addition of a medication for high blood pressure.
- The addition of a diuretic due to the development of fluid retention from a medication for high blood pressure such as amlodipine (Norvasc).
- The development of joint pain from a bone health drug such as Fosamax (alendronate), Actonel (risedronate) or Boniva (ibandronate), and then an analgesic or pain medication is added, which can then lead to side-effects depending upon the type of pain medication started. This prescribing cascade was validated by FDA and alerts were posted in 2008 and 2009.
- One last example is the use of Reglan (metoclopramide) for nausea, which then leads to the side-effect of movement disorders that mimic Parkinson’s disease. Those that present with this Parkinson’s-like side-effect are more likely to be misdiagnosed with Parkinson’s disease and treated with more medications to manage the tremors or slowness in movement that are the side-effects from the metoclopramide.
A key point to keep in mind is that you should always look back to when a medication was started to see if the side-effect, which is being treated as a condition or disease, followed not long after the addition of the primary drug. This is trying to develop a “temporal association” or an association related to the time of starting a new drug and the appearance of a side-effect. This leads to the primary principle in geriatric pharmacy management and that is “Always suspect the drug until proven otherwise”. If you can spot prescribing cascades it may be possible to reduce unnecessary medications that lead to adverse effects. Check with your doctor of pharmacist if you suspect a side-effect from a drug that may be treated with another drug. There is a good article that lists other prescribing cascades and speaks to the concepts more in depth at: http://www.australianprescriber.com/magazine/34/6/162/6
Comparative Effectiveness of Medication Adherence Interventions
Dec 8th
The Agency for Healthcare Research and Quality (AHRQ) has posted their comparative effectiveness review of medication adherence interventions. This can be useful for pharmacists and case managers. Here’s the link: http://www.effectivehealthcare.ahrq.gov/ehc/products/296/877/Medication-Adherence_Draft-Report_20111206.pdf
