Adverse Drug Events

(2/6/14)- The official Food and Drug Administration’s site to report and get info on adverse drug reactions is fda.gov/safety. The following is a quotation dealing with adverse events that take place in hospitals:

“What Is Known About Adverse Events in Older Medical Hospital Inpatients?
A Systematic Review of the Literature
Susannah Jane Long, Katrina Fiona Brown, Diane Ames, Charles Vincent Disclosures
Int J Qual Health Care. 2013;25(5):542-554.

Large international studies have shown that older hospital inpatients are at particular risk of adverse events. The purpose of this review was to synthesize data from studies designed to assess the scale and nature of this harm, with the ultimate aim of informing the development of new safety and quality measurement tools to facilitate improved hospital care for these vulnerable patients.

A systematic search using Ovid SP and other sources was carried out, rigorous inclusion and exclusion criteria were applied and quality assessment of included studies was conducted. Data were synthesized to give a picture of the incidence, types, causes, preventability and outcomes of adverse events in older medical inpatients.

Results of data synthesis Nine relevant studies were identified. A wide range of adverse event incidences were reported, from 5.29 to 6.2% in re-analyses of large adverse event studies, to 60% in studies in which the development of 'geriatric syndromes' (e.g. falls, delirium, incontinence) was also considered to be adverse events. Important causative factors other than age included clinical complexity, co-morbidity, illness severity, reduced functional ability and lower quality of care. Adverse events in older people lead to unnecessary interventions with resultant complications and increased length of stay.

Conclusion More work is needed to understand the complex nature of adverse events in older inpatients. We must tailor safety measurement and improvement strategies to address challenges presented by the complexity of the geriatric syndromes and the processes of care encountered by older inpatients.”

(2//10/12)- Starting in September of last year, AdverseEvents Inc. has streamlined the FDA's database of adverse events reports so that consumers can search online, at no cost, adverse event reports on over 4,500 drugs that were filed with the agency. That site can be found at adverse events.com

AdverseEvents Inc. developed an algorithm that filters out duplicates and combines spelling variations, reducing over 200,000 drug names to about 4,500. Its database goes back to 2004.

(11/7/10)-This comes from The Kaiser Health News Morning Edition:

"Hospital admissions for adverse reactions from medications and illegal drugs doubled ... between 1997 and 2008, according to a new government report,

"The report, released by the Department of Health and Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ) found that there was a major increase in hospital discharges from effects of both prescription and over-the-counter medications, as well as illegal drugs, among adults ages 45 and older.

The increase was largely driven by hospitalizations from conditions related to three types of medications and drug-related conditions: drug-induced delirium; 'poisoning' or overdose by codeine and other opiate-based pain medicines; and withdrawal from narcotic or non-narcotic drugs, according to the press release .

(12/30/02)-Adverse drug interactions are increasing and are unfortunately more serious because more drugs and drug combinations are being prescribed than ever. According to the National Center for Health Statistics, doctors wrote at least one prescription in 64% of their patient's visits in 2000. For the year 2000, American doctors wrote a total of 2.8 billion prescriptions, an average of 10 per person.

The Institute of Medicine reported that in 2000, there were about 100,000 deaths due to medical errors of which about 7,000 were attributed to drug reactions. Not all drug reactions can be foreseen, in part due to the fact that new medications are approved after being tested on an average of 3,000 people over a relatively short period of time. Hopefully modern science is coming up with some help in this area as new software is being developed, and is now available that can help prevent these adverse drug interactions.

Sometimes however it is not only drug interactions that can cause the problem. A patient may fail to tell a doctor about his or her usage of herbaceuticals and dietary supplements. This can be a fatal error because natural remedies are biologically potent and can interact strongly with a prescription drug.

There was an article written in Family Practice Recertification (2002; 24(7): 65-71) which described rules for avoiding adverse drug reactions and interactions in geriatric depression. In the article the authors stated "While it is unclear whether the elderly are more likely to develop depression than younger adults, depression following hospitalization and related comorbid illnesses such as myocardial infarction, stoke, malignancy, and Parkinson’s disease are undoubtedly more common in older patients." The authors, Drs. Jack D. McCue and Steven M. Krause refer to the Olfson et al article in JAMA 2002; 287:203-209, a review of outpatient treatment trends in depression. One table in the McCue & Krause article lists the medications associated with depressive symptoms, adapted from Goldberg RJ. Depression in hospital medicine. Hosp. Med. 2001; 2:1-10, which we reprint below:

Medications associated with depressive symptoms

Acyclovir (Zovirax)	Estrogens
Alcohol	Haloperidol (Haldol)
Amantadine HCL (Symmetral)	Hydralazine HCL (Hydra-Zide)
Anabolic Steroids	Interferon
Anticholinergics	Levodopa
Anticonvulsants	Methyldopa (Aldomet
Antidepressants (withdrawal)	Metronidazole (Flagyl)
Baclofen	Narcotics
Benzodiaepine	Pergolide mesylate (Permax)
Cancer chemotherapy	Propanolol HCL (inderal, inderide)
Choral hydrate	Ranitidine HCL (Zantac)
Cimetidine HCL (Tagament)	Reserpine
Clonidine (Catapres)	Sedatives
Corticosteroids	Thiazides
Cycloserine (Sermycin)	Thiothixene (Navane)
Dapsone

We think our readers need to be aware of three points made by McCue and Krause, which we quote at length:

"…since clinicians are unable to predict reliably whether a patient will have a better therapeutic response to a particular class of antidepressants or to individual drugs within each class, empiric therapeutic choices should be rationally based on other factors whenever possible. Safety, tolerability, ease of dosing, and potentially troublesome drug-drug interactions should be important considerations." 

"…since one can anticipate that about one third of patients will not respond to the initial dose, but may respond to a second or third drug, clinicians should be familiar with several antidepressants." 

"…when treating elderly, it is necessary to be cognizant of the problem created by chronic disease comorbidity and polypharmacy (and resultant "patient fatigue" with multiple empiric trials), and to prescribe drugs with the most favorable side-effect profile."

They conclude their article with the following caveat that would seem to make the most sense in any medication treatment protocol:

"PATIENTS AND PHYSICIANS CAN HELP IMPROVE THE SAFETY OF MEDICAL TREATMENT OF DEPRESSION BY ESPOUSING THERAPEUTIC PARSIMONY AND SIMPLIFYING DRUG REGIMENS."

An ongoing review of the literature consistently alerts the reader to examples of problems with medication delivery. A research study by Bruce and Wang looked at the error rate during administration of parenteral medication by nursing staff in a hospital setting.

During emergencies, parenteral administered medications are preferred because oral medications may be poorly absorbed and not provide as rapid response as needed. This study used a direct, disguised observational method in an admission unit during daylight hours (8:00 AM to 4:30 PM) for 4 weeks. Any error observed that was potentially dangerous to the patient was either stopped or corrected immediately. Ethical considerations were not compromised. It is well reported that poorly prepared and/or administered parenteral therapy can cause thrombus formation, severe hypersensitivity reactions and infections.

In a total of 127 opportunities for error, 27 errors were observed (25% error rate) which included wrong time errors (medication administered one hour over the prescribed time). If one removes these types of errors, the rate of errors was reduced to 10.7%. The researchers conclusion was that parenteral medication administrations errors are common in the United Kingdom. This does not necessarily mean that the same results would found in the United States, but it is still disquieting especially when one looks at nursing homes and the demands made on nursing staff.

In this era of the unbelievable, we must add this story seen on TV. CNN TV has made us aware of a gross surgical error in which the surgical team left a 13-inch retractor inside an individual following an operation. This was only discovered after a period of intense suffering by the individual and experiencing difficulty passing through the electronic surveillance at an airport.

The United States has in place an elaborate system to balance risks and benefits of medications dispensed by physicians. The system helps promote a process of pharmaceutical development, testing, manufacturing, labeling, prescribing, and dispensing in ways that are supposed to maximize benefit and reduce risk.

Overseeing this system is the Food and Drug Administration. The Food and Drug Administration has a pre-marketing procedure for evaluating the safety, efficacy and approval process, as well as a post-marketing surveillance program of every drug. In recent years, because of concern by patient groups to get useful drugs to the market at a faster rate, an advanced drug review process, it is important for the FDA to enhance its post-marketing surveillance to identify risk factors associated with the use of the drug.

How prevalent are these adverse drug effects? The following table appeared in the Philadelphia Inquirer, 11/12/01 that compiled and extrapolated rate of death data from various sources.

Deaths in past 5 weeks*

Cause of death	Number
Smoking-related	38,462
Flu-related	6,124
Auto accidents	4,080
Alcohol-induced	1,835
Murders	1,618
AIDS	1,412
Medication errors	673
Airplane crashes*	269
Firearm accidents	80
Lightning strikes	7
Anthrax	4
West Nile virus	0.19
Shark attacks	0.09

• Does not include recent airplane crash in NYC.

In 1999, the Institute of Medicine (IOM) published a report, To Err is Human, which indicated anywhere from 44,000 t0 98,000 deaths around the world due to medical error and suggested that 75 percent to 80 percent of these deaths are caused by hospital acquired, or nosocomial, infections. The National Patient Safety Benchmarking Center is a data repository of adverse events culled from various hospitals and 300,000 patients and this data has been analyzed by SafeCare Systems of Boston. Indications are that adverse events cost $2.5 million to $4 million/100 beds per year. The following table presents a breakdown of the most frequent medical errors and adverse events and the percentage of total costs.

Most Frequent Medical Errors/Adverse Events and Their Costs

Error/Event	Top five contributors to frequency (percent of total)	Top five contributors to cost (percent of total)
Surgery	20	31
Medication errors	16	11.7
Medical errors (nonsurgical)	14.8	16.6
Patient falls	8.8
Pressure ulcers		8.3
Nosocomial infections	7.5	13.8

 Surveillance systems rely on manufacturers, the health care delivery system, individual providers, and patients for data. Regrettably, the comprehensive system lacks the integration needed to ensure optimal public health and safety. Someone has to notify the FDA about the adverse effect of the medication.

There is a form to be filled out by either physician or consumer and returned to the FDA, the UPS or the Institute for Safe Medical Practices. In the United States, medication errors should be reported to the USP Medications Error Reporting Program at 800 23 ERROR or by completing a reporting form available through USP. You may also report through the Internet at www.usp.org complicating the issue of adverse drug effects is the use of polypharmacy and over-the-counter drugs and herbal supplements that may have synergistic effects on prescribed medications.

The issue of drug names also can cause confusion and potential adverse effects. For example, Janssen has changed the package label appearance for ACIPHEX (rabeprazole sodium) to help differentiate it from ARICEPT (donepezil), one of their other products. This confusion can be the result of difficulty in reading the prescription. Worse, prescription errors are blamed for 7,000 deaths a year. Among the causes are illegible prescriptions and slipups by pharmacists.

Answers to the handwriting problem may lie in computer technology where doctors can print out a prescription. An interesting twist on this is being introduced in the state of Minnesota. InstyMeds is the first automated prescription drug dispenser to hit a doctor's office, the latest in a trend toward computerizing prescriptions to cut not just drugstore lines but dangerous errors.

The physician types into the machine the patients weight as well as other demographic data. The machine then figures out the proper dosage and provides a prescription printout and a security code. The patient then types in the security code. The computer verifies the prescription as well as checks insurance records to determine amount of coverage. The patient uses his/her credit card to pay for the medication. The machine dispenses the right dose and amount, with an instruction label and pertinent information.

So far, InstyMeds is a pilot project. But Minnesota's pharmacy regulators just approved its use anywhere in the state, and the inventor, a practicing pediatrician, hopes eventually to place the dispensers in doctors' offices and emergency rooms around the country. If it works, it should prove a valuable tool in reducing drug adverse effects.

The downside is that poor individuals, those who do not have a credit card, could not use this machine and there would be no friendly pharmacist to answer questions the patient may have about the medication. Could the automated prescription drug dispenser stock the range of medicines prescribed by the physician? The present prototype machine stocks 80 different medications.

Drug companies have an invested interest (in psychology it is called determining tendency or "halo effect") in believing the medication works, despite the occurrence of potentially adverse effects. Similar situations exist in other industries. The tobacco and tire industry appeared to hold back information that implicated their product in severe adverse effects. Should we place total responsibility on the industry to monitor their products or should an independent organization maintain an arms length distance and do the monitoring?

Experts estimate that millions of adverse events associated with medical products and drugs occur each year. Some of these adverse events result in the death of individuals. Lazarou et al reported in 1998 that the incidence of serious and fatal adverse drug reactions in hospitalized patients is very high. In a review of 39 prospective studies, the researchers estimated a 6.7% overall incidence of serious adverse drug reactions for hospitalized patients.

This translates into one of every 15 patients in a hospital suffering from a serious adverse drug reaction. According to Kohn et al, an estimated 45,000 deaths per year occur as result of medical errors in US. One of the major elements of medical errors outlined in the Kohn book was medication error, consisting of prescribing errors, dispensing errors and administrative errors.

Buajordet et al., as result of their review of fatal adverse events, suggest, "A systematic strategy is needed to avoid unnecessary adverse drug events." The study showed a high incidence of the adverse events was associated with age, high comorbidity and polypharmacy and partly to inappropriate drug prescribing or use. They point out the following treatments as conducive to fatal drug reactions: bronchodilatory treatment of outpatients with both chronic obstructive pulmonary disease and coronary heart failure; vasodilatory treatment in patients with endstage heart failure; the combination of several antithrombic drugs.

Response to a drug is determined by its pharmacological profile, the individual characteristics of the patient, and the way the drug is prescribed. Medicine and dose selection for the elderly are complicated by the greater frequency of decreased hepatic, renal or cardiac function and concomitant diseases found in this age group. Changes in the digestive system, proportion of fat and circulating total body water may also alter the volume of distribution of medications.

Information on drug safety, especially long-term safety, is often limited. Post-marketing drug surveillance is an essential component of determining the true risk profile of a drug. Information through this surveillance mechanism is obtained in Phase IV studies that provide long-term safety data.

But who would sponsor such a study? The pharmaceutical companies who have an invested interest in seeing a return on the monies they spent to develop the drug? Bayer withdrew its Baycol brand of cerivastatin on August 8, 2001 when it was discovered that it might cause a potentially fatal muscle-wasting side effect in some patients. Interestingly, this has prompted calls by European Union drug authorities for a reexamination of the safety of the whole "statin" class of drugs. Does it take a serious untoward incidence to monitor the clinical effectiveness of medication that patients are taking under the presumed assumption that it can help deal with the disease they brought to the attention of their treating physician?

Sources of unintended outcomes from adverse events fall into four categories: (1) product defects, (2) known side effects, (3) medication or device errors, and (4) remaining uncertainties. Many factors contribute to increased risk. The growing complexity of medical technology, economic pressures, and frequent organizational changes in health care institutions increase the potential for unanticipated or unintended outcomes. Not all the errors may be related to the drug per se. They may be the result of administering the wrong medication or mixing up medications due to the similarity in the name of the drug. .

Consequently, post-marketing surveillance must change from a passive system to one that is proactive in its strategy. The new strategy must examine organizations' use of medical devices, the way problems are perceived and reported, and the range of factors that contribute to any adverse event.

The FDA, in an effort to improve the system, is making significant outreach efforts to stakeholders to solicit their ideas, opinions, and concerns. Consumers need to be aware of potential adverse effects of medications and report them not only to their primary physician but also to the appropriate authorities. What is ultimately needed is proactive tools that improve care delivery significantly through vastly enhanced automation of the clinical process. We will continue to report on this issue with the goal of the powers to be setting up strict standards to avoid such adverse events.

References mentioned in this article.

J. Bruce & I. Wong. Parenteral Drug Administrations Errors by Nursing Staff on an Acute Medical Admission ward during the day. Drug Safety 2001; 24(11): 855-862.

Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta analysis of prospective studies. JAMA 1998; 279:1200-1205.

Kohn LT, Corrigan JM, Donaldson MS. Eds. To err is Human: Building a Safer Health System. Institute of Medicine Washington DC: Natianal Academny Press 2000.

Buajordet I, Ebbesen J, Erikkesen J, Brers O, Hilberg T. Fatal Adverse Drug Events: the paradox of drug tratment. J. Inter. Med 2001; 250:327-341.

FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE
" How to Select a Nursing Home"

Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated February 6, 2014

http://www.therubins.com or allanrubin4@gmail.com

e-mail: hrubin12@nyc.rr or

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