To test the hypothesis that non–steroidal anti–inflammatory drugs (NSAIDs) accelerate the progression of osteoarthritis by reducing synthesis of vasodilator prostaglandins, thereby diminishing joint perfusion, 105 osteoarthritis patients awaiting hip arthroplasty were treated prospectively with a strong or weak prostaglandin synthesis inhibitor, indomethacin or azapropazone, respectively. Pain and radiological joint space were monitored during the period up to arthroplasty and the condition of the excised femoral head was determined. As judged by radiological and histopathological data, the two treatment groups were at a similar pathophysiological end-point when they came to arthroplasty. In the indomethacin group the affected hips lost joint space more rapidly than did the contralateral hips, a difference not seen in the azapropazone group. The patients receiving azapropazone, who had higher concentrations of synovial vasodilator prostaglandins, took longer than the indomethacin group to reach the arthroplasty end-point. Potent inhibitors of prostaglandin synthesis may be inappropriate in the management of osteoarthritis of the hip.
Cartilage Maintenance in Osteoarthritis: Interaction of Cytokines, NSAID and Prostaglandins in Articular Cartilage Damage and Repair
The structural integrity of the matrix of human articular cartilage is maintained by a dynamic equilibrium between synthesis and degradation. In osteoarthritis (OA), synthesis may be inhibited by the presence of subnanogram quantities of the cytokine interleukin 1 (IL-1), leading in the longterm to loss of matrix and susceptibility to mechanical damage. IL-1 may also inhibit the potential for repair processes to take place in this cartilage if continued synthesis and secretion of the cytokine occurs. Evidence is presented that animal and human cartilages are sensitive to the action of certain nonsteroidal antiinflammatory drugs (NSAID) in inhibiting the synthesis of cartilage proteoglycan and also diminishing the repair activity of cartilage recovering after IL-1. In OA cartilage, the sensitivity to action of NSAID may depend on the state of the tissue in terms of glycosaminoglycan (GAG) turnover and GAG synthetic activity of the indigenous chondrocytes. Preliminary investigations of the prostaglandin analog misoprostol on the synthetic repair activities of animal and human cartilage in the presence of NSAID are reported.
The best evidence indicates that cervical manipulation for neck pain is much safer than the use of NSAIDs, by as much as a factor of several hundred times. There is no evidence that indicates NSAID use is any more effective than cervical manipulation for neck pain.
There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.
Prescribing of Nonsteroidal Anti-inflammatory Drugs in General Practice: Determinants and Consequences
The data are compatible with 1 hospital admission per 2823 NSAID prescriptions (95% confidence intervals 2098-8110) and they emphasize the need for strategies to reduce levels of NSAID prescribing.
We compiled reports of acetaminophen hepatotoxicity after multiple overdoses from published cases, cases reported to the Food and Drug Administration, and cases from Children’s Hospital Medical Center, Cincinnati, Ohio. Forty-seven children (age range, 5 weeks to 10 years) received 60 to 420 mg/kg/day for 1 to 42 days; 52% had received adult preparations of acetaminophen. The mean peak serum aspartate aminotransferase level was 10,225 IU/L (n = 45), and the mean serum alanine aminotransferase level was 7355 IU/L (n = 31), which were significantly higher (both p < 0.001) than the mean serum aspartate aminotransferase level of 3500 IU/L and alanine aminotransferase level of 3098 IU/L found in children (n = 12) with non-acetaminophen-associated hepatic failure. Serum acetaminophen levels for which an estimate of time from last dose could be calculated were available for 30 patients, of which 22 levels were greater than the toxic range described for acute ingestion. Twenty-four of 43 patients (55%) died, with an additional three surviving after orthotopic liver transplantation. Parents should be advised about the potential hepatotoxicity of acetaminophen when given to ill children in doses exceeding weight-based recommendations.
Incidence of Adverse Drug Reactions in Hospitalized Patients – A Meta-analysis of Prospective Studies
The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.
Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated.
Starting in the early 1970s, numerous new NSAIDs were developed that were initially believed to be devoid of gastrointestinal toxicity, but few, if any, are entirely harmless. These agents constitute one of the most widely used classes of drugs, with more than 70 million prescriptions and more than 30 billion over-the-counter tablets sold annually in the United States.  Although NSAIDs are generally well tolerated, adverse gastrointestinal events occur in a small but important percentage of patients, resulting in substantial morbidity and mortality.
A Comparison of Iatrogenic Injury Studies in Australia and the USA. II: Reviewer Behaviour and Quality of Care
A similar 2% core of serious AEs was found in both studies, but for the remaining categories six to seven times more AEs were reported in QAHCS than in UTCOS. We hypothesize that this disparity is due to different thresholds for admission and discharge and to a greater degree of under-reporting of certain types of problems as AEs by UTCOS than QAHCS reviewers. The biases identified were consistent with, and appropriate for, the quite different aims of each study. No definitive difference in quality of care was identified by these analyses or a literature review.
Perioperative Deaths: A Further Comparative Review of Coroner’s Autopsies with Particular Reference to the Occurrence of Fatal Iatrogenic Injury
There appears to have been a steady increase in the number of perioperative deaths reported to the Coroner over the previous triennia (1989 to 1997) for which autopsies were conducted. While this observation may not denote an increase in perioperative morality rates per se, it may be indicative of an increasingly “aggressive” or defensive approach to the clinical management of seriously ill patients, particularly over the past decade. Although the rate of iatrogenic deaths appears to have stabilised, it is too early to say whether this apparent trend will persist in the future. It is perhaps not surprising that the risk of iatrogenic injury appears to increase with the number of interventions performed; however, it is not clear why initial, supposedly elective, interventions should be associated with an apparently greater risk of iatrogenic injury than those classified as emergency procedures. The substantial divergence between the autopsy finding of an iatrogenic death and the corresponding Coroner’s verdict of misadventure may be comforting to clinicians, but certainly warrants further examination.
Medication errors were common (nearly 1 of every 5 doses in the typical hospital and skilled nursing facility). The percentage of errors rated potentially harmful was 7%, or more than 40 per day in a typical 300-patient facility. The problem of defective medication administration systems, although varied, is widespread.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for musculoskeletal injuries because the conditions are believed to be inflammatory in nature. However, because inflammation is a necessary component in the healing process, decreasing inflammation may prove counterproductive. Also, many tendon injuries called ‘tendinitis’ are, in fact, degenerative and not inflammatory conditions. An analysis of the pathophysiology and healing of musculoskeletal injuries questions the use of NSAIDs in many treatment protocols. Because NSAIDs have profound side effects, they should not automatically be the first choice for treating musculoskeletal injuries.
Nonsteroidal anti-inflammatory drugs (NSAIDs) annually account for 70 million prescriptions and 30 billion over-the-counter (OTC) medications sold in the United States alone. Some formulas are safe enough to be sold OTC for use in infants with fever, while others are available only as a prescription medication and are a leading cause of iatrogenic reactions, hospitalizations, and death.
“This study is important because it showed that adverse drug events were found in 23% of ambulatory patients, a rate five times as high as that found in another recent study of the community-living elderly,” said Dr. Gandhi. “We probably found such a high rate because we called patients directly, while other studies have relied mainly on chart review.”
No one had ever analyzed and combined ALL of the published literature dealing with injuries and deaths caused by government-protected medicine. That has now changed. A group of researchers meticulously reviewed the statistical evidence and their findings are absolutely shocking. This fully referenced report shows the number of people having in-hospital, adverse reactions to prescribed drugs to be 2.2 million per year. The number of unnecessary antibiotics prescribed annually for viral infections is 20 million per year. The number of unnecessary medical and surgical procedures performed annually is 7.5 million per year. The number of people exposed to unnecessary hospitalization annually is 8.9 million per year. The most stunning statistic, however, is that the total number of deaths caused by conventional medicine is an astounding 783,936 per year!!!
Prescribed drugs are now a major cause of morbidity and mortality, particularly in the elderly. The extent of this pandemic is described and its likely causes in primary care are identified: unnecessary prescribing, imprecise diagnosis, inadequate undergraduate and postgraduate education in pharmacology and therapeutics, the uncritical application of evidence-based medicine, the outstanding development of new drugs and their sometimes unjustified promotion. Urgent action is recommended under seven headings, by health administration, epidemiologists, medical educators and prescribing doctors.
Diagnostic error is commonly multifactorial in origin, typically involving both system-related and cognitive factors. The results identify the dominant problems that should be targeted for additional research and early reduction; they also further the development of a comprehensive taxonomy for classifying diagnostic errors.
Development, Testing, and Findings of a Pediatric-Focused Trigger Tool to Identify Medication-Related Harm in US Children’s Hospitals
Adverse drug event rates in hospitalized children are substantially higher than previously described. Most adverse drug events resulted in temporary harm, and 22% were classified as preventable. Only 3.7% were identified by using traditional voluntary reporting methods. Our pediatric-focused trigger tool is effective at identifying adverse drug events in inpatient pediatric populations.
Among Medicare recipients, between 2002 and 2007, the frequency of complex fusion procedures for spinal stenosis increased while the frequency of decompression surgery and simple fusions decreased. In 2007, compared with decompression, simple fusion and complex fusion were associated with increased risk of major complications, 30-day mortality, and resource use.
No-fault Compensation for Treatment Injury in New Zealand: Identifying Threats to Patient Safety in Primary Care
New Zealand’s no-fault treatment injury claims database provides information about primary care patient safety events from an unusual ‘no-fault’ perspective. This analysis reinforces previous research identifying medication as a high-risk primary care activity and further identifies other primary care activities (dental care, injections, venepuncture, cryotherapy and ear syringing) as carrying important risks for patient harm.
“Non-steroidal anti-inflammation drugs (NSAIDs) are one of the most common causes of reported serious adverse reactions to drugs, with those involving the upper gastrointestinal tract (GIT), the cardiovascular system and the kidneys being the most common. Much of the focus on NSAID adverse effects has been on GIT consequences, with good reason. A U.S. study found the rate of deaths from NSAID-related GIT adverse effects is higher than that found from cervical cancer, asthma or malignant melanoma.”
While it is true that epidural steroid injections (ESI) are not FDA approved, Medicare, Medicaid, workers’ compensation and most other insurers continue to pay hundreds of millions of dollars per year for this controversial procedure. Ironically, on every vial of Kenalog (a popular steroid used for epidural injections) there is actually a warning against its use for epidural injections, yet proceduralists continue to use it.