During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades.
To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence.
Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered.
Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors.
The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.
Comment In: Arch Intern Med. 2001 Jun 11;161(11):146011386902
BACKGROUND: Drug therapy for Crohn's disease and ulcerative colitis is based on anti-inflammatory and immunodulating drugs, nutritional support and surgical resection. Recently, new drugs have been introduced. AIM: To report drug prescriptions, costs and adverse reactions among inflammatory bowel disease patients in Sweden between 1988 and 1997. METHODS: Drug use was calculated from the national Diagnosis and therapy survey and drug costs from prescriptions and drug sales. Adverse drug reactions were obtained from the Medical Products Agency's National Pharmacovigilance system. RESULTS: The annual drug exposure for Crohn's disease was 0.55 million daily doses per million population, mainly supplementation and aminosalicylic acids. Mesalazine and olsalazine had 61% within this group. For ulcerative colitis patients, drug exposure was 0.61 million daily doses per million per year and aminosalicylic acids fell from 70% to 65%. For inflammatory bowel disease patients, corticosteroids and nutritional supplementation were common. The annual average cost for inflammatory bowel disease drugs was 7.0 million US dollars. Annually, 32 adverse drug reactions were reported, mainly haematological reactions such as agranulocytosis and pancytopenia (60%), followed by skin reactions. Only two deaths were reported. Aminosalicylic acids were the most commonly reported compounds. CONCLUSIONS: Drug use for inflammatory bowel disease in the pre-biologic agent era rested on aminosalicylic acid drugs and corticosteroids with stable levels, proportions and costs. The level of adverse drug reactions was low but haematological reactions support the monitoring of inflammatory bowel disease patients.
Severe facial and scalp dermatitis following the use of permanent hair dyes has been reported in several cases. Para-phenylenediamine (PPD) is known as a potent contact allergen, and PPD is allowed in hair dye at a concentration of 6%. Hair dye reactions are usually diagnosed by the patients themselves, and adverse reactions to hair dye may not necessarily be recorded by the health care system, unless the reactions are especially severe. Based on this assumption, we suspected that hair dye dermatitis was occurring more frequently than reported in the literature. Consumer complaint-based data were obtained by advertising for persons with adverse reactions to hair dye. Among those responding to the advertisement, 55 cases of severe, acute allergic contact dermatitis were identified. The main symptoms were severe oedema of the face, scalp and ears, and clinically this was often mistaken for angio-oedema. The 55 cases comprised a total of 75 visits to the health service and 5 admissions to hospital. 18 persons had sick leave, which supports the impression of very severe dermatitis reactions. 60% were treated with antihistamine, while 52% were treated with corticosteroids. 29% of the cases were patch tested and all were found positive to PPD. Our data presented here clearly show that PPD and its derivatives in hair dye at the present concentrations presents a significant health risk for the population. Furthermore, the severe acute allergic skin reactions are often misdiagnosed in the health care system. The frequency of allergic contact dermatitis resulting from hair dye is likely to be underestimated. New methods to survey the frequency of adverse reactions should be considered.
In September 1999, several Canadian provinces had place-of-sale restrictions lifted that had limited the sale of acetaminophen >325 mg and packages >24 tablets (any strength) to pharmacies only. This allowed the sale of all strengths of immediate-release acetaminophen in all package sizes in nonpharmacy locations. This study's purpose was to explore the effect that lifting restrictions on acetaminophen place of sale may have had on reported hospitalizations in Canada related to acetaminophen overdose toxicity. Using hospital discharge data, provinces with no preexisting restrictions on place of sale were compared with those in which restrictions were lifted in September 1999. Cases of reported APAP overdose included ICD-9/9-CM code 965.4, ICD-9 code E850.2, or ICD-9-CM code E850.4. Cases with reported acute liver toxicity included ICD-9/9-CM codes 570, 572.2, 572.4, V42.7, or procedure code 50.5. There were no significant differences between the 1.5-year periods pre- and post-September 1999 in annual incidence rates per 100,000 persons ages >/=12 years of hospitalizations reported with acetaminophen overdose, either overall or limited to those with death as an outcome, or in hospitalization reports with both acetaminophen overdose and acute liver toxicity, either overall (provinces with no restrictions: pre = 0.70, post = 0.80, P = 0.6328; provinces with restrictions lifted in September 1999: pre = 0.49, post = 0.47, P = 0.8649) or limited to those with death as an outcome (provinces with no restrictions: pre = 0.22, post = 0.12, P = 0.3030; provinces with restrictions lifted in September 1999: pre = 0.13, post = 0.09, P = 0.3589). In conclusion, the decision to lift Canadian place-of-sale restrictions increased acetaminophen availability and did not increase the rate of reported hospitalizations related to acetaminophen overdose toxicity.
Linked administrative health care utilization databases offer potential benefits for postmarketing surveillance. The value of the Saskatchewan datafiles in an acute adverse event signalling scheme has been evaluated using two benzodiazepines. The first 20,000 patients dispensed lorazepam and the first 8525 patients dispensed alprazolam were followed through the datafiles over the year after their initial prescription of the relevant drug, and all medical services occurring during treatment were recorded. The most frequent adverse drug reactions to benzodiazepines are drowsiness, depression, impaired intellectual function and memory, lethargy, impaired coordination, dizziness, nausea and/or vomiting, skin rash, and respiratory disturbance. Data from our study showed that sleep disorders, depressive disorders, dizziness and/or vertigo, respiratory symptoms, esophagus and stomach disorders, and inflammatory skin conditions occurred significantly more often in the first 30 days after the initial prescription than in the succeeding six months in both drug groups, indicating that they are important adverse events. There are several limitations to the methodology; however, the results of the analysis indicate that the use of administrative health care utilization datafiles in a systematic assessment to signal potential acute adverse drug reactions is a feasible proposition, but further studies are required to assess whether events are real adverse reactions.
The aim of the study was to explore the profile of acute and long-term psychiatric side effects associated with mefloquine.
Subjects (n = 73) reported to a Danish national register during five consecutive years for mefloquine associated side effects were included. Acute psychiatric side effects were retrospectively assessed using the SCL-90-R and questions based on Present State Examination (PSE). Subjects reporting suspected psychotic states were contacted for a personal PSE interview. Electronic records of psychiatric hospitalizations and diagnoses were cross-checked. Long-term effects were evaluated with SF-36. SCL-90-R and SF-36 data were compared to age- and gender matched controls.
In the SCL-90-R, clinically significant scores for anxiety, phobic anxiety and depression were found in 55%, 51%, and 44% of the mefloquine group. Substantial acute phase psychotic symptoms were found in 15% and were time-limited. Illusions/hallucinations were more frequently observed among women. Cases of hypomania/mania in the acute phase were 5.5%. Significant long-term mental health effects were demonstrated for the SF-36 subscales mental health (MH), role emotional (RE), and vitality (VT) in the mefloquine group compared to matched controls.
The most frequent acute psychiatric problems were anxiety, depression, and psychotic symptoms. Data indicated that subjects experiencing acute mefloquine adverse side effects may develop long-term mental health problems with a decreased sense of global quality of life with lack of energy, nervousness, and depression.
Ever since the advent of pediatric vaccination, individuals have expressed concerns about both its risks and benefits. These concerns have once again resurfaced among some segments of the population and could potentially undermine national vaccination programs. The views of the public, however, must be considered and respected in the formulation of vaccination policy. We have conducted an analysis of the pediatric vaccination "debate" in the Canadian context. We believe that there is common ground between those who support pediatric vaccination and those who are concerned about these programs. Based on our findings, we believe that the goal of public health authorities should be to maintain trust in vaccines by continuing to meet certain reciprocal responsibilities. To do so, we recommend the following: 1) increased investment in adverse event reporting systems; 2) request for proposals for consideration of a no-fault compensation program; 3) developing pre-emptive strategies to deal with potential vaccine risks; 4) further examination of mechanisms to improve communication between physicians and parents concerned about vaccination. All of these approaches would require additional investment in pediatric vaccination. However, such an investment is easy to justify given the benefits offered by pediatric vaccination and the ramifications of failing to maintain confidence in vaccination programs or missing a vaccine-related adverse event.
Comment In: Can J Public Health. 2006 Mar-Apr;97(2):86-916619991
The trend towards polypharmacy is increasing among the elderly, and associated with this trend is an increased risk of adverse drug effects and drug-drug interactions. Our objective was to assess whether drug adverse effects reported by patients are in general agreement with those identified by a physician.
We evaluated the medication of 404 randomly selected individuals aged 75 years or older by means of interviews carried out by trained nurses and examinations conducted by a physician. The medication used by these patients was recorded prior to the physician's examination and modified thereafter if considered appropriate. Adverse effects noted by the physician were compared to those self-reported by the patients.
Almost all of the patients (98.8%) were using at least one drug, and the mean total number of drugs used was 6.5. Adverse effects were self-reported by 11.4% of the patients, whereas the physician observed apparent adverse drug effects in 24.0% of the patients. No adverse effects were reported in 53.2% of the patients. There were only seven patients that had adverse effects that were both self-reported and identified by the physician, and only four of these patients reported the same adverse effect that had been identified by the physician.
There was a great disparity between the adverse effects identified by the physician and those reported by the patients themselves. Based on our results, it would appear that elderly people tend to neglect adverse drug effects and may consider them to be an unavoidable part of normal ageing. Therefore, physicians should enquire about possible adverse effects even though elderly patients may not complain of any drug-related problems.
The frequency and characteristics of adverse drug events (ADEs) in children hospitalized in the paediatric department of Ullevaal University Hospital, Norway, were determined using intensive monitoring. Of 579 children treated with drugs, 28% experienced ADEs; 7% at the time of admission, 18% during hospitalization and 9% after discharge. All children treated for cancer, 19% treated with anti-infective drugs, 15% treated with antiasthmatics and 10% treated with drugs affecting the nervous system experienced ADEs. The most frequent events were gastrointestinal, CNS- and skin reactions and 19% were considered as serious. ADEs caused 6% of the admissions and 44% required interventions. Most ADEs were found by screening patient records, where physicians mostly described adverse drug events requiring interventions and nurses described less serious events. Parents reported 14% of the events, of which a majority were CNS reactions. CNS reactions may be more common than expected and observations by parents are important when investigating such reactions in children. Conclusions: ADEs, mainly gastrointestinal, CNS and skin reactions related to drugs affecting the nervous system, anti-infectives and antiasthmatics, were seen in 28% of the patients. The reporting of events by parents was a useful supplement to the screening of patient records.