Trends in prescription of strong opioids for 41-80 year old Norwegians, 2005-2010.

BACKGROUND: The use of strong opioids is affected by various influences such as increasing emphasis on adequate pain control and increasing measures to counteract opioid abuse. This study will examine trends of analgesic strong opioid use in an older population. METHODS: The study population includes people aged 41-80 who filled at least one prescription for analgesic strong opioids in 2005-2010. Information was obtained from the Norwegian Prescription Database (NorPD), that is, all prescriptions filled in Norwegian pharmacies. RESULTS: Annual rates per 1000 population of opioid users increased from 8.6/1000 in 2005 to 13.3/1000 in 2010 with the greatest increases for the oldest. Oxycodone showed the highest use in Norway and the greatest increase. Buprenorphine showed little use in 2005 but ranked second highest in 2010 at 3.3/1000. Morphine use remained stable over the years. Mean annual amount in defined daily doses (DDDs)/person decreased in the youngest age groups over 2005-2010 and showed a pattern of decreasing amounts with increasing age. About 20% of the study population received opioids from more than two prescribers and annually 20% received more than one type of opioid. High end users were younger and used more prescribers. CONCLUSIONS: Rate of analgesic strong opioid use, particularly oxycodone and buprenorphine, in this older age group increased annually. The pattern of increasing opioid use is consistent with an increased focus on pain control but may also be influenced by altered reimbursement policies and the new convenient pharmaceutical formulations.

Trends in diabetes treatment in Canadians, 1994-2004.

OBJECTIVE: To examine trends in the treatment of diabetes using the biannual interviews of the longitudinal National Population Health Survey (NPHS), 1994-2004 as they relate to changes in Clinical Practice Guidelines (CPGs). METHODS: A sample of 17 276 Canadians 18 years and older was selected for repeated interviews at two-year intervals from 1994 to 2004 for the NPHS. The population used for this study includes all respondents aged 40 to 79 for any of the cycles. RESULTS: CPGs issued by the Canadian Diabetes Association in 1998 and 2004 recommend a stepwise introduction of lifestyle changes, to be followed by single then multiple oral antidiabetic agents (OA), and finally insulin until adequate control is achieved. While the use of OA increased, only a small proportion indicated diet or physical exercise as part of their treatment; those with no drug treatment reported less diet modification and physical exercise. Antihypertensives and statin use in Canadians with diabetes increased to double that of Canadians overall, but remained underutilized. CONCLUSION: This study provides an update on the treatment of diabetes in Canada between 1994 and 2004. While some changes in diabetes treatment were compatible with CPGs, there is room for improvement, especially in lifestyle modifications.

Oral contraceptive use.

OBJECTIVES: This article profiles Canadian women aged 15 to 49 who use oral contraceptives (OCs), and compares certain of their characteristics with those of non-users. It also examines associations between OC use and selected characteristics, including cardiovascular risk factors. DATA SOURCE: The data are from the cross-sectional household component of Statistics Canada's 1996/97 National Population Health Survey. The analysis is based on a sample of 21,996 women aged 15 to 49, weighted to represent an estimated 7.6 million women. ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate the percentage of women aged 15 to 49 who use OCs and to compare selected health behaviours of users and non-users. A multiple logistic regression model was used to model relationships between selected characteristics and OC use. MAIN RESULTS: An estimated 1.3 million women aged 15 to 49, or 18%, reported using OCs in 1996/97. OC use was significantly associated with being young, unmarried, sexually active, and having prescription drug insurance and relatively high education. About one-third of OC users also smoked.

The effect of alcohol abuse on the risk of NSAID-related gastrointestinal events.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of gastrointestinal (GI) complications. Excessive alcohol consumption may further increase this risk and the FDA is requiring warnings on over-the-counter (OTC) NSAIDs. Our objective is to evaluate the risk of NSAID-related GI events for persons with a history of alcohol abuse. METHODS: This case control study used data from Saskatchewan Health. Cases consisted of 1083 patients hospitalized for severe GI events, whereas the control group consisted of 14,754 persons without such hospitalizations. RESULTS: Five percent of cases and 1.9% of controls had a history of treatment for alcohol abuse. The presence of either NSAID use or a history of alcohol abuse led to an odds ratio (OR) of 2.9* for severe GI events, whereas the presence of both risk factors simultaneously led to an OR of 10.2* (additive would be 5.8). Similarly, the presence of ibuprofen and naproxen use, which are OTC in the USA, without alcohol abuse led to an OR of 1.9*, whereas alcohol abuse by itself led to an OR of 2.4*. The presence of both OTC NSAIDs and alcohol abuse simultaneously, led to an OR of 6.5 (additive would be 4.3). Thus with both risk factors present, the resulting risk ratio is greater than the additive risk of the separate risk factors. CONCLUSIONS: The Food and Drug Administration (FDA) warning concerns concurrent use of alcohol with NSAIDs, whereas the present study presents the effect of long term alcohol abuse. Further research is needed to separate these two issues to allow physicians to provide the best advice to their patients. *Statistically significant at p<0.05.

Corticosteroid-induced adverse psychiatric effects: incidence, diagnosis and management.

Reports of corticosteroid-induced adverse psychiatric effects began to appear in the literature soon after the introduction of these medications in the 1950s. Unfortunately, early studies relied on informal classification and measurement procedures and tended to utilise nonspecific descriptive terminology (such as steroid psychosis'). A growing number of contemporary investigations have begun to address these problems. However, the literature remains surprisingly undeveloped from a pharmacoepidemiological perspective, consisting largely of case reports and case series. The objective of this review is to summarise published data concerning corticosteroid-induced adverse psychiatric effects. A clinical perspective will be adopted since opportunities to minimise the impact of corticosteroid-induced adverse effects tend to present themselves most readily within the sphere of clinical management. Some of the psychiatric adverse effects of corticosteroids are mild, and not necessarily clinically significant. However, several serious psychiatric syndromes can be caused by corticosteroids: substance-induced mood disorders (with depressive, manic and mixed features), substance-induced psychotic disorders and delirium. While certain clinical groups may be at greater risk of corticosteroid-induced adverse psychiatric effects, corticosteroid-induced psychiatric toxicity is remarkably unpredictable. The literature regarding prevention and treatment of corticosteroid-induced adverse psychiatric effects is poorly developed. As a result, the emphasis of this review is on clinical and epidemiological evidence linking specific adverse effects to corticosteroid medications. However, clinical reports do provide some practical guidance for prevention and treatment, and these are summarised as well. A variety of pharmacological strategies for treatment and prevention have been proposed. Education and support also appear to be important, and perhaps neglected.

Comparing two different approaches to measuring drug use within the same survey.

Respondents to the National Population Health Survey in Canada (1996 97) were asked two types of questions about drug use that allowed a comparison of the responses. The first question was about self-reported drug use categories: "In the past month, did you take [e.g., antidepressants]?" The second asked about specific drugs: "What specific medications did you take over the last two days?" Responses to the latter were coded according to the main chemical entity and then grouped in specific drug product categories similar to the first question's self- reported categories. The two sets of drug use categories were cross-tabulated for the 62,588 respondents who were 20 years of age and older. The proportion of persons who reported taking specific drugs who had not previously answered "yes" to the question related to the corresponding self-reported drug use category ranged from a low of 4.8% for insulin/oral hypoglycemics to a high of 43.7% for narcotic analgesics. Various reasons for these discrepancies are discussed. A series of logistic regression models relating the discrepancies to respondent characteristics shows that there is no clear pattern of variables associated with the discrepancies. These results show that surveys should be carefully planned to reflect the type of information needed.

Differences between males and females in risk of NSAID-related severe gastrointestinal events.

PURPOSE: NSAID use has long been established as a risk factor for severe gastrointestinal (GI) events. It is also known that age and gender affect the risk of such events independently of nonsteroidal antiinflammatory drug (NSAID) use. The objective of the present study is to distinguish between gender as an independent risk factor for severe GI events, and the differences between males and females in risk of NSAID-related severe GI events. METHODS: The study design was a nested case-control study. During the study period, 1029 cases were hospitalized with GI bleeds and/or perforations and 14 481 controls without such GI events were selected. Exposure consisted of the number of NSAID prescriptions dispensed by a pharmacy, prior to the data of hospitalization for cases and a corresponding date for controls. RESULTS: Males have a risk of serious GI events 1.4 times greater than females, independent of NSAID use. However, females have the greater increase in risk of NSAID-related GI events, e.g. at four prescriptions women have an odds ratio (OR) of 7.4 (p<0.05), while men have a corresponding OR of 3.2 (p<0.05). The increasing risk of severe GI events with number of NSAID prescriptions was considerably greater for females than for males, indicating effect-modification. In a stratified analysis by age and gender, it was clear that gender was the greater influence. Various metabolic and epidemiological potential explanations are discussed. CONCLUSIONS: Age and gender are separate risk factors for GI complications as related to NSAID use. Although implied in other studies, the effect of gender on the risk of NSAID-related GI events is clearly stated in this study.

Risk of suicide attempts after benzodiazepine and/or antidepressant use.

PURPOSE: Recent publications imply the existence of associations between psychotropic drugs use and risk of suicide. Some studies have measured the tissue level of these drugs in suicide deaths, while others compared toxicity indices, defined as number of suicide deaths per million prescriptions for individual antidepressants. Few of these studies used unexposed controls. The objective of this cohort study was to evaluate suicide attempts in subjects recently exposed to benzodiazepines and/or antidepressants, as compared to unexposed controls. METHODS: A population of 225,796 persons with prescriptions for benzodiazepines were selected from the Saskatchewan Health Data Bases. Controls consisted of 97,862 individuals who did not receive benzodiazepines. RESULTS: Stratifying the populations into antidepressant users and non-antidepressant users indicated that nonantidepressant users had statistically significant associations between suicide attempts and benzodiazepine use (odds ratio (OR) = 6.2), antipsychotic use, (OR = 2.6), and a history of past treatment for drug/alcohol abuse (OR = 13.4). Antidepressant users showed a statistically significant relation only with past treatment for drug/alcohol use (OR = 5.8). It is argued that the large OR for antidepressant use is due to confounding by indication. If so, the concept of toxicity index is misleading and should not be used. CONCLUSIONS: The association between benzodiazepine use and attempted suicide is especially high for nonantidepressant users, for the young, and for males. Whether this relationship is causal or not, physicians should be aware of the high potential for suicide attempts when prescribing benzodiazepines for patients in these high risk groups.

The potential for Simpson's paradox in drug utilization studies.

PURPOSE: Simpson's paradox is a type of severe confounding wherein a confounding variable changes the direction of an association. METHODS: This article demonstrates Simpson's paradox with three cohorts of naproxen users (new users, chronic users, and combined users) who were compared on the age/sex distribution of further naproxen use. Hypothetical new and chronic user populations were constructed with the same proportions for further naproxen use as their original counterparts. RESULTS: The hypothetical combined population showed an age/sex distribution opposite to that of the original combined population. CONCLUSIONS: This example of Simpson's paradox is a significant finding as many drug utilization studies do not distinguish between component populations.

A prospective study of falls after benzodiazepine use: a comparison of new and repeat use.

Although research has consistently demonstrated an increased risk for falls and fall-related fractures among persons receiving benzodiazepine (BZD) medications, the association between new as compared with chronic use and fall-related morbidity among different age groups is less clear. The objectives of this prospective cohort study were to examine the associations between BZD sedative and tranquillizer use and fall-related hospitalizations within 28 days of the fill date, and to explore variations in risks among new (after the first prescription) and chronic (after the third prescription) BZD users of different ages. Data were derived from the Saskatchewan Health linked databases for the years 1979-1986. Fall rates increased with age (especially beyond 70 years) and were highest among those receiving BZD sedatives and tranquillizers compared with controls for both new and chronic users. After adjusting for age, sex and selected health and social factors, a significantly increased risk of fall-related hospitalization was found among new BZD sedative (OR=2.8) and tranquillizer (OR=2.0) users compared with controls, and this risk was only slightly reduced among chronic BZD sedative (OR=2.4) and tranquillizer (OR=1.6) users. These risk estimates were consistent across age, with the exception that chronic BZD tranquillizer use remained significant only among those aged 70 years and older.

New evidence on benzodiazepine use and falls: the time factor.

The objectives of this prospective study were to calculate incidence rates for fall-related hospitalization, to compare the effect of risk factors among benzodiazepine (BZD) users and unexposed controls, and to examine variations in risks according to length of time following a BZD prescription. Data were derived from Saskatchewan Health linked data bases, leading to information on 468 hospitalizations for injury due to falls among a study population of 321422. Incidence rates per 10000 within 28 days of the prescription fill date were 26.2, 12.1 and 9.0 for BZD sedative users, BZD tranquillizer users and for unexposed controls, respectively. Incidence rates increased with age, and were higher for women than for men. Results from multivariate logistic regression models also showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women. A history of treatment for alcohol abuse was a very strong risk factor for falls among both men (odds ratio, 10.7) and women (odds ratio, 4.3). The highest risk of serious injury due to falls was within 15 days of filling the prescription, with an odds ratio of 3.6 for BZD sedatives and 2.6 for BZD tranquillizers. Risk decreased with further increase of time after the BZD fill date. For the individual BZD, flurazepam and triazolam showed the highest increase in risk with odds ratios of 3.4 and 2.7, respectively, while oxazepam, lorazepam and diazepam showed odds ratios of 2.2, 2.0 and 1.8 (all odds ratios mentioned are statistically significant at p < 0.05).

Risk of traffic accident injury after a prescription for a benzodiazepine.

The objective of this study was to assess the risk of hospitalization for injuries received in traffic accidents after a first prescription for benzodiazepines (BZD) was filled. Saskatchewan Health supplied study populations of 78,000 adults who received BZD hypnotics, 148,000 who received BZD anxiolytics, and 98,000 control subjects. These populations were monitored for 2 months after the index prescription fill-date for hospitalizations due to traffic accidents. Analysis showed an odds ratio (OR) of 3.9 (1.9 to 8.3) for persons taking BZD hypnotics and an OR of 2.5 (1.2 to 5.2) for those taking BZD anxiolytics, with regards to hospitalization due to traffic accidents within 4 weeks after the prescription was filled. Within 2 weeks after the prescription was filled, the Or had risen to 6.5 (1.9 to 22.4) for hypnotics and 5.6 (1.7 to 18.4) for anxiolytics. After 1 week, the ORs were even higher (9.1 and 13.5), but the confidence limits were wide. The highest risk groups were the youngest age group (20 to 39 years old) and males. From a public health view, the high ORs are of concern and action for prevention is needed.