Objective: To assess whether use of oral glucocorticoids is associated with cardiovascular and cerebrovascular morbidity. Design and setting: Nested case–control study within a cohort of patients (⩾ ...50 years old) with at least one prescription for oral or non-systemic glucocorticoids. Data were from the general practice research database. Patients: 50 656 patients were identified with a first record for ischaemic heart disease (International classification of diseases, ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke or transient ischaemic attack (ICD-9 codes 430–436), or heart failure (ICD-9 code 428) between 1988 and 1998. One control was matched to each case by sex, age, general practice, underlying disease, and calendar time. Main outcome measure: Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using oral glucocorticoids compared with non-users. Results: There was a significant association between ever use of oral glucocorticoids and any cardiovascular or cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to 1.29). The association was stronger for current use of oral glucocorticoids than for recent or past use. Among current users, the highest ORs were observed in the group with the highest average daily dose, although the dose–response relation was not continuous. Current use was associated with an increased risk of heart failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between patients with rheumatoid arthritis, patients with chronic obstructive pulmonary disease, and patients without either of the two conditions. Also, current use was associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95% CI 1.11 to 1.29). Conclusions: Oral glucocorticoid use was identified as a risk factor for heart failure. However, the evidence remains observational and only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes.
Purpose
Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe ...the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases.
Methods
Annual prevalence per 10,000 person-years (PYs) was calculated for 2001–2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors SSRIs or tricyclic antidepressants TCAs) and major indications.
Results
The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15–57 % and 39–69 % for depression respectively).
Conclusion
Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.
To study the association between use of antiepileptic drugs (AEDs) and risk of fractures.
The authors obtained data from the General Practice Research Database (GPRD). A case-control study was nested ...within a cohort of patients with active epilepsy. Cases were patients with a first fracture after cohort entry. Up to four controls were matched to each case by practice, sex, year of birth, timing of first epilepsy diagnosis, index date, and duration of GPRD history. Cumulative exposure to AEDs was assessed by summing the duration of all AED prescriptions. A distinction was made between AEDs that induce the hepatic cytochrome P-450 enzyme system and AEDs that do not. Medical conditions and drugs known to be associated with bone metabolism or falls were evaluated as potential confounders. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs.
The study population comprised 1,018 cases and 1,842 matched controls. The risk of fractures increased with cumulative duration of exposure (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71 to 6.34). Risk estimates were higher in women than in men. There was no difference between users of AEDs that induce and AEDs that do not induce the hepatic cytochrome P-450 system.
Long-term use of AEDs was associated with an increased risk of fractures, especially in women. More research on mechanisms of AED-induced bone breakdown and female vulnerability to the effects of AEDs on bone health is warranted.
Summary
Background
Microscopic colitis (MC) is a chronic bowel disorder characterised by watery diarrhoea. Nonsteroidal anti‐inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective ...serotonin reuptake inhibitors (SSRIs) and statins have been associated with MC. However, underlying mechanisms remain unclear.
Aim
To study the association between exposure to these drugs and MC, with attention to time of exposure, duration, dosage and combined exposure, and to test hypotheses on underlying pharmacological mechanisms.
Methods
A case–control study was conducted using the British Clinical Practice Research Datalink. MC cases (1992–2013) were matched to MC‐naive controls on age, sex and GP practice. Drug exposure was stratified according to time of exposure, duration of exposure or dosage. Conditional logistic regression analysis was applied to calculate adjusted odds ratios (AORs).
Results
In total, 1211 cases with MC were matched to 6041 controls. Mean age was 63.4 years, with 73.2% being female. Current use of NSAIDs (AOR 1.86, 95% CI 1.39–2.49), PPIs (AOR 3.37, 95% CI 2.77–4.09) or SSRIs (AOR 2.03, 95% CI 1.58–2.61) was associated with MC compared to never or past use. Continuous use for 4–12 months further increased the risk of MC. Strongest associations (fivefold increased risk) were observed for concomitant use of PPIs and NSAIDs. Statins were not associated with MC.
Conclusions
Current exposure to NSAIDs, PPIs or SSRIs and prolonged use for 4–12 months increased the risk of MC. Concomitant use of NSAIDs and PPIs showed the highest risk of MC. Acid suppression related dysbiosis may contribute to the PPI effect, which may be exacerbated by NSAID‐related side‐effects.
•Depression was the most common indication in both databases.•About one half of the diagnoses were non-selected indications (other than depression, anxiety, sleep disorders, migraine/headache, ...neuropathic pain, fibromyalgia and other mental and behavioral disorders) in both databases.•Non-selected indications showed an increase in The Netherland and decreased in Catalonia in 2010–2015.•Tricyclic antidepressants were the most commonly prescribed antidepressant in NIVEL-PCD, and selective serotonin reuptake inhibitors in SIDIAP.
Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings.
A longitudinal study of new antidepressant users aged ≥65 was conducted, with data from the Nivel-PCD (The Netherlands) and SIDIAP (Catalonia) databases (2010–2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described.
A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65–69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased.
It is not mandatory for physicians to register a diagnosis with each prescription.
Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.
To investigate the risk of various types of infections (pneumonia and urinary tract infection (UTI)), and infection-related mortality in patients with gout compared with population-based controls. A ...retrospective cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD). All patients with a first diagnosis of gout and aged >40 years between January 1987-July 2014, were included and matched with up to two controls. Time-varying Cox proportional hazards models were used to estimate the risk of infections and mortality. 131,565 patients and 252,763 controls (mean age: 64 years, 74% males, mean follow-up of 6.7 years) were included in the full cohort. After full statistical adjustment, the risk of pneumonia was increased (adj. HR 1.27, 95% CI 1.18 to 1.36), while the risk of UTI (adj. HR 0.99, 95% CI 0.97 to 1.01) was similar in patients compared to controls. No differences between patients and controls were observed for infection-related mortality due to pneumonia (adj. HR 1.03, 95% CI 0.93 to 1.14) or UTI (adj. HR 1.16, 95% CI 0.98 to 1.37). In conclusion, patients with gout did not have decreased risks of pneumonia, UTI or infection-related mortality compared to population-based controls.
Context: Few data exist on sex- and age-specific incidence and prevalence of idiopathic hyperprolactinemia and prolactinomas.
Objectives: Our objective was to assess incidence and prevalence of ...dopamine agonist-treated hyperprolactinemia by age and sex.
Design: From the PHARMO network, we identified an open cohort of patients who were ever dispensed dopamine agonists for hyperprolactinemia. The network includes complete medication histories for more than 2 million community-dwelling residents. Prolonged use of low-dose dopamine agonist is a reliable marker for hyperprolactinemia, provided that use for Parkinson’s disease and lactation withdrawal is excluded. Diagnoses were verified by prolactin values in a random subsample using the same network.
Results: We identified 11,314 subjects with at least one dispensing of dopamine agonist in the period 1996–2006, of whom 1607 subjects were considered to have dopamine agonist-treated hyperprolactinemia based on the prescribing pattern. The majority of patients were women (n = 1342, 84%). The diagnosis proved to be incorrect in only 1.5% of a random subsample. The estimated incidence rate of dopamine agonist-treated hyperprolactinemia for women was 8.7/100,000 person-years and for men 1.4/100,000 person-years. The highest incidence rate was found in women 25–34 yr of age: 23.9/100,000 person-years. The mean prevalence of ever treated female patients was almost five times higher (93.9/100,000) compared with male patients (19.6/100,000).
Conclusion: The incidence rates and the prevalence of dopamine agonist-treated hyperprolactinemia showed an overall preponderance in women, with a strong peak for women aged 25–34 yr. In men, no peak was found.
Incidence and prevalence of dopamine agonist-treated hyperprolactinemia shows an overall preponderance in women, with a strong peak for women aged 25–34 years.
Summary
Chronic kidney disease (CKD) is a risk factor for fractures. However, in hip fracture patients, CKD G3-G5 was associated with a higher mortality risk and not associated with a higher risk of ...subsequent non-hip fractures compared to eGFR > 60 ml/min. The higher mortality risk may, as competing risk, explain our findings.
Introduction
Chronic kidney disease (CKD) is a known risk factor for fragility fractures. Patients aged 50+ with a recent fragility fracture have an increased risk of subsequent fractures. Our aim was to evaluate the association between CKD stages G3–G5 versus estimated glomerular filtration rate (eGFR) > 60 ml/min and the risk of a new non-hip fracture or fragility fracture in patients with a first hip fracture.
Methods
Population-based cohort study using the UK general practices in the Clinical Practice Research Datalink. Associations between CKD stage and first subsequent fracture were determined using Cox proportional hazard analyses to estimate hazard ratios (HRs). To explore the potential competing risk of mortality, cause-specific (cs) HRs for mortality were estimated.
Results
CKD G3–G5 was associated with a lower risk of any subsequent non-hip fracture (HR: 0.90, 95%CI: 0.83–0.97), but not with the risk of subsequent major non-hip fragility fracture. CKD G3-G5 was associated with a higher mortality risk (cs-HR: 1.05, 95%CI: 1.01–1.09). Mortality risk was 1.5- to 3-fold higher in patients with CKD G4 (cs-HR: 1.50, 95%CI: 1.38–1.62) and G5 (cs-HR: 2.93, 95%CI: 2.48–3.46) compared to eGFR > 60 ml/min.
Conclusions
The risk of a subsequent major non-hip fragility fractures following hip fracture was not increased in patients with CKD G3–G5 compared to eGFR > 60 ml/min. Mortality risk was higher in both hip fracture and non-hip fracture patients with CKD G4 and G5. The higher mortality risk may, as competing risk, explain our main finding of no increased or even decreased subsequent fracture risk after a hip fracture in patients with CKD G3–G5.
Aims
To investigate short‐ and long‐term effects of real‐time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti‐diabetic ...medication.
Methods
A randomized controlled trial with two intervention groups and one control group involving 161 participants with Type 2 diabetes with suboptimal adherence. For 6 months, participants in the SMS group (n = 56) were monitored and received SMS reminders if they missed their medication. Participants in the non‐SMS group (n = 48) were only monitored. The control group (n = 57) was not exposed to any intervention. Primary outcome measure was refill adherence to oral anti‐diabetic medication. Multi‐level regression analyses were performed to examine intervention effects on adherence between and within groups after 1 and 2 years of follow‐up.
Results
At baseline, mean refill adherence was comparable between the groups. After 1 year, adherence in the SMS group was significantly higher than in the control group (79.5% vs. 64.5%; P < 0.001) and showed a significant improvement from baseline (+16.3%; P < 0.001). Mean adherence in the non‐SMS group reached 73.1% (+7.3%; P < 0.05), but did not differ from the control group (P = 0.06). After 2 years, the improved adherence in the SMS group persisted and remained significantly higher than in the control group (80.4% vs. 68.4%; P < .01), contrary to the non‐SMS group whose adherence approached baseline level again (65.5%).
Conclusions
This study shows the long‐term effectiveness of real‐time medication monitoring combined with SMS reminders in improving refill adherence. This new reminder system can strengthen the self‐management of people with diabetes.
What's new?
The innovative real‐time medication monitoring system evaluated in this study is the first to provide the opportunity to intervene only when patients forget to take their medication.
This study showed that receiving short message service (SMS) reminders only when a dose is missed results in a higher refill adherence, and is the first to demonstrate long‐term effectiveness of electronic reminders on adherence.
The real‐time medication monitoring reminder system can especially provide support for people who have problems taking their medication because of forgetfulness.
This system can also strengthen a person's self‐management, as medication management is an important aspect of self‐management.
Beliefs play a crucial role in medication adherence. Interestingly, the relationship between beliefs and adherence varies when different adherence measures are used. How adherence, in turn, is ...related to asthma symptoms is still unclear. Our aim was to investigate the relationship between beliefs (ie, necessities and concerns) about inhaled corticosteroids (ICS) and subjectively as well as objectively measure adherence and the agreement between these measures. Further, the relationship between adherence and asthma symptoms was examined.
A total of 280 patients aged 18-80 years who filled at least two ICS prescriptions in the preceding year were recruited to complete a questionnaire. The questionnaire included the Beliefs about Medicines Questionnaire to assess necessity beliefs and concerns about ICS, four questions about ICS use to measure self-reported adherence, and the Asthma Control Questionnaire to assess asthma symptoms. Proportion of days covered was used to determine pharmacy refill adherence.
Data from 93 patients with asthma were analyzed. Necessities were positively related to self-reported adherence (P = 0.01). No other associations were found between beliefs and subjective or objective adherence. There was no correlation between self-reported and refill adherence. Participants were significantly (P < 0.001) less adherent according to self-report data (24.4%) than according to pharmacy data (57.8%). No relationship was found between adherence and asthma symptoms.
Higher necessities are associated with higher self-reported adherence, suggesting that it could be more important to focus on necessities than on concerns in an attempt to improve adherence. Self-reported and refill adherence measurements cannot be used interchangeably. No relationship between adherence and asthma symptoms was found.
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