The study aims to determine the prevalence of concomitant use of benzodiazepines and opioids among community-dwelling older people with or without Alzheimer's disease (AD). An additional aim was to describe the factors associated with prolonged concomitant use, and the most commonly used combinations of these drugs.
This study utilized data from the register-based Medication Use and Alzheimer's disease (MEDALZ) study, including all community-dwelling residents of Finland who received a clinically verified AD diagnosis between 2005 and 2011 (n = 70 718) and their matched comparison persons without AD. After exclusion of individuals who were hospitalized throughout the follow-up, 69 353 persons with and 69 353 without AD were included in this study.
Benzodiazepines and related drugs (BZDRs) were used by 28 475 (41.1%) of those with and 24 506 (35.3%) of those without AD. Prolonged (greater than or equal to 90 days) concomitant use of BZDRs and opioids was more common among BZDR users without AD (N = 3936; 16.1%) than among those with AD (N = 2963; 10.4%). A shorter duration of concomitant use (1-89 days) revealed similar results, N = 3821; 15.6% and N = 3008; 10.6%, respectively. Prolonged concomitant use of BZDRs and opioids was associated with female sex, low socioeconomic position, most of the common comorbidities and history of substance abuse or long-term benzodiazepine use. The most commonly used combinations were Z-drug (31.7%) or benzodiazepine (29.9%) with a weak opioid.
Despite the recommendations and risks, the prevalence of concomitant BZDR and opioid use was common in older persons with or without AD. It is important to develop strategies to reduce unnecessary concomitant use of these drugs.
increasing number of persons reach very high age but few studies have investigated their drug use patterns.
to compare drug use among persons with Alzheimer's disease (AD) aged =90 years to persons without AD with similar age and to younger persons with AD.
register-based data were from the MEDALZ cohort including all community-dwelling persons diagnosed with AD 2005-11 in Finland. They were identified from Special Reimbursement register. One comparison person without AD was matched with age-, gender- and region of residence. Persons with AD were divided to those aged =90 years (N = 3,319) and
To study how long antidepressants initiated after diagnoses of Alzheimer's disease (AD) were used and factors associated with discontinuation of use among persons with Alzheimer's disease (AD). In addition, differences in duration of use between the antidepressants groups were compared.
Register-based Medication use and Alzheimer's disease (MEDALZ) cohort included 70,718 community-dwelling people with AD who were diagnosed during the years 2005-2011. For this study, the new antidepressant users were included after 1-year washout period (N?=?16,501; 68.6% females, mean age 80.9). The duration of antidepressant use was modeled with the PRE2DUP method. Factors associated with treatment discontinuation were assessed with Cox proportional hazard models and included age, gender, comorbid conditions and concomitant medications.
Median duration of the new antidepressant use period was 309 days (IQR 93-830). For selective serotonin reuptake inhibitor (SSRI) use, the median duration was 331 days (IQR 101-829), for mirtazapine 202 days (IQR 52-635), and for serotonin and norepinephrine reuptake inhibitors (SNRIs) 134 days (IQR 37-522). After 1-year follow-up, 40.8% had discontinued antidepressant use, 54.6% after 2 years and 64.1% after 3 years. Factors associated with treatment discontinuation were age over 85, male gender, diabetes, and use of memantine, opioids, and antiepileptics whereas benzodiazepines and related drugs and antipsychotic use were inversely associated with discontinuation.
Antidepressants are used for long-term among people with AD. Need and indication for antidepressant use should be assessed regularly as evidence on their efficacy for behavioral and psychological symptoms of dementia is limited.
Databases of prescription drug purchases are now widely used in pharmacoepidemiologic studies. Several methods have been used to generate drug use periods from drug purchases to investigate various aspects; e.g., to study associations between exposure and outcome. Typically, such methods have been fairly simplistic, with fixed assumptions of drug use pattern and or dose (for example, the assumed usage of 1 tablet per day). This paper describes a novel PRE2DUP method that constructs drug use periods from purchase histories, and verified by a validation based on an expert evaluation of the drug use periods generated by the method.
The PRE2DUP method is a novel approach based on mathematical modelling of personal drug purchasing behaviors. The method uses a decision procedure that includes each person's purchase history for each ATC code, processed in a chronological order. The method constructs exposure time periods and estimates the dose used during the period by considering the purchased amount in Defined Daily Doses (DDDs), which is recorded in the prescription register database. This method takes account of stockpiling of drugs, personal purchasing pattern; i.e., regularity of the purchases, and periods of hospital or nursing home care where drug use is not recorded in the prescription register. The method can be applied to a variety of drug classes with different doses and use patterns by controlling restriction parameters for each ATC class, or even each drug package. In the presented example, the PRE2DUP method was applied to a register-based MEDALZ-2005 study cohort. All drug purchases (3,793,085) recorded in the Finnish prescription register between 2002 and 2009 for persons with Alzheimer's disease (28,093) were included.
Results of the expert-opinion based validation indicate that PRE2DUP method creates drug use periods with a relatively high correctness. Drugs with varying patterns of use and drugs used on a short-term basis only require more precise parameters.
PRE2DUP method gives highly accurate drug use periods for most drug classes, especially those meant for long-term use.
The aim of our study was to investigate costs related to hospital care and drugs utilizing register-based data from five years before until two years after the diagnosis of Alzheimer's disease (AD) in a nationwide cohort.
Finnish nationwide MEDALZ cohort includes all incident cases with clinically verified diagnosis of AD diagnosed during 2005-2011. The study population included 70,718 persons with AD and age-, gender- and region-of-residence-matched control persons. Data of medical care costs was derived from the prescription register and hospital discharge register. Costs of hospital care were calculated according to Finnish healthcare system unit costs. Costs in six month periods before and after the diagnosis per person-years were analyzed.
Persons with AD had higher mean total medical care costs per person-years starting from 0.5-1 years before the diagnosis of AD and remained at a higher level until two years after the diagnosis. The difference in mean total medical care costs was at its highest at six months after the diagnosis (cost difference €5088). After that, persons with AD had costs that reached approximately double those without AD. Hospital care costs constituted the major share (78-84%) of the total medical care costs in both persons with and without AD, whereas drug costs had a minor role. Increase in drug costs was caused by anti-dementia drugs.
Costs of hospital stays constituted the most significant portion of medical care costs for persons with AD. Further research should be focused on the causes of hospitalization periods.
We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer's disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002-2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n?=?3121, 12.3%) than among persons with AD (n?=?2,920, 11.2%) (p?=?0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p?=?0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p?
The study aimed to investigate the incidence of antidepressant use in persons with and without Alzheimer's disease (AD) from 9?years before to 4?years after AD diagnosis and to examine the incidence of different antidepressant groups.
We used register-based data from the Medication use and Alzheimer's disease cohort including all Finnish persons diagnosed with AD in 2005-2011 with their age-matched and gender-matched comparison persons without AD. In this study, 62,104 persons with AD and 62,104 comparison persons were included. Data on dispensed antidepressants during 1995-2012 were collected from the Prescription Register. A 1-year washout period was utilized to measure the rate of new antidepressant users every 6-month period starting from 9?years before and until 4?years after the AD diagnoses. The incidence rate between persons with and without AD was compared with Poisson regression.
The incidence of antidepressant use in persons with AD was higher during the whole study period compared with that in persons without AD. The incidence rate was highest at 6?months after AD diagnosis (incidence rate ratio?=?5.22, 95% confidence interval 4.77-5.72). Selective serotonin reuptake inhibitors were the most frequently initiated group (61.3% of initiations in persons with AD).
In Central Finland, the age-specific incidence of hip fractures did not change between the years 1982-1983 and 1992-1993 though the total number of hip fractures increased by 11% due to population aging. The objective of this study was to define the current hip fracture rates and the characteristics of patients with hip fracture. The population at risk consisted of 240,000 persons living in the Central Finland Health Care District. Hip fracture patients were identified by using the hospital discharge register, the operation lists, and the register of the Department of Anesthesiology. Patients' residential status, weight, and height, date and time of hip fracture, place of accident and mechanism and type of fracture were obtained from medical records. A total of 597 patients, 415 (69.5%) women and 182 (30.5%) men, were admitted to the hospital for treatment of an acute hip fracture in 2002-2003. The mean age of the patients was 79 (SD 13) years. Among patients aged > or =50 years (n = 577), 80.8% of the hip fractures had occurred indoors, 97.6% with a low-energetic mechanism, and 22.7% during the nighttime. The ratio of trochanteric to cervical fractures was 2:3. Between 1992-1993 and 2002-2003, the total number of hip fractures increased by 70%, from 351 to 597. The fracture rates per 1000 person-years in the age group > or =55 years were 2.0 and 3.9 in 1992-1993 and 2.8 and 5.6 in 2002-2003 for men and women, respectively. The corresponding age-adjusted incidence rate ratio (IRR) for men was 1.36 (95% CI: 1.06 to 1.76), P = 0.017, and for women 1.25 (95% CI: 1.07 to 1.47), P = 0.006. Among men, the IRR was highest in the age group 75-84 years, IRR = 1.67 (95% CI: 1.08 to 2.65), while among women, it was highest in the age group > or =85 years, IRR = 1.33 (95% CI: 1.02 to 1.75). The total number of hip fractures almost doubled within 10 years, and the age-adjusted incidence rate increased in both sexes. The accretion of the hip fracture incidence was more than could be explained merely by changes in population size and structure.
Antipsychotics are recommended only for short-term treatment of severe behavioral and psychological symptoms of dementia. Our objective was to study the duration of antipsychotic use and factors associated with long-term use (365 days or over) among community-dwelling persons with Alzheimer?s disease (AD) during a 7-year follow-up. This was a nationwide register-based cohort study including all community-dwelling residents in Finland diagnosed with AD in 2005 (n=7217). The follow-up for antipsychotic use started 3 years before the diagnosis of AD and we applied a 7-year washout period to ascertain truly incident antipsychotic use. Follow-up ended on institutionalization, death or at the end of study period (December 31, 2009). Duration of antipsychotic use was modeled from individual purchase histories recorded in the Finnish Prescription Register. During the 7-year follow-up, 34% (2287/6740) of persons initiated antipsychotic use. Median duration of the first antipsychotic use period was 219 (interquartile range 85-583) days. Of those who discontinued antipsychotic use (n=1303), 44% restarted use later. Among users with at least one year of follow-up time after initiating antipsychotic use, prevalence of long-term use was 57% (893/1563). Long-term use was associated with initiation of use after AD diagnosis and choice of antipsychotic. Duration of use was more likely to be shorter among haloperidol users and longer among quetiapine users compared with risperidone users. In conclusion, long-term use of antipsychotics is frequent among community-dwelling persons with AD. Duration of use is not in line with the guidelines recommending time-limited use of antipsychotics.
The aim of this study was to investigate the prevalence of benzodiazepine and related drug (BZDR) use, especially long-term use, and associated factors among community-dwelling individuals with and without Alzheimer's disease (AD). We utilized data from the MEDALZ-2005 cohort, which includes all community-dwelling individuals diagnosed with AD in Finland at the end of 2005 and matched comparison individuals without AD. Register-based data included prescription drug purchases, comorbidities, and hospital discharge diagnoses. In this study, 24,966 individuals with AD and 24,985 individuals without AD were included. During the 4-year follow-up, we found that 45% (N = 11,312) of individuals with AD and 38% (N = 9534) of individuals without AD used BZDRs. The prevalence of long-term (= 180 days) BZDR use was more common among individuals with AD (30%) than individuals without AD (26%). The median durations of the first long-term use periods of BZDRs were 1.5 and 2 years for individuals with and without AD, respectively. Factors associated with long-term BZDR use included female sex, AD, schizophrenia, bipolar disorder, depression, coronary artery disease, and asthma/chronic obstructive pulmonary disease. The high prevalence of long-term BZDR use among individuals with AD is especially a cause for concern because long-term use may further impair cognition and may be associated with serious adverse events.