Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Residents of Long-Term Care Facilities.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Prescribing Appropriate Medicines to Older Adults: A Finnish Experience with the Web-Based Meds75+ Database.

The Finnish web-based Meds75+ database supports rational, safe and appropriate prescribing to older adults in primary care. This article describes the content and updating process of Meds75+ and demonstrates its applicability in everyday clinical practice. Meds75+ contains a classification (A-D) and recommendation texts for 450-500 drug substances when used in the treatment of older adults aged 75 years or older. The content of Meds75+ is continually updated. Each assessment of a drug substance begins with a structured collection of available information and research evidence. After that, an interdisciplinary expert panel discusses the classification and recommendation using a consensus method. A rolling 3-year updating cycle guarantees that all drug substances are reviewed regularly. Most drug substances are classified as class A (41%) (suitable, e.g. bisoprolol) or as class C (37%) (suitable with specific precautions, e.g. ibuprofen). One-fifth (20%) of the substances are in class D (avoid use, e.g. diazepam). Most commonly, older adults have purchased substances affecting the alimentary tract and metabolism (17%), the nervous system (16%) and the cardiovascular system (15%). In Finland, the proportion of older adults using class D substances (37%) has not changed between the years 2019 and 2022. Meds75+ has potential to support safer and more effective use of medications for older adults, since it offers up-to-date information on drug substances for healthcare professionals.

Predicting Alzheimer's disease from cognitive footprints in mid and late life: How much can register data and machine learning help?

BACKGROUND: Real-world data with decades-long medical records are increasingly available alongside the growing adoption of machine learning in healthcare research. We evaluated the performance of machine learning models in predicting the risk of Alzheimer's disease (AD) using data from the Finnish national registers. METHODS: We conducted a case-control study using data from the Finnish MEDALZ (Medication use and Alzheimer's disease) study. Altogether 56,741 individuals with incident AD diagnosis (age ≥ 65 years at diagnosis and born after 1922) and their 1:1 age-, sex-, and region of residence-matched controls were included. The association of risk factors, evaluated at different age periods (45-54, 55-64, 65+), and AD were assessed with logistic regression. Predictive accuracies of logistic regressions were compared with seven machine learning models (L1-regularized logistic regression, Naive bayes, Decision tree, Random Forest, Multilayer perceptron, XGBoost, and LightGBM). FINDINGS: 63.5 % of cases and controls were females and the mean age was 79.1 (SD = 5.1). The strongest associations with AD were observed for head injuries at age 55-64 (OR, 95 % CI 1.33, 1.19-1.48) and 65+ (1.31, 1.23-1.40), followed by antidepressant use (1.30, 1.22-1.38) at 55-64 and antipsychotic use (1.27, 1.19-1.35) at 65+. The predictive accuracies of all models were low, with the best performance (AUC 0.603) observed in Random Forest for predicting AD onset at age 65-69. INTERPRETATION: Although significant associations were identified between many risk factors and AD, the low predictive accuracies suggest that specialised healthcare diagnosis data is not sufficient for predicting AD and linkage with other data sources is needed.

Symptomatic and Preventive Medication Use before and after Alzheimer's Disease Diagnosis: A 10-Year Matched Cohort Study.

OBJECTIVE: To investigate longitudinal changes in symptomatic and preventive medication use among community-dwelling people with and without Alzheimer's disease (AD) 5 years pre- and post-AD diagnosis. DESIGN: Retrospective matched cohort study. SETTINGS AND PARTICIPANTS: The sample comprised 58,496 people with a geriatrician/neurologist-verified AD diagnosis matched 1:1 for age, sex, and region to people without AD in Finland. METHODS: Medication dispensing data were obtained from the Finnish Prescription Register. Prevalence of symptomatic and preventive medication use was evaluated every 6 months from 5 years pre- to post-AD diagnosis. Longitudinal changes in medication use between people with and without AD were compared using ordinal logistic regression. RESULTS: During the 5 years pre- and post-diagnosis, there were differences in symptomatic (P < .001) and preventive (P = .006) medication use between people with and without AD. Over the 5 years pre-diagnosis, prevalence of symptomatic and preventive medications increased in both people with and without AD. During the 1 year pre-diagnosis, people with AD had a higher increase in use of ≥3 symptomatic medications (+4.4% vs +2.2%) and ≥3 preventive medications (+6.4% vs +2.9%) compared to people without AD. Over the 5 years post-diagnosis, symptomatic medication use plateaued in both people with and without AD. Meanwhile, people using ≥3 preventive medications decreased (-6.0%) in those with AD, but increased (+6.1%) in those without AD. During the follow-up period, people with AD had a larger absolute percentage increase in prevalence of antipsychotics (+22.7% vs +1.8%) and antidepressants (+19.1% vs +5.0%) than people without AD. During the same period, paracetamol and calcium supplement use increased by 31.1% and 20.4%, respectively, among people with AD. The largest absolute percentage decrease in prevalence of preventive medications over the 5 years post-diagnosis were beta-blockers (-9.8%) and statins (-7.0%) in people with AD. CONCLUSIONS AND IMPLICATIONS: At the point of and following diagnosis, there were population-level changes in medication use among people with AD. Medication assessments during this period appear to coincide with discontinuation of preventive medications whereas minimal changes were observed in symptomatic medication use.

Statin use and the risk of Parkinson's disease in persons with diabetes: A nested case-control study.

AIMS: Persons with diabetes may have an elevated risk of Parkinson's disease (PD). Statin use could also modify the progression of PD. The aim was to study whether there is an association between statin exposure and risk of PD in persons with diabetes. METHODS: A nationwide, nested case-control study restricted to people with diabetes was performed as part of nationwide register-based Finnish study on PD (FINPARK). Study included 2017 PD cases and their 7934 matched controls without PD. Persons with PD were diagnosed between 1999 and 2015, and statin use (1995-2015) was determined from Prescription Register. In the main analysis, exposure at least 3 years before outcome was considered. Cumulative exposure was categorized into tertiles, and associations were analysed with conditional logistic regression (adjusted with comorbidities and number of antidiabetic drugs). RESULTS: Prevalence of statin use was similar in PD cases and controls, with 54.2% of cases and 54.4% controls exposed before the lag time (adjusted odds ratio [aOR] = 1.03; 95% confidence interval [CI]: 0.92-1.15). Those in the highest cumulative statin exposure tertile had higher risk of PD than statin nonusers (aOR = 1.22; 95% CI: 1.04-1.43), or those in the lowest cumulative statin exposure tertile (aOR = 1.29; 95% CI: 1.07-1.57). CONCLUSION: Our nationwide study that controlled for diabetes duration and used 3-year lag between exposure and outcome to account for reverse causality does not provide support for the hypothesis that statin use decreases the risk of PD.

Use of oral health care services among older home care clients in the context of an intervention study.

BACKGROUND: An increasing number of care-dependent older people living at home need external support to receive regular dental care. OBJECTIVES: To investigate the use of oral health care services among old home care clients who participated in an intervention study focusing on oral self-care and nutrition. MATERIALS AND METHODS: This study employed data from the multidisciplinary Nutrition, Oral Health and Medication (NutOrMed) intervention study with a population-based sample of 245 home care clients (74% female) aged 75 or more divided in intervention (n = 140) and two control groups (n = 105). The data were collected through interviews at baseline and 6-month follow-up. RESULTS: At baseline, 43% of participants reported visits to oral health care within the previous year. At 6-month follow-up, this proportion was 51%. In the intervention group, the corresponding figures were 46% and 53%, and in the controls 39% and 48%. Adjusted regression analyses showed that this change was statistically significant (p = 0.008). In addition, higher education and toothache or other discomfort related to teeth or dentures at baseline were associated with increased use after the 6-month follow-up (OR = 1.1, 95% CI = 1.0-1.2; OR = 3.4, 95% CI = 1.5-7.9) but being edentulous indicated the opposite (OR = 0.2, 95% CI = 0.1-0.4). Belonging to the intervention group was not associated with increased use. CONCLUSIONS: In older adults, any efforts to raise awareness of oral health are of great potential to increase use of services.

Prevalence of Cardiovascular Drugs and Oral Anticoagulant Use among Persons with and without Parkinson's Disease.

INTRODUCTION: Cardio- and cerebrovascular diseases are common among persons with Parkinson's disease (PD), but it is unknown how the prevalence of cardiovascular drug and oral anticoagulant use changes in relation to PD diagnosis. METHODS: We investigated the prevalence of cardiovascular drug and oral anticoagulant use among persons with and without PD among 17,541 persons who received incident PD diagnosis in 2001-2015 in Finland and their 116,829 matched comparison persons. Prevalence was calculated in 6-month time windows from 5 years before to 5 years after PD diagnosis (index date) and compared to a matched cohort without PD using generalized estimating equations. RESULTS: Persons with PD had higher prevalence of any cardiovascular drugs (unadjusted OR = 1.15; 95% CI: 1.11-1.18) and oral anticoagulants (unadjusted OR = 1.16; 95% CI: 1.11-1.22) before index date than those without PD. After index date, persons with PD had lower prevalence of cardiovascular drugs (0.94; 95% CI: 0.91-0.96), and no difference was observed for oral anticoagulants. Prevalence of any cardiovascular drugs on the index date was 66 and 61% for persons with and without PD, respectively. ß-blockers were the most common cardiovascular drugs in both cohorts. Warfarin was the most common oral anticoagulant, but the use of direct oral anticoagulants increased during the last years of follow-up. CONCLUSION: Orthostatic hypotension and weight loss likely explain the decreased cardiovascular drug use after PD diagnosis. Results with oral anticoagulants may reflect clinical assessment of benefits being larger than risks, despite the risks associated with their use in persons with PD.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

European position paper on polypharmacy and fall-risk-increasing drugs recommendations in the World Guidelines for Falls Prevention and Management: implications and implementation.

Falls prevention and management in older adults is a critical global challenge. One of the key risk factors for falls is the use of certain medications. Therefore, to prevent medication-related falls, the following is recommended in the recent World Guidelines for Falls Prevention and Management: (1) assess for fall history and the risk of falls before prescribing potential fall-risk-increasing drugs (FRIDs), (2) use a validated, structured screening and assessment tool to identify FRIDs when performing a medication review, (3) include medication review and appropriate deprescribing of FRIDs as a part of the multifactorial falls prevention intervention, and (4) in long-term care residents, if multifactorial intervention cannot be conducted due to limited resources, the falls prevention strategy should still always include deprescribing of FRIDs.In the present statement paper, the working group on medication-related falls of the World Guidelines for Falls Prevention and Management, in collaboration with the European Geriatric Medicine Society (EuGMS) Task and Finish group on FRIDs, outlines its position on how to implement and execute these recommendations in clinical practice.Preferably, the medication review should be conducted as part of a comprehensive geriatric assessment to produce a personalized and patient-centered assessment. Furthermore, the major pitfall of the published intervention studies so far is the suboptimal implementation of medication review and deprescribing. For the future, it is important to focus on gaining which elements determine successful implementation and apply the concepts of implementation science to decrease the gap between research and practice.

Therapeutic dilemma's: antipsychotics use for neuropsychiatric symptoms of dementia, delirium and insomnia and risk of falling in older adults, a clinical review.

PURPOSE: Because of the common and increasing use of antipsychotics in older adults, we aim to summarize the current knowledge on the causes of antipsychotic-related risk of falls in older adults. We also aim to provide information on the use of antipsychotics in dementia, delirium and insomnia, their adverse effects and an overview of the pharmacokinetic and pharmacodynamic mechanisms associated with antipsychotic use and falls. Finally, we aim to provide information to clinicians for weighing the benefits and harms of (de)prescribing. METHODS: A literature search was executed in CINAHL, PubMed and Scopus in March 2022 to identify studies focusing on fall-related adverse effects of the antipsychotic use in older adults. We focused on the antipsychotic use for neuropsychiatric symptoms of dementia, insomnia, and delirium. RESULTS: Antipsychotics increase the risk of falls through anticholinergic, orthostatic and extrapyramidal effects, sedation, and adverse effects on cardio- and cerebrovascular system. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antipsychotics without current indication. CONCLUSIONS: Deprescribing of antipsychotics should be considered and encouraged in older people at risk of falling, especially when prescribed for neuropsychiatric symptoms of dementia, delirium or insomnia. If antipsychotics are still needed, we recommend that the benefits and harms of antipsychotic use should be reassessed within two to four weeks of prescription. If the use of antipsychotic causes more harm than benefit, the deprescribing process should be started.

ß2-Adrenoceptor Agonists in Asthma or Chronic Obstructive Pulmonary Disease and Risk of Parkinson's Disease: Nested Case-Control Study.

Introduction: Although ß2-adrenoceptor (ß2AR) agonists have been associated with a lower risk of Parkinson's disease (PD), the findings are inconclusive and may reflect confounding by indication. We studied the association between inhaled ß2AR agonists and risk of PD in persons with asthma or chronic obstructive pulmonary disease (COPD). Methods: The nested case-control study was conducted within a register-based Finnish Parkinson's disease study (FINPARK) and included 1406 clinically verified PD cases diagnosed during 1999-2015, who also had asthma/COPD >3 years before PD. PD cases were matched with up to seven controls by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N = 8630). Cumulative and average annual exposure to short- and long-acting ß2AR agonists before a 3-year lag period was assessed with quartiles of defined daily doses (DDDs). Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression. Results: Cumulative exposure to either short- or long-acting ß2AR agonists was not associated with a risk of PD. With average annual exposure, a decreased risk was observed only for the highest quartile of long-acting ß2AR agonists (aOR 0.75; 95% CI 0.58-0.97). In the stratified analysis the lowest risk estimates were observed among those with both asthma and COPD diagnoses. The suggestion of an inverse association was seen for the highest quartile of long-acting ß2AR agonists in asthma. Discussion: Higher levels of exposure to ß2AR agonists were not consistently associated with a reduced risk of PD. The inverse association in the highest category of average annual exposure to long-acting ß2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.

Hospitalization and the Risk of Initiation of Antipsychotics in Persons With Parkinson's Disease.

OBJECTIVES: The use of antipsychotics in persons with Parkinson's disease (PD) is common, although their use may aggravate the symptoms of PD. Clozapine and quetiapine are the only antipsychotics recommended in PD treatment guidelines. Information on factors associated with initiation of antipsychotics is needed. We investigated whether recent hospitalization is associated with initiation of antipsychotics in persons with PD, and whether discharge diagnoses differ between those who had antipsychotics initiated and those who did not. DESIGN: Nested case-control study in the nationwide register-based Finnish Study on Parkinson's disease (FINPARK). SETTING AND PARTICIPANTS: The FINPARK study includes 22,189 persons who received an incident, clinically verified PD diagnosed during 1996-2015 and were community-dwelling at the time of diagnosis. The cases were 5088 persons who had antipsychotics initiated after PD diagnosis, identified with 1-year washout. The controls were 5088 age-, sex-, and time from PD diagnosis-matched persons who did not use antipsychotics on the matching date (antipsychotic purchase date). Recent hospitalization was defined as discharge in the 2-week period preceding the matching date. METHODS: Associations were investigated with conditional logistic regression. RESULTS: Quetiapine was the most commonly initiated antipsychotic (72.0% of cases), followed by risperidone (15.0%). Clozapine was initiated rarely (1.1%). Recent hospitalization associated strongly with antipsychotic initiation [61.2% of cases and 14.9% of controls, odds ratio (OR) 9.42, 95% CI 8.33-10.65], and longer hospitalizations were more common among cases. PD was the most common discharge diagnosis category (51.2% of hospitalized cases and 33.0% controls), followed by mental and behavioral disorders (9.3%) and dementia (9.0%) among cases. Antidementia and other psychotropic medication use were more common among cases. CONCLUSIONS AND IMPLICATIONS: These results suggest that antipsychotics were initiated because of neuropsychiatric symptoms or aggravation of those symptoms. Antipsychotics should be prescribed after careful consideration to avoid adverse effects in persons with Parkinson's disease.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Risk factors of pneumonia in persons with and without Alzheimer's disease: a matched cohort study.

BACKGROUND: Pneumonia is a very common infection in the cognitively impaired adult population, often leading to long-term deterioration, in physical and cognitive performance. Evidence is lacking on whether chronic comorbidities and drug use are risk factors for pneumonia in persons with Alzheimer's disease (AD). The objective of this study was to investigate the risk factors of pneumonia in community dwellers with and without AD. METHODS: We performed a retrospective register-based study utilizing the Medication Use and Alzheimer's disease (MEDALZ) cohort, which is based on Finnish nationwide healthcare registers and includes all community dwellers who received a verified clinical diagnosis of AD between 2005 to 2011. This study comprised 69,350 persons with AD and 69,350 persons without AD matched by age, gender, and region of residence. Association between comorbidities, drug use, and hospitalization due to pneumonia were assessed using Cox Regression. RESULTS: During the follow-up, 25.0% (n = 17,105) of the AD cohort and 15.8% (n = 10,966) of the non-AD cohort were hospitalized due to pneumonia. Persons with AD had a higher risk of pneumonia also after adjusting for comorbidities (HR 1.76, 95% CI 1.71-1.80). Previous pneumonia was the strongest risk factor for pneumonia in both cohorts. All comorbidities and drug use excluding biological product use were associated with a higher risk of pneumonia, but stronger associations were observed in the non-AD cohort. The risk of hospitalization following psychotropic drug use was proportional to the number of psychotropics utilized. CONCLUSIONS: Pneumonia is a serious, potentially life-threatening illness, and risk factors for pneumonia include several potentially avoidable drugs. In addition, good care of existing comorbidities might prevent pneumonia and related hospitalization.

Long-term exposure to low-level particulate air pollution and Parkinson's disease diagnosis - A Finnish register-based study.

BACKGROUND: There is mixed evidence for an association between particulate matter air pollution and Parkinson's disease despite biological plausibility. OBJECTIVES: We studied the association between particulate air pollution, its components and Parkinson's disease (PD) risk. METHODS: We conducted a nested case-control study within the population of Finland using national registers. A total of 22,189 incident PD cases diagnosed between 1996 and 2015 were matched by age, sex and region with up to seven controls (n = 148,009) per case. Time weighted average air pollution exposure to particulate matter and its components was modelled at the residential addresses, accounting for move history, for the 16 years preceding diagnosis. Conditional logistic regression analysis was used to evaluate the association between air pollution and PD. Different exposure periods (6-16 years, 11-16 years, 5-10 years, 0-5 years) before the index date (date of PD diagnosis) were applied. RESULTS: Time-weighted average exposures were relatively low at 12.1 ± 6.5 µg/m3 (mean ± SD) for PM10 and 7.7 ± 3.2 µg/m3 for PM2.5. No associations were found between PM2.5 or PM10 exposure 6-16 years before index date and PD (OR: 0.99; 95% CI: 0.96, 1.02; per IQR of 3.9 µg/m3 and OR: 0.99; 95% CI: 0.96, 1.01; per IQR of 7.8 µg/m3, respectively). However, inverse associations were observed for the same exposure period with black carbon (OR: 0.96; 95% CI: 0.93, 0.99; per IQR of 0.6 µg/m3), sulphate (OR: 0.79; 95% CI: 0.68, 0.92; per IQR of 1.2 µg/m3), secondary organic aerosols (OR: 0.86; 95% CI: 0.80, 0.93; per IQR of 0.1 µg/m3) and sea salt (OR: 0.92; 95% CI: 0.87, 0.98; per IQR of 0.1 µg/m3). DISCUSSION: Low-level particulate matter air pollution was not associated with increased risk of incident PD in this Finnish nationwide population. The observed weak inverse associations with specific particle components should be investigated further.

Incidence and outcomes of head injuries in people with and without Parkinson disease.

BACKGROUND AND PURPOSE: Fall-related injuries are a major health concern among people with Parkinson disease (PD). We compared the incidence and postinjury mortality of head injuries and traumatic brain injury (TBI) among persons with and without PD. METHODS: This register-based study was conducted on the FINPARK cohort, which includes 22,189 persons who were diagnosed with PD in Finland during 1996-2015. We excluded persons with a previous head injury, leaving 20,514 persons with PD. For each person with PD, 1-7 matching persons without PD and previous head injury were identified with respect to age, sex, and residence. The Cox proportional hazard model was used to estimate hazard ratios for head injury. A logistic regression model was used to compare mortality. RESULTS: Persons with PD had 2.16-fold (95% confidence interval [CI] = 2.06-2.26) risk of all head injuries and 1.97-fold (95% CI = 1.84-2.10) risk of TBI after adjustment for age, sex, and comorbidities. Persons with PD had higher 1-year mortality after any type of head injury (adjusted odds ratio [aOR] = 1.44, 95% CI = 1.28-1.62), TBI (aOR = 1.33, 95% CI = 1.14-1.57), or non-TBI head injury (aOR = 1.72, 95% CI = 1.42-2.07) than persons without PD. The higher risk of mortality was observed 6 months after TBI and 1 month after non-TBI injury in persons with PD. Persons with PD and head injury also had higher 1-year mortality than persons with PD and without head injury. CONCLUSIONS: Persons with PD have a higher risk of head injury and higher postinjury mortality than persons without PD.

High anticholinergic burden and hyposalivation and xerostomia in the elderly.

OBJECTIVE: The aim was to study the association between high anticholinergic burden and hyposalivation and xerostomia among older people. BACKGROUND: Anticholinergic drugs have been shown to cause xerostomia and hyposalivation. Yet there are few studies on the association between anticholinergic burden and hyposalivation and xerostomia in the elderly. MATERIAL AND METHODS: The study population consisted of community-dwelling older people (n = 321, mean age 81.6 years) from the Oral health GeMS study. Participants provided salivary samples and xerostomia was determined with a questionnaire. The baseline data were collected by interviews, oral clinical examinations and from patient records. Each participant's anticholinergic burden was determined by eight anticholinergic scales. Poisson regression models with robust error variance were used to estimate relative risks (RR) with a 95% confidence interval (CI). RESULTS: RRs of high anticholinergic burden in anticholinergic scales for xerostomia (multiple symptoms) ranged from 1.02 to 1.68; for low unstimulated salivary flow (≤0.1 mL/min) from 1.47 to 1.67; and for low stimulated salivary flow (≤0.7 mL/min) from 0.99 to 2.07. A high anticholinergic burden according to seven out of eight scales was associated (p < .05) with hyposalivation or xerostomia. CONCLUSIONS: A high anticholinergic burden was associated more strongly with hyposalivation (both unstimulated and stimulated) than with xerostomia.

The Cumulative Use of Muscle Relaxants and the Risk of Alzheimer's Disease: A Nationwide Case-Control Study.

BACKGROUND: Use of pharmacological treatments is one possible modifiable risk factor for cognitive disorders. OBJECTIVE: To investigate if the use of muscle relaxants is associated with the risk of Alzheimer's disease (AD). METHODS: The study was performed in a nested case-control design. Altogether 70,718 community-dwelling residents of Finland who received AD diagnosis in 2005-2011 were included as cases (the MEDALZ study). Each case was matched with four controls without AD by age, sex, and region of residence (N = 282,858). Data was extracted from Prescription register (1995-2012), Special Reimbursement register (1972-2012), and Hospital Discharge register (1972-2012). Drug use periods were modeled with PRE2DUP-method. Defined daily dose (DDD) was used to quantify the use. Analyses were conducted for any muscle relaxant use, and drug specific analyses were done for orphenadrine and tizanidine. A five-year lag window prior to the diagnosis was used, and results analyzed with conditional logistic regression. RESULTS: The use of any muscle relaxant was associated with the risk of AD, aOR (95% CI) 1.04 (1.02-1.07). Stronger associations were observed with longer use (>366 days, aOR 1.12 (1.03-1.21)) than shorter use (1-365 days aOR, 1.04 (1.02-1.06)) compared to non-users. Dose-response was not observed. Tizanidine was not associated with AD, whereas cumulative exposure of orphenadrine (≥101 DDDs) was associated with the risk of AD, aOR 1.19 (1.07-1.32). CONCLUSION: Muscle relaxant use was associated with the risk of AD and higher exposure to orphenadrine showed increased risk. Further studies on higher doses and longer durations of use are warranted.