Sources of PM2.5 exposure misclassification in three Finnish register-based study populations and the impact on attenuation of health effect estimates.

Air pollution is a leading environmental health risk factor. The risk estimates, primarily based on air pollution epidemiology, are sensitive to exposure misclassification, which can result in underestimation. To address some of these challenges, our aim is to investigate how the length of the period over which the exposure is averaged, trends in long-term PM2.5 concentrations, and the seasonal variability are associated with each other. Furthermore, we assess the impact of residential relocation on exposure levels and quantify random exposure misclassification due to modelling and its impact on the attenuation of effects with respect to averaging time. We used nested air quality modelling across Finland, gridded population, and address histories from three study populations: the MATEX pregnancy and preschool children cohorts, as well as the FINPARK study's individuals diagnosed with Parkinson's disease and their controls, to estimate PM2.5 exposures. The prediction error was estimated by comparing modelled concentrations to observations and by using previous estimates for random monitoring instrument error. Due to the decreasing trend in PM2.5 concentrations, exposure levels rose progressively with longer averaging times, increasing by up to 28 % over a 16-year period. The shorter the exposure period, the more pronounced the seasonal effects: pregnant mothers' trimester-specific exposures were 13-22 % higher for trimesters ending in spring and 10-16 % lower for those ending in autumn compared to the average for the entire pregnancy. Residential relocation had a relatively minor impact on the exposure levels of the preschool children and adult FINPARK study population, but this effect was possibly partly masked by the decreasing trend. The results indicated that using predicted concentrations led to random exposure misclassification and potentially attenuated health effects. This effect became more notable when increasing the length of the exposure period from 3 months to 5 years, doubling the underestimation ratio from 1.5 to 3.1.

Identifying Comorbidity Patterns in People with and without Alzheimer's Disease Using Latent Dirichlet Allocation.

Background: Multimorbidity is common in older adults and complicates diagnosing and care for this population. Objective: We investigated co-occurrence patterns (clustering) of medical conditions in persons with Alzheimer's disease (AD) and their matched controls. Methods: The register-based Medication use and Alzheimer's disease study (MEDALZ) includes 70,718 community-dwelling persons with incident AD diagnosed during 2005-2011 in Finland and a matched comparison cohort. Latent Dirichlet Allocation was used to cluster the comorbidities (ICD-10 diagnosis codes). Modeling was performed separately for AD and control cohorts. We experimented with different numbers of clusters (also known as topics in the field of Natural Language Processing) ranging from five to 20. Results: In both cohorts, 17 of the 20 most frequent diagnoses were the same. Based on a qualitative assessment by medical experts, the cluster patterns were not affected by the number of clusters, but the best interpretability was observed in the 10-cluster model. Quantitative assessment of the optimal number of clusters by log-likelihood estimate did not imply a specific optimal number of clusters. Multidimensional scaling visualized the variability in cluster size and (dis)similarity between the clusters with more overlapping of clusters and variation in group size seen in the AD cohort. Conclusions: Early signs and symptoms of AD were more commonly clustered together in the AD cohort than in the comparison cohort. This study experimented with using natural language processing techniques for clustering patterns from an epidemiological study. From the computed clusters, it was possible to qualitatively identify multimorbidity that differentiates AD cases and controls.

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.

Changes in Stress Urinary Incontinence Symptoms after Pelvic Organ Prolapse Surgery: a Nationwide Cohort Study (FINPOP).

INTRODUCTION AND HYPOTHESIS: Various strategies are employed to manage stress urinary incontinence (SUI) during pelvic organ prolapse (POP) surgery. This study was aimed at facilitating shared decision-making by evaluating SUI symptom changes, staged SUI procedures, and their prognostic factors following POP surgery without concomitant SUI intervention. METHODS: We analyzed 2,677 POP surgeries from a population-based observational cohort, excluding patients with prior SUI surgery. The outcome measures were subjective SUI utilizing the Pelvic Floor Distress Inventory-20 questionnaire and number of subsequent SUI procedures. Multivariable linear models were applied to identify predictors of persistent SUI, procedures for persistent SUI, and de novo SUI. The primary assessment occurred at the 2-year follow-up. RESULTS: At baseline, 50% (1,329 out of 2,677) experienced SUI; 35% (354 out of 1,005) resolved, an additional 14% (140 out 1,005) improved, and 5.1% (67 out of 1,308) underwent a procedure for persistent SUI. De novo SUI symptoms developed in 20% (218 out of 1,087), with 3.2% (35 out of 1,087) reporting bothersome symptoms; 0.8% (11 out of 1,347) underwent a procedure for de novo SUI. High baseline symptom severity increased the risk of persistent SUI (adjusted odds ratio [aOR] 2.04, 95% confidence interval [CI] 1.65-2.53), whereas advanced preoperative apical prolapse decreased the risk (aOR 0.89, 95% CI 0.85-0.93). De novo SUI was more common with advancing age (aOR 1.03, 95% CI 1.01-1.05), baseline urgency urinary incontinence (aOR 1.21, 95% CI 1.06-1.38), and after transvaginal mesh surgery (aOR 1.93, 95% CI 1.24-3.00). It was not dependent on the compartment or preoperative degree of prolapse. CONCLUSIONS: In a pragmatic setting, POP surgery results in a low rate of subsequent SUI procedures.

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.

Agreement between physician- and patient-reported Canadian cardiovascular society scores among patients undergoing elective coronary angiography-The CATS study.

The primary aim of revascularization in stable coronary artery disease (CAD) is symptom relief. The severity of symptoms is usually evaluated by the physician, not by the patient. We examined the agreement between physician- and patient-reported Canadian Cardiovascular Society (CCS) scores among patients scheduled for elective coronary angiography in a cross-sectional study. Patients (n = 650) and cardiologists evaluated the severity of angina symptoms by filling the CCS questionnaire before coronary angiography. Patients were divided into those without CAD (stenosis diameter <50%, n = 445) and those with CAD (stenosis diameter >50%, n = 205). CAD patients were further divided into three groups according to disease severity (single-, double- or triple-vessel disease). The mean age of the patients was 67.6 (9.9) years and 50.6% were women. In 51.8% (95% CI 44.5%-59.0%) of patients with CAD and 51.9% (95% CI 47.0%-56.8%) of those without, physician- and patient reported CCS scores agreed. The physician reported better CCS scores in 33.9% (95% CI 27.6%-40.7%) of patients with CAD and 36.2% (95% CI 31.8%-41.0%) of patients without CAD. The proportions of full or partial agreement between physician- and patient reported CCS scores were similar across the CAD severity groups. To summarize, we observed a significant discrepancy between the physician- and patient-reported symptom severity in patients with or without CAD scheduled for angiography. The physician underestimated the symptoms in third of the cases. Thus, patient-reported symptom severity, rather than physician's evaluation, should be the cornerstone of treatment decisions.

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.

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.

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.

Diagnostic groups of hospital stays and outpatient visits during 10 years before Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a major determinant of healthcare costs and increase in the healthcare service use occur already before the AD diagnosis. However, little is known how the different diagnosis categories contribute to this increase in healthcare use. We investigated how the hospitalizations and specialized healthcare outpatient visits from different diagnosis categories, based on the International Classification of Diseases (ICD-10) chapters, contribute to increased specialized healthcare service use during ten-year period preceding AD diagnosis. METHODS: A register-based nationwide cohort of 42,934 community-dwelling persons who received clinically verified AD diagnosis in between 2008 and 2011 in Finland and 1:1 age, sex and hospital district- matched comparison cohort were included. Hospitalizations and specialized healthcare visits were categorized by the main diagnosis, according to the ICD-10 chapters. AD and dementia were separated to their own category. The number of persons with visits and stays was calculated for every 6 months, irrespective of the frequency of visits/stays individual had during that time window. Furthermore, the relative distribution of the diagnosis categories was computed. RESULTS: AD cohort was more likely to have visits and stays during the 10-year period (OR 1.19, 95% CI 1.17-1.21). The number of persons with visits and stays peaked in AD cohort from 1.5 years before the diagnosis when the differences in relative distribution of different diagnosis categories also became evident. The largest differences were observed for visits/stays with cognitive disorders, symptoms of unspecified diseases and psychiatric disorders diagnoses, and those with missing diagnosis codes in the last time window before AD diagnosis. CONCLUSIONS AND IMPLICATIONS: Increased healthcare service use before AD diagnosis does not seem to arise from differences in specific diagnosis categories of ICD-10 such as diseases of the circulatory system, but from the higher frequency of visits and stays among persons with AD across diagnosis categories. Based on the relative distribution of diagnosis categories, the steep increase in healthcare service use just before and during the diagnostic process is likely due to prodromal symptoms and visits related to cognition.

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).

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.

Finding Answers.

In this narrative medicine essay, a pharmacoepidemiologist worries that her brother's lifelong neurological challenges may have been caused by a heritable genetic variant and that she possibly passed it to her young son, who looks uncannily like his uncle.

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.