Pre-diagnostic presentations of Multiple System Atrophy case control study in a primary care dataset

Background: We here report the pre-diagnostic clinical presentations of patients with Multiple System Atrophy (MSA) from analysis of a large routine clinical care database. Methods: Data were extracted from a primary care database in the German healthcare system for the period between January 2000 and December 2020. We identified 250 patients with new diagnosis of MSA and 250 controls matched for age, sex, and index year. Logistic regression analyses were conducted to assess association between MSA and predefined diagnoses. Results: The greatest rate increase in the 2 years preceding diagnosis of MSA was seen for hypotension and balance impairment but rates of memory problems, urinary dysfunction, dizziness and depression rates were also markedly increased, and ataxia was solely identified in those with a later diagnosis of MSA. Up to 5 years before diagnosis similar patterns were seen, but >5 years before diagnosis only depression rates were increased with a trend for increase in constipation. Conclusions: Presentations that were significantly more common in patients with MSA in the pre-diagnostic phase than in controls were autonomic complaints such as postural hypotension, urinary and bowel dysfunction, and early balance impairment. However, the study also highlights that memory complaints and depression may be early features of MSA years before diagnosis

Widening the Spectrum of Risk Factors, Comorbidities, and Prodromal Features of Parkinson Disease

Importance: The prodromal phase of Parkinson disease (PD) may last for more than 10 years. Recognition of the spectrum and occurrence of risk factors, comorbidities, and prodromal features of PD can increase understanding of the causes and development of the disease and help identify individuals at risk. Objective: To identify the association of a subsequent diagnosis of PD with a range of risk factors and prodromal features, including lifestyle factors, comorbidities, and potential extracerebral manifestations of PD. Design, Setting, and Participants: This was a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2011, and December 31, 2020. Included were patients with incident diagnosis of PD without a previous diagnosis of parkinsonism or dementia and controls matched 1:2 for age, sex, region, and earliest year of outpatient encounter. Exposures: Exposures were selected based on previous systematic reviews, case-control and cohort studies reporting on risk factors, comorbidities, and prodromal features of PD. Main Outcomes and Measures: Previously postulated risk factors and prodromal features of PD, using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coding. Results: A total of 138 345 patients with incident PD (mean [SD] age, 75.1 [9.8] years; 73 720 male [53.3%]) and 276 690 matched controls (mean [SD] age, 75.1 (9.8) years; 147 440 male [53.3%]) were identified. Study participants were followed up for a mean (SD) of 6.0 (2.0) years. Consistent with previous reports, risk factors and prodromal features associated with PD included traumatic brain injury, odds ratio (OR), 1.62; 95% CI, 1.36-1.92; alcohol misuse, OR, 1.32; 95% CI, 1.21-1.44; hypertension, OR, 1.29; 95% CI, 1.26-1.31; anosmia, OR, 2.16; 95% CI, 1.59-2.93; and parasomnias (including RBD), OR, 1.62; 95% CI, 1.42-1.84. In addition, there were associations with restless legs syndrome (OR, 4.19; 95% CI, 3.91-4.50), sleep apnea (OR, 1.45; 95% CI, 1.37-1.54), epilepsy (OR, 2.26; 95% CI, 2.07-2.46), migraine (OR, 1.21; 95% CI, 1.12-1.29), bipolar disorder (OR, 3.81; 95% CI, 3.11-4.67), and schizophrenia (OR, 4.48; 95% CI, 3.82-5.25). The following diagnoses were also found to be associated with PD: sensory impairments beyond anosmia, such as hearing loss (OR, 1.14; 95% CI, 1.09-1.20) and changes of skin sensation (OR, 1.31; 95% CI, 1.21-1.43). There were also positive associations with skin disorders (eg, seborrheic dermatitis, OR, 1.30; 95% CI, 1.15-1.46; psoriasis, OR, 1.13; 95% CI, 1.05-1.21), gastrointestinal disorders (eg, gastroesophageal reflux, OR, 1.29; 95% CI, 1.25-1.33; gastritis, OR, 1.28; 95% CI, 1.24-1.33), conditions with a potential inflammatory component (eg, seronegative osteoarthritis, OR, 1.21; 95% CI, 1.03-1.43), and diabetes types 1 (OR, 1.32; 95% CI, 1.21-1.43) and 2 (OR, 1.24; 95% CI, 1.20-1.27). Associations even 5 to 10 years before diagnosis included tremor (odds ratio [OR], 4.49; 95% CI, 3.98-5.06), restless legs syndrome (OR, 3.73; 95% CI, 3.39-4.09), bipolar disorder (OR, 3.80; 95% CI, 2.82-5.14), and schizophrenia (OR, 4.00; 95% CI, 3.31-4.85). Conclusions and Relevance: Results of this case-control study suggest that the associations found between PD and certain risk factors, comorbidities, and prodromal symptoms in a representative population may reflect possible early extrastriatal and extracerebral pathology of PD. This may be due to shared genetic risk with PD, medication exposure, or direct causation, or represent pathophysiologically relevant factors contributing to the pathogenesis of PD

Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment

In healthy older adults, resveratrol supplementation has been shown to improve long-term glucose control, resting-state functional connectivity (RSFC) of the hippocampus, and memory function. Here, we aimed to investigate if these beneficial effects extend to individuals at high-risk for dementia, i.e., patients with mild cognitive impairment (MCI). In a randomized, double-blind interventional study, 40 well-characterized patients with MCI (21 females; 50–80 years) completed 26 weeks of resveratrol (200 mg/d; n = 18) or placebo (1,015 mg/d olive oil; n = 22) intake. Serum levels of glucose, glycated hemoglobin A1c and insulin were determined before and after intervention. Moreover, cerebral magnetic resonance imaging (MRI) (3T) (n = 14 vs. 16) was conducted to analyze hippocampus volume, microstructure and RSFC, and neuropsychological testing was conducted to assess learning and memory (primary endpoint) at both time points. In comparison to the control group, resveratrol supplementation resulted in lower glycated hemoglobin A1c concentration with a moderate effect size (ANOVARM p = 0.059, Cohen's d = 0.66), higher RSFC between right anterior hippocampus and right angular cortex (p < 0.001), and led to a moderate preservation of left anterior hippocampus volume (ANOVARM p = 0.061, Cohen's d = 0.68). No significant differences in memory performance emerged between groups. This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c, preserves hippocampus volume, and improves hippocampus RSFC in at-risk patients for dementia. Larger trials with longer intervention time should now determine if these benefits can be validated and extended to cognitive function

Factors Associated with Non-Severe Adverse Reactions after Vaccination against SARS-CoV-2: A Cohort Study of 908,869 Outpatient Vaccinations in Germany

Background: Vaccination against SARS-CoV-2 significantly reduces the transmissibility of the virus and the likelihood of a severe course of COVID-19, and is thus a critical component in overcoming the current pandemic. The factors associated with adverse reactions after vaccination against SARS-CoV-2 have not yet been sufficiently evaluated. Methods: We used the Disease Analyzer database (IQVIA) to identify 531,468 individuals who received a total of 908,869 SARS-CoV-2 vaccinations in 827 general practices in Germany between April and September 2021. Cox regression models were used to analyze the frequency of vaccination-related side effects reported within 14 days after SARS-CoV-2 vaccination, as well as subjects’ demographic characteristics and comorbidities. Results: The total number of side effects documented was 28,287 (3.1% of all vaccinations). Pain in the limb (24.3%), fatigue (21.0%), dizziness (17.9%), joint pain (15.7%), fever (9.5%), nausea (7.5%), and myalgia (6.4%) were the most common side effects documented among the 12,575 vaccinations with definite side effects. In the multivariate regression analysis, young age was associated with much higher odds of reported side effects (OR18–30 years: 4.45, OR31–40 years: 3.50, OR41–50 years: 2.89). In addition, pre-existing comorbidities such as dementia (OR: 1.54), somatoform disorder (OR: 1.53), anxiety disorder (OR: 1.43), depression (OR: 1.37), chronic respiratory tract disease (OR: 1.27), hypertension (OR: 1.20), and obesity (1.14) significantly increased the odds of side effects. Finally, the male sex was associated with increased odds of reported side effects (OR: 1.17). Conclusion: Our study, based on a large outpatient database from Germany, identified young age, male sex, and pre-existing comorbidities such as dementia, somatoform disorders, anxiety disorders, and depression as factors associated with vaccine-related adverse events diagnosed in GP practices. These data could help to identify subgroups needing particular advice and care in the context of SARS-CoV-2 vaccinations

What have we learned in the past year? A study on pharmacy purchases of psychiatric drugs from wholesalers in the days prior to the first and second COVID-19 lockdowns in Germany

International audienceNo study has yet investigated how the second coronavirus disease (COVID-19) lockdown has impacted the consumption of psychiatric medications in Germany. Therefore, the goal of this study was to analyze weekly pharmacy purchases of psychiatric drugs from wholesalers in this country in 2019 and 2020 using data from the IMS RPM® (Regional Pharmaceutical Market) Weekly Database. The outcome was the number of pharmacy purchases of psychiatric drugs per week from wholesalers between Calendar Week 2 and Calendar Week 52 in 2019 and 2020. Calendar Weeks 12 and 51 in 2020 corresponded to the days prior to the first and second German COVID-19 lockdowns, respectively. Descriptively, compared with 2019, the number of weekly pharmacy purchases of psychiatric drugs increased by 32% between Calendar Weeks 2–11 and Calendar Week 12 in 2020, while there was a 9% increase between Calendar Weeks 13–50 and Calendar Week 51 that same year. Overall, the relative increase in the weekly pharmacy purchases of psychiatric drugs from wholesalers was less pronounced before the second COVID-19 lockdown in Germany than before the first. Further studies are warranted to identify factors (e.g., decreases in panic buying) that may have contributed to this decreasing trend

The long-term impact of the COVID-19 pandemic on primary and specialized care provision and disease recognition in Germany

Background The COVID-19 pandemic and the imposed lockdowns severely affected routine care in general and specialized physician practices. Objective To describe the long-term impact of the COVID-19 pandemic on the physician services provision and disease recognition in German physician practices and perceived causes for the observed changes. Design Observational study based on medical record data and survey data of general practitioners and specialists' practices. Participants 996 general practitioners (GPs) and 798 specialist practices, who documented 6.1 million treatment cases for medical record data analyses and 645 physicians for survey data analyses. Main measures Within the medical record data, consultations, specialist referrals, hospital admissions, and documented diagnoses were extracted for the pandemic (March 2020–September 2021) and compared to corresponding pre-pandemic months in 2019. The additional online survey was used to assess changes in practice management during the COVID-19 pandemic and physicians' perceived main causes of affected primary and specialized care provision. Main results Hospital admissions (GPs: −22% vs. specialists: −16%), specialist referrals (−6 vs. −3%) and recognized diseases (−9 vs. −8%) significantly decreased over the pandemic. GPs consultations initially decreased (2020: −7%) but compensated at the end of 2021 (+3%), while specialists' consultation did not (−2%). Physicians saw changes in patient behavior, like appointment cancellation, as the main cause of the decrease. Contrary to this, they also mentioned substantial modifications of practice management, like reduced (nursing) home visits (41%) and opening hours (40%), suspended checkups (43%), and delayed consultations for high-risk patients (71%). Conclusion The pandemic left its mark on primary and specialized healthcare provision and its utilization. Both patient behavior and organizational changes in practice management may have caused decreased and non-compensation of services. Evaluating the long-term effect on patient outcomes and identifying potential improvements are vital to better prepare for future pandemic waves

Zeitliche Veränderung der Prävalenz von Parkinson-Diagnosen in Deutschen Hausarzt- und Neurologischen Praxen von 2010 bis 2019 // Trends in Prevalence of Parkinson’s Disease in German General and Neurological Practices from 2010 to 2019

Hintergrund Bis 2040 wird mit einer erheblichen Prävalenzzunahme der Parkinson-Erkrankung und damit einhergehend mit einer erheblichen Belastung der Versorgungssysteme gerechnet. Ziel der Studie war es deshalb, eine Veränderung der Anzahl an Parkinson-Patienten bereits im Zeitraum 2010 bis 2019 in deutschen Haus- und neurologischen Facharztpraxen zu untersuchen. Methode Die vorliegende Querschnittstudie basiert auf den Daten von 411 Hausarzt- (HA) und 56 neurologischen Facharzt-Praxen (FA) aus der IQVIA Disease Analyzer Datenbank. Die Anzahl der etablierten und neu diagnostizierten Patienten mit Parkinson-Erkrankung wurde in den Jahren 2010 und 2019 mit Alters- und Geschlechtsstruktur und der Anteil therapierten Patienten untersucht.Ergebnisse Die Zahl der Parkinson-Patienten veränderte sich geringfügig zwischen 2010 bis 2019 von 3352 (0,36% aller Patienten) auf 3541 (0,33%) in den HA-Praxen und von 4976 (3,48%) auf 4826 (3,34%) in den FA-Praxen. Die Anzahl der neu diagnostizierten Fälle fiel bei den HA-Praxen leicht von 862 (0,09% aller Patienten) auf 836 (0,08%) und bei den FA-Praxen von 1818 (1,27%) auf 1372 (0,95% aller Patienten). Der Anteil an Frauen unter allen Parkinson-Erkrankten sank sowohl in HA- und FA- Praxen von 52,0% bzw. 50,2% auf 47,3% bzw. 46,0%. Das Durchschnittsalter stieg bei den HA-Praxen von 77,1 (SD 10,4) im Jahr 2010 auf 77,7 (SD 9,3) Jahre im Jahr 2019 und in FA-Praxen von 74,6 (SD 9,9) auf 75,8 (SD 9,9) Jahre. Diskussion Die prognostizierte Zunahme von Parkinson-Patienten in der ambulanten Versorgung lässt sich für den Zeitraum 2010 bis 2019 nicht bestätigen. Es gab jedoch eine Verschiebung der Altersstruktur zu höheren Altersgruppen und eine Verringerung des Anteils an Frauen mit einer Parkinson-Erkrankung. Neben ätiologischen Erklärungen sollten Besonderheiten des Versorgungssystems und methodische Limitationen berücksichtigt werden

No significant association between COVID-19 diagnosis and the incidence of depression and anxiety disorder? A retrospective cohort study conducted in Germany

International audienceLittle is known about the effects of coronavirus disease 2019 (COVID-19) on mental health compared with other respiratory infections. Thus, the aim of this retrospective cohort study was to investigate whether COVID-19 diagnosis is associated with a significant increase in the incidence of depression and anxiety disorder in patients followed in general practices in Germany compared with acute upper respiratory infection diagnosis. This study included all patients diagnosed with symptomatic or asymptomatic COVID-19 for the first time in 1198 general practices in Germany between March 2020 and May 2021. Patients diagnosed with acute upper respiratory infection were matched to those with COVID-19 using propensity scores based on sex, age, index month, and Charlson Comorbidity Index. The index date corresponded to the date on which either COVID-19 or acute upper respiratory infection was diagnosed. Differences in the incidence of depression and anxiety disorder between the COVID-19 and the acute upper respiratory infection group were studied using conditional Poisson regression models. This study included 56,350 patients diagnosed with COVID-19 and 56,350 patients diagnosed with acute upper respiratory infection (52.3% women; mean [SD] age 43.6 [19.2] years). The incidence of depression (IRR = 1.02, 95% CI = 0.95–1.10) and anxiety disorder (IRR = 0.94, 95% CI = 0.83–1.07) was not significantly higher in the COVID-19 group than in the upper respiratory infection group. Compared with acute upper respiratory infection diagnosis, COVID-19 diagnosis was not associated with a significant increase in the incidence of depression and anxiety disorder in patients treated in general practices in Germany