COVID-19 in cancer patients: The impact of vaccination on outcomes early in the pandemic.

BACKGROUND: With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID-19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID-19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll-out and to identify risk factors associated with hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. METHODS: We performed a retrospective cohort study of cancer patients with COVID-19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. RESULTS: Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID-19, severe COVID-19, and 30-day COVID-19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID-19 but with no impact on hospitalization or mortality due to COVID-19. CONCLUSION: Our study highlights a significant benefit of COVID-19 vaccination for cancer patients-specifically its protection against severe COVID-19.

The impact of the COVID-19 pandemic on hospital-acquired infections at a comprehensive cancer center.

BACKGROUND: Robust infection prevention and control (IPC) measures were deployed across health care institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment, enhanced contact precautions, and an emphasis on hand hygiene. Here, we evaluate the effect of enhanced IPC practices on the occurrence of various hospital-associated infections (HAIs) in a comprehensive cancer center. METHODS: From September 2016 through March 2022, we calculated the incidence rates (IRs) of HAIs for C. difficile infection, multidrug-resistant organisms, respiratory viral infections (RVIs), and device-related infections. We analyzed the incidence rate ratios for all HAIs during the periods before the pandemic, during the pandemic, at the time of the surges, and in COVID-19-designated wards. RESULTS: When comparing the prepandemic to the pandemic period, the IR across all MRDOs was similar. We observed a decrease in the IR of central line-associated bloodstream infections and a stable IR of catheter-associated urinary tract infections. A significant decrease was observed in the IR of C. difficile infection. The total IR of nosocomial RVIs decreased, as did for each respiratory virus. A similar IR of nosocomial RVIs between COVID-19 community surge versus nonsurge periods was observed except for SARS-CoV-2, RSV, and influenza. multidrug resistant organisms were 5 times more likely to occur on the COVID-19 wards compared with the non-COVID-19 wards. CONCLUSIONS: Implementing strict IPC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs.

Nosocomial COVID-19 at a comprehensive cancer center during the first year of the pandemic: Lessons learned.

BACKGROUND: The spread of coronavirus disease 2019 (COVID-19) in health care settings endangers patients with cancer. As knowledge of the transmission of COVID-19 emerged, strategies for preventing nosocomial COVID-19 were updated. We describe our early experience with nosocomial respiratory viral infections (RVIs) at a cancer center in the first year of the pandemic (March 2020-March 2021). METHODS: Nosocomial RVIs were identified through our infection control prospective surveillance program, which conducted epidemiologic investigations of all microbiologically documented RVIs. Data was presented as frequencies and percentages or medians and ranges. RESULTS: A total of 35 of 3944 (0.9%) documented RVIs were determined to have been nosocomial acquired. Majority of RVIs were due to SARS CoV-2 (13/35; 37%) or by rhinovirus/enterovirus (12/35; 34%). A cluster investigation of the first 3 patients with nosocomial COVID-19 determined that transmission most likely occurred from employees to patients. Five patients (38%) required mechanical ventilation and 4 (31%) died during the same hospital encounter. CONCLUSIONS: Our investigation of the cluster led to enhancement of our infection control measures. The implications of COVID-19 vaccination on infection control policies is still unclear and further studies are needed to delineate its impact on the transmission of COVID-19 in a hospital setting.

Association Between Primary Care Practitioner Empathy and Risk of Cardiovascular Events and All-Cause Mortality Among Patients With Type 2 Diabetes: A Population-Based Prospective Cohort Study.

PURPOSE: To examine the association between primary care practitioner (physician and nurse) empathy and incidence of cardiovascular disease (CVD) events and all-cause mortality among patients with type 2 diabetes. METHODS: This was a population-based prospective cohort study of 49 general practices in East Anglia (United Kingdom). The study population included 867 individuals with screen-detected type 2 diabetes who were followed up for an average of 10 years until December 31, 2014 in the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care (ADDITION)-Cambridge trial. Twelve months after diagnosis, patients assessed practitioner empathy and their experiences of diabetes care during the preceding year using the consultation and relational empathy (CARE) measure questionnaire. CARE scores were grouped into tertiles. The main outcome measures were first recorded CVD event (a composite of myocardial infarction, revascularization, nontraumatic amputation, stroke, and fatal CVD event) and all-cause mortality, obtained from electronic searches of the general practitioner record, national registries, and hospital records. Hazard ratios (HRs) were estimated using Cox models adjusted for relevant confounders. The ADDITION-Cambridge trial is registered as ISRCTN86769081. RESULTS: Of the 628 participants with a completed CARE score, 120 (19%) experienced a CVD event, and 132 (21%) died during follow up. In the multivariable model, compared with the lowest tertile, higher empathy scores were associated with a lower risk of CVD events (although this did not achieve statistical significance) and a lower risk of all-cause mortality (HRs for the middle and highest tertiles, respectively: 0.49; 95% CI, 0.27-0.88, P = .01 and 0.60; 95% CI, 0.35-1.04, P = .05). CONCLUSIONS: Positive patient experiences of practitioner empathy in the year after diagnosis of type 2 diabetes may be associated with beneficial long-term clinical outcomes. Further work is needed to understand which aspects of patient perceptions of empathy might influence health outcomes and how to incorporate this understanding into the education and training of practitioners.

The association between psychosocial factors and change in lifestyle behaviour following lifestyle advice and information about cardiovascular disease risk.

BACKGROUND: Physical activity (PA) and fruit and vegetable intake (FVI) are two key modifiable risk factors for cardiovascular disease (CVD). Achieving change in these behaviours is challenging and affected by many variables including psychosocial factors. We aimed to investigate the association between social support, stress and mood, and change in PA and FVI following provision of CVD risk information and web-based lifestyle advice. METHODS: Seven hundred sixteen blood donors (56% male; mean age 57 years) from the intervention arms of the Information and Risk Modification (INFORM) trial, a randomised controlled trial to assess the impact of providing CVD risk and web-based lifestyle information, were analysed as a prospective cohort. We used linear and logistic regression analyses to quantify the association between social support, stress and mood at baseline and behaviour change following the intervention. We modelled objective (average acceleration measured by Axivity AX3 wrist-worn accelerometers and plasma carotenoid levels) and subjective (self-reported recreational PA and FVI) outcomes as change between baseline and 12 weeks follow-up. RESULTS: There was no clear association between social support and change in objective or subjective PA. Higher levels of stress and, to a lesser extent, depression symptoms were associated with smaller improvement in self-reported PA (ß -1.53 h/week vigorous PA, 95% confidence interval (CI) -2.30 to -0.75, p < 0.001 for stress; ß -1.64 h/week, 95% CI -3.50 to 0.21, p = 0.082 for little interest). Higher social support was associated with greater odds and higher stress was associated with lower odds of increasing self-reported FVI to five portions per day (odds ratio (OR) 1.33, 95% CI 1.05 to 1.69, p = 0.020 for social support; OR 0.57, 95% CI 0.43 to 0.76, p < 0.001 for stress). The associations between psychosocial factors and objective FVI were not statistically significant. CONCLUSIONS: High stress and low mood may reduce the likelihood and extent of reported change in PA and FVI following CVD risk information and advice. Greater social support may be associated with increased FVI. The role of psychosocial factors should be considered when developing, tailoring and evaluating future interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17721237 . Registered 12 January 2015.

Detection of Dementia Cases in Two Swedish Health Registers: A Validation Study.

BACKGROUND: Population-based health registers are potential assets in epidemiological research; however, the quality of case ascertainment is crucial. OBJECTIVE: To compare the case ascertainment of dementia, from the National Patient Register (NPR) and the Cause of Death Register (CDR) with dementia diagnoses from six Swedish population based studies. METHODS: Sensitivity, specificity, and positive predictive value (PPV) of dementia identification in NPR and CDR were estimated by individual record linkage with six Swedish population based studies (n = 19,035). Time to detection in NPR was estimated using data on dementia incidence from longitudinal studies with more than two decades of follow-up. RESULTS: Barely half of the dementia cases were ever detected by NPR or CDR. Using data from longitudinal studies we estimated that a record with a dementia diagnosis appears in the NPR on average 5.5 years after first diagnosis. Although the ability of the registers to detect dementia cases was moderate, the ability to detect non-dementia cases was almost perfect (99%). When registers indicate that there is a dementia diagnosis, there are very few instances in which the clinicians determined the person was not demented. Indeed, PPVs were close to 90%. However, misclassification between dementia subtype diagnoses is quite common, especially in NPR. CONCLUSIONS: Although the overall sensitivity is low, the specificity and the positive predictive value are very high. This suggests that hospital and death registers can be used to identify dementia cases in the community, but at the cost of missing a large proportion of the cases.

Screening for type 2 diabetes: do screen-detected cases fare better?

AIMS/HYPOTHESIS: We aimed to investigate whether diabetes cases detected through screening have better health outcomes than clinically detected cases in a population-based cohort of adults who were eligible to be screened for diabetes at 10 year intervals. METHODS: The Västerbotten Intervention Programme is a community- and individual-based public health programme in Västerbotten County, Sweden. Residents are invited to clinical examinations that include screening for diabetes by OGTTs at age 30, 40, 50 and 60 years (individuals eligible for screening, n = 142,037). Between 1992 and 2013, we identified 1024 screen-detected cases and 8642 clinically detected cases of diabetes using registry data. Clinically detected individuals were either prior screening participants (n = 4506) or people who did not participate in screening (non-participants, n = 4136). Study individuals with diabetes were followed from date of detection until end of follow-up, emigration, death or incident cardiovascular disease (CVD), renal disease or retinopathy event, and compared using Cox proportional hazard regression adjusted for calendar time, age at detection, year of detection, sex and socioeconomic status. RESULTS: The average age at diabetes diagnosis was 4.6 years lower for screen-detected individuals compared with clinically detected individuals. Overall, those who were clinically detected had worse health outcomes than those who were screen-detected (HR for all-cause mortality 2.07 [95% CI 1.63, 2.62]). Compared with screen-detected study individuals, all-cause mortality was higher for clinically detected individuals who were screening non-participants (HR 2.31 [95% CI 1.82, 2.94]) than for those clinically detected who were prior screening participants (HR 1.70 [95% CI 1.32, 2.18]). Estimates followed a similar pattern for CVD, renal disease and retinopathy. CONCLUSIONS/INTERPRETATION: Individuals with screen-detected diabetes were diagnosed earlier and appeared to fare better than those who were clinically detected with regard to all-cause mortality, CVD, renal disease and retinopathy. How much of these associations can be explained by earlier treatment because of screening rather than healthy user bias, lead time bias and length time bias warrants further investigation.

Change in lifestyle behaviors and diabetes risk: evidence from a population-based cohort study with 10 year follow-up.

BACKGROUND: Promoting positive changes in lifestyle behavior in the whole population may be a feasible and effective approach to reducing type 2 diabetes burden, but the impact of population shifts of modifiable risk factors remains unclear. Currently most of the evidence on modifiable lifestyle behavior and type 2 diabetes risk on a population level comes from studies of between-individual differences. The objective of the study was to investigate the association and potential impact on disease burden for within-individual change in lifestyle behavior and diabetes risk. METHODS: Population-based prospective cohort study of 35,680 participants aged 30-50 at baseline in 1990-2003 in Västerbotten County, Sweden (follow-up until 2013). Five self-reported modifiable lifestyle behaviors (tobacco use, physical activity, alcohol intake, dietary fiber intake and dietary fat intake) were measured at baseline and 10 year follow-up. Lifestyle behaviors were studied separately, and combined in a score. Incident diabetes was detected by oral glucose tolerance tests. Multivariate logistic regression models and population attributable fractions (PAF) were used to analyze the association between change in lifestyle behavior between baseline and 10 year follow-up, and risk of incident diabetes. RESULTS: Incident diabetes was detected in 1,184 (3.3%) participants at 10 year follow-up. There was a reduced diabetes risk associated with increase in dietary fiber intake, odds ratio (OR) 0.79 (95% confidence interval (CI) 0.66, 0.96) for increase of at least one unit standard deviation (3.0 g/1,000 kcal) of the baseline distribution, PAF 16.0% (95% CI 4.2, 26.4%). Increase in the lifestyle behavior score was associated with reduced diabetes risk, OR 0.92 (95% CI 0.85, 0.99) per unit increase of the score. CONCLUSIONS: These results support a causal link between lifestyle behavior and type 2 diabetes incidence. A small shift in lifestyle behaviors, in particular intake of dietary fiber, has the potential to reduce diabetes burden in the population and might be a suitable target for public health intervention.

Impact of weight maintenance and loss on diabetes risk and burden: a population-based study in 33,184 participants.

BACKGROUND: Weight loss in individuals at high risk of diabetes is an effective prevention method and a major component of the currently prevailing diabetes prevention strategies. The aim of the present study was to investigate the public health potential for diabetes prevention of weight maintenance or moderate weight loss on a population level in an observational cohort with repeated measurements of weight and diabetes status. METHODS: Height, weight and diabetes status were objectively measured at baseline and 10 year follow-up in a population-based cohort of 33,184 participants aged 30-60 years between 1990 and 2013 in Västerbotten County, Sweden. The association between risk of incident diabetes and change in BMI or relative weight was modelled using multivariate logistic regression. Population attributable fractions (PAF) were used to assess population impact of shift in weight. RESULTS: Mean (SD) BMI at baseline was 25.0 (3.6) kg/m2. Increase in relative weight between baseline and follow-up was linearly associated with incident diabetes risk, odds ratio (OR) 1.05 (95% confidence interval (CI) 1.04-1.06) per 1% change in weight. Compared to weight maintenance (±1.0 kg/m2), weight gain of > +1.0 kg/m2 was associated with an increased risk of incident diabetes, OR 1.52 (95% CI 1.32, 1.74), representing a PAF of 21.9% (95% CI 15.8, 27.6%). For moderate weight loss (-1.0 to -2.0 kg/m2) the OR was 0.72 (95% CI 0.52, 0.99). CONCLUSIONS: Weight maintenance in adulthood is strongly associated with reduced incident diabetes risk and there is considerable potential for diabetes prevention in promoting this as a whole population strategy.

Personality traits and the risk for Parkinson disease: a prospective study.

In this study, we explored the association between the personality traits, neuroticism and introversion, and risk of Parkinson disease (PD). A population-based cohort study was conducted using questionnaire data from the Swedish Twin Registry for twins born 1926-1958 (n > 29,000). Personality traits were assessed in 1973 by a short form of Eysenck's Personality Inventory. The cohort was followed from 1974 to 2012 through Swedish patient and cause of death registers for PD ascertainment. Cox proportional hazards regression was used to estimate subsequent risk of PD, adjusting for attained age, sex and smoking. A mediation analysis was performed to further explore the role of smoking in the relationship between personality trait and PD. Confounding by familial factors was explored using a within-pair analysis. During a mean follow-up time of 36.8 years, 197 incident PD cases were identified. Both neuroticism and introversion were associated with an increased risk of PD after adjustment. Smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk. In the within-pair analyses, associations for neuroticism and introversion were attenuated. In conclusion, our study provides evidence that neuroticism is associated with an increased risk of PD that is in part suppressed by smoking. There was a weak association between introversion and PD and this effect was at least partly mediated through smoking. The observed effects may partly be explained by familial factors shared by twins.

The Participation of HPV-Vaccinated Women in a National Cervical Screening Program: Population-Based Cohort Study.

BACKGROUND: Concerns have been raised that HPV-vaccination might affect women's cervical screening behavior. We therefore investigated the association between opportunistic HPV-vaccination and attendance after invitation to cervical screening. METHODS: A cohort of all women resident in Sweden, born 1977-1987 (N=629,703), and invited to cervical screening, was followed October 2006 - December 2012. Invitations to screening were identified via the National Quality Register for Cervical Cancer Prevention, as was the primary outcome of a registered smear. Vaccination status was obtained from two nationwide health data registers. Hazard ratios (HR) were estimated using Cox regression adjusted for age, education level and income (HRadj). Women were individually followed for up to 6 years, of which the first and second screening rounds were analyzed separately. RESULTS: Screening attendance after three years of follow-up was 86% in vaccinated women (N=4,897) and 75% in unvaccinated women (N=625,804). The crude HR of screening attendance in vaccinated vs. unvaccinated women was 1.31 (95% CI 1.27-1.35) in the first screening round. Adjustment for education and income reduced but did not erase this difference (HRadj=1.09, 95% CI 1.05-1.13). In the second screening round, attendance was likewise higher in HPV-vaccinated women (crude HR=1.26, 95% CI 1.21-1.32; HRadj=1.15, 95% CI 1.10-1.20). CONCLUSIONS: HPV-vaccination is so far associated with equal or higher attendance to cervical screening in Sweden in a cohort of opportunistically vaccinated young women. Most but not all of the difference in attendance was explained by socioeconomic differences between vaccinated and unvaccinated women. HPV vaccine effectiveness studies should consider screening attendance of HPV-vaccinated women when assessing incidence of screen-detected cervical lesions.

Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial.

BACKGROUND: Extracranial carotid and vertebral artery dissection is an important cause of stroke, especially in young people. In some observational studies it has been associated with a high risk of recurrent stroke. Both antiplatelet drugs and anticoagulant drugs are used to reduce risk of stroke but whether one treatment strategy is more effective than the other is unknown. We compared their efficacy in the Cervical Artery Dissection in Stroke Study (CADISS), with the additional aim of establishing the true risk of recurrent stroke. METHODS: We did this randomised trial at hospitals with specialised stroke or neurology services (39 in the UK and seven in Australia). We included patients with extracranial carotid and vertebral dissection with onset of symptoms within the past 7 days. Patients were randomly assigned (1:1) by an automated telephone randomisation service to receive antiplatelet drugs or anticoagulant drugs (specific treatment decided by the local clinician) for 3 months. Patients and clinicians were not masked to allocation, but investigators assessing endpoints were. The primary endpoint was ipsilateral stroke or death in the intention-to-treat population. The trial was registered with EUDract (2006-002827-18) and ISRN (CTN44555237). FINDINGS: We enrolled 250 participants (118 carotid, 132 vertebral). Mean time to randomisation was 3·65 days (SD 1·91). The major presenting symptoms were stroke or transient ischaemic attack (n=224) and local symptoms (headache, neck pain, or Horner's syndrome; n=26). 126 participants were assigned to antiplatelet treatment versus 124 to anticoagulant treatment. Overall, four (2%) of 250 patients had stroke recurrence (all ipsilateral). Stroke or death occurred in three (2%) of 126 patients versus one (1%) of 124 (odds ratio [OR] 0·335, 95% CI 0·006-4·233; p=0·63). There were no deaths, but one major bleeding (subarachnoid haemorrhage) in the anticoagulant group. Central review of imaging failed to confirm dissection in 52 patients. Preplanned per-protocol analysis excluding these patients showed stroke or death in three (3%) of 101 patients in the antiplatelet group versus one (1%) of 96 patients in the anticoagulant group (OR 0·346, 95% CI 0·006-4·390; p=0·66). INTERPRETATION: We found no difference in efficacy of antiplatelet and anticoagulant drugs at preventing stroke and death in patients with symptomatic carotid and vertebral artery dissection but stroke was rare in both groups, and much rarer than reported in some observational studies. Diagnosis of dissection was not confirmed after review in many cases, suggesting that radiographic criteria are not always correctly applied in routine clinical practice. FUNDING: Stroke Association.

Occupational complexity and risk of Parkinson's disease.

BACKGROUND: The etiology of Parkinson's disease (PD) remains unclear, and environmental risk-factors such as occupation have attracted interest. OBJECTIVE: The goal was to investigate occupational complexity in relation to PD. METHODS: We conducted a population-based cohort study based on the Swedish Twin Registry that included 28,778 twins born between 1886 and 1950. We identified 433 PD cases during the study period. Data on occupation were collected from either the 1970 or 1980 Swedish census, and occupational complexity was assessed via a job exposure matrix. Cox proportional hazard regression analyses with age as the underlying time scale were used to assess PD risk as a function of the three domains of occupational complexity: data, people, and things. Sex and smoking were included as covariates. Analyses stratified by twin pair were conducted to test for confounding by familial factors. RESULTS: High occupational complexity with data and people was associated with increased risk overall (Hazard Ratio [HR]  = 1.07, 95% confidence interval [CI] 1.02-1.14, and HR = 1.10, 95% CI 1.01-1.21, respectively), and in men (HR = 1.08, 95% CI 1.01-1.16, and HR = 1.15, 95% CI 1.03-1.28, respectively). Complexity with things was not associated with risk of PD. When the analyses were stratified by twin pair, the HRs for occupational complexity with data and people were attenuated in men. CONCLUSIONS: High complexity of work with data and people is related to increased risk of PD, particularly in men. The attenuation of risk observed in the twin pair-stratified analyses suggests that the association may partly be explained by familial factors, such as inherited traits contributing to occupational selection or other factors shared by twins.

Evidence for modest familial co-aggregation between dementia and parkinsonism.

To investigate the contribution of shared familial risk to the co-occurrence of dementia and parkinsonism by studying familial co-aggregation of Alzheimer's disease (AD) and Parkinson's disease (PD). Using Swedish population-based registers we constructed two cohorts; a first-degree relative cohort of persons born 1932-1960 (n = 2,775,332) and a spouse cohort of persons born 1890-1960 (n = 4,736,006). Study persons were followed up between 1969 and 2009 in the National Patient and Cause of Death Registers. We modeled the association between incidence of disease and having at least one affected relative using Cox proportional hazard regression that estimated hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex and number of relatives. Within each disorder; dementia, AD, parkinsonian disorders and PD, there was a strong association between risk of disease and having at least one affected sibling or parent. There was also a modest shared familial risk between the diseases; risk of parkinsonian disorders was associated with having a sibling with AD (HR 1.35, 95% CI 1.11-1.65) and risk of dementia was associated with having a sibling with PD (HR 1.20, 95% CI 1.02-1.41). There were no meaningful familial risks among spouses. The risk of co-occurring dementia in PD was considerably increased (HR 2.83, 95% CI 2.76-2.89). There is strong familial aggregation within dementia, AD, parkinsonian disorders and PD, and modest familial co-aggregation between dementia and parkinsonism. Thus, co-occurrence of dementia and parkinsonism is not primarily caused by shared familial risk between AD and PD.

Familial coaggregation of Alzheimer's disease and Parkinson's disease: systematic review and meta-analysis.

BACKGROUND: Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families. METHODS: The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively. RESULTS: We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias. CONCLUSIONS: There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD.

Head injury and Parkinson's disease: a population-based study.

BACKGROUND: The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent. METHODS: We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date. RESULTS: Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment. CONCLUSIONS: Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD.

Accuracy and sensitivity of Parkinsonian disorder diagnoses in two Swedish national health registers.

BACKGROUND: Swedish population-based national health registers are widely used data sources in epidemiological research. Register-based diagnoses of Parkinson's disease have not been validated against clinical information. METHODS: Parkinson's disease (PD) and other parkinsonian disorder diagnoses were ascertained in two registers, i.e. the National Patient Register (NPR) and the Cause of Death Register (CDR). Diagnoses were validated in terms of accuracy (positive predictive value) and sensitivity against data from a population-based study of PD in 1998-2004 that screened more than 35,000 persons and identified 194 cases of parkinsonian disorders including 132 PD cases (the gold standard for the purposes of this study). RESULTS: Accuracy for any parkinsonian disorder diagnoses was 88.0% in the NPR and 94.4% in the CDR. Accuracy of PD diagnoses was 70.8% in the NPR and 66.7% in the CDR. Misclassification between differential parkinsonian diagnoses was common. The accuracy of PD diagnoses in the NPR improved to 83.0% by restricting the definition to primary diagnoses only. The sensitivity of PD diagnoses in the NPR and CDR combined was 83.1%, with a mean time to detection of 6.9 years. CONCLUSIONS: Population-based national health registers are valid data sources in epidemiological studies of PD or parkinsonian disorder etiology but are less suitable in studies of incidence or prevalence.

Genome-wide and gene-based association implicates FRMD6 in Alzheimer disease.

Genome-wide association studies (GWAS) that allow for allelic heterogeneity may facilitate the discovery of novel genes not detectable by models that require replication of a single variant site. One strategy to accomplish this is to focus on genes rather than markers as units of association, and so potentially capture a spectrum of causal alleles that differ across populations. Here, we conducted a GWAS of Alzheimer disease (AD) in 2,586 Swedes and performed gene-based meta-analysis with three additional studies from France, Canada, and the United States, in total encompassing 4,259 cases and 8,284 controls. Implementing a newly designed gene-based algorithm, we identified two loci apart from the region around APOE that achieved study-wide significance in combined samples, the strongest finding being for FRMD6 on chromosome 14q (P = 2.6 × 10(-14)) and a weaker signal for NARS2 that is immediately adjacent to GAB2 on chromosome 11q (P = 7.8 × 10(-9)). Ontology-based pathway analyses revealed significant enrichment of genes involved in glycosylation. Results suggest that gene-based approaches that accommodate allelic heterogeneity in GWAS can provide a complementary avenue for gene discovery and may help to explain a portion of the missing heritability not detectable with single nucleotide polymorphisms (SNPs) derived from marker-specific meta-analysis.

Occupational exposure in parkinsonian disorders: a 43-year prospective cohort study in men.

BACKGROUND: Several occupations and occupational exposures have been investigated for associations with Parkinson's disease. Common findings are increased risk associated with pesticide exposure and no association between Parkinson's disease and welding. METHODS: We explored the association between a broad range of possible occupational risk factors and Parkinson's disease as well as Parkinson's disease plus other forms of Parkinsonism (referred to as Parkinsonian disorders), using prospectively collected data in the population-based Swedish Twin Registry. A cohort of 14,169 Swedish men was followed for up to 43 years. We identified 234 Parkinsonian disorder cases including 204 Parkinson's disease cases with complete data. We assessed exposure to 14 chemical and biological compounds through a job exposure matrix. Hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking, and education were used to estimate the relative risk of disease associated with exposure. RESULTS: Exposure to inorganic dust was associated with increased risk of Parkinson's disease and Parkinsonian disorders, HR 1.6 (95% CI 1.1-2.4) and 1.5 (1.0-2.2) respectively. There was no association between Parkinson's disease or Parkinsonian disorders and occupational exposure to pesticides, welding smoke, metal dust, wood dust, animal handling, stone and concrete dust, chrome and nickel dust, quartz dust, organic dust, oil, asbestos, organic solvents and irritating gas. CONCLUSIONS: Inorganic dust should be explored further as a potential risk factor for Parkinson's disease. Occupational exposure to pesticides and twelve other compounds explored in this study may not be associated with risk of Parkinson's disease in Swedish men.

Serial re-challenge with influenza vaccine as a tool to study individual immune responses.

With new treatments of inflammatory diseases targeting key inflammatory pathways follows an increased risk for infections. The aim of the present study was to identify an immunological readout where consecutive immunizations induce reproducible immune responses. Such a method could be used as a tool to assess drug-induced immunomodulation in individual patients by comparing responses to the immunizations before and after introduction of a specific treatment. Importantly, the vaccine is merely used as a model antigen and protective immunity is not the primary aim of the method. Eleven volunteers were immunized with influenza vaccine three times, four weeks apart. In order to find the optimal readout for the method, immune responses to the immunizations were measured as circulating antigen-specific B-cells, serum antibody titers and avidity, T-cell proliferation and cytokine secretion. The first exposure to the influenza vaccine induced a stronger B- and T-cell responses than the consecutive immunizations. The second and third immunizations induced comparable but lower B-cell responses as measured by ELISPOT. In summary, we have measured immune responsiveness by using repeated immunizations with influenza virus vaccine as the model antigen. The induction of comparable B-cell responses after the second and third serial immunizations provides a possibility to investigate effects on immune responsiveness by immunomodulatory drugs. The method also allows humoral memory and immune competence per se to be studied on a cellular level in different patient groups.