Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.

Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI. METHODS: In 30 patients with the diagnosis of MCI (16 female, 14 male; age, 70 +/- 8 y), baseline and follow-up examinations (mean observation period, 16 mo) were performed. In all patients, the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET. Individual PET data were screened for findings suggestive of Alzheimer's disease (AD), with the help of an automated computer program. After stereotactical normalization of the PET images, this program performs an observer-independent statistical comparison with an age-matched reference database (n = 22). RESULTS: In 43% of all MCI subjects, a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline (PET+); 57% of all MCI patients were carriers of the APOE epsilon4 allele (e4+). In 40% of all patients, progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation. Statistical evaluation revealed the best results for PET with regard to early diagnosis of DAT in MCI patients (sensitivity, 92%; specificity, 89%). Classification according to the APOE genotype was significantly less successful (sensitivity, 75%; specificity, 56%). However, a combination of both diagnostic tests allowed early diagnosis with either very high specificity (PET+ AND e4+: sensitivity, 67%; specificity, 100%) or very high sensitivity (PET+ OR e4+: sensitivity, 100%; specificity, 44%). CONCLUSION: (18)F-FDG PET of cerebral glucose metabolism is a valuable diagnostic tool for the prediction of clinical outcome in individual MCI patients. Results are superior to the exclusive assessment of the APOE genotype. A combination of both functional imaging and genotyping may allow an early high-risk or low-risk stratification of patients with either very high sensitivity or very high specificity. This may be valuable, for example, for patient selection in scientific studies.     

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.     

Associations between Nighttime Traffic Noise and Sleep: The Finnish Public Sector Study

Background: Associations between traffic noise and sleep problems have been detected in experimental studies, but population-level evidence is scarce.Objectives: We studied the relationship between the levels of nighttime traffic noise and sleep disturbances and identified vulnerable population groups.Methods: Noise levels of nighttime–outdoor traffic were modeled based on the traffic intensities in the cities of Helsinki and Vantaa, Finland. In these cities, 7,019 public sector employees (81% women) responded to postal surveys on sleep and health. We linked modeled outdoor noise levels to the residences of the employees who responded to the postal survey. We used logistic regression models to estimate associations of noise levels with subjectively assessed duration of sleep and symptoms of insomnia (i.e., difficulties falling asleep, waking up frequently during the night, waking up too early in the morning, nonrestorative sleep). We also used stratified models to investigate the possibility of vulnerable subgroups.Results: For the total study population, exposure to levels of nighttime–outside (L_{night, outside}) traffic noise > 55 dB was associated with any insomnia symptom ≥ 2 nights per week [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.05, 1.65]. Among participants with higher trait anxiety scores, which we hypothesized were a proxy for noise sensitivity, the ORs for any insomnia symptom at exposures to L_{night, outside} traffic noises 50.1–55 dB and > 55 dB versus ≤ 45 dB were 1.34 (95% CI: 1.00, 1.80) and 1.61 (95% CI: 1.07, 2.42), respectively.Conclusions: Nighttime traffic noise levels > 50 dB L_{night, outside} was associated with insomnia symptoms among persons with higher scores for trait anxiety. For the total study population, L_{night, outside} > 55 dB was positively associated with any symptoms.     

Results of metal-on-metal hip resurfacing in patients 40 years old and younger

The prevalence of total hip arthroplasty in young patients is small but increasing. We analyzed the results of metal-on-metal hip resurfacing (MMHR) in patients aged 40 years or less. In total 74 operations were performed on 64 patients. Mean age at operation was 33.2 years. HHS averaged 92.3 points at latest follow-up, mean UCLA activity was 8.2. Patients with comorbidity evinced lower scores in HHS, in UCLA activity and in quality of life than patients without comorbidities. Eight revisions (10.8 %) were performed, of which seven due to adverse reaction to metal debris. Seven-year survival was 90.5 %. The functional outcome of hip resurfacing in this cohort was excellent, but overall survival was unsatisfactory. Further analysis is required to verify the role of hip resurfacing among young and active patients.     

Life satisfaction and pain interference in spine surgery patients before and after surgery: comparison between on-opioid and opioid-naïve patients

Quality of Life Research - Pain has a negative impact on life satisfaction (LS). Our primary aims were to compare LS in on-opioid and opioid-naïve spine surgery patients and to evaluate...     

Convergence model for effectual prevention and control of zoonotic diseases: a health system study on ‘One Health’ approach in Ahmedabad,India

The complexity and increasing burden of zoonotic diseases create challenges for the health systems of developing nations. Public health systems must therefore be prepared to face existing and future disease threats at the human–animal interface. The key for this is coordinated action between the human and the animal health systems. Although some studies deal with the question of how these two systems interact during unforeseen circumstances such as outbreaks, a dearth of literature exists on how these systems interact on early detection, prevention and control of zoonotic diseases; assessing this problem from the health system perspective in a developing nation adds further complexity. Systems thinking is one of the promising approaches in understanding the factors that influence the system’s complexity and dynamics of health maintenance. Therefore, this study aims to understand the generic structure and complexity of interaction between these actors within the domain of One Health for the effectual prevention and control of zoonotic diseases in India.The present study will be executed in Ahmedabad, located on the Western part of India, in Gujarat state, using a mixed methods approach. For the first step, zoonotic diseases will be prioritised for the local context through semi-quantitative tools. Secondly, utilising semi-structured interviews, stakeholders from the human and animal health systems will be identified and ranked. Thirdly, the identified stakeholders will be questioned regarding the current strength of interactions at various levels of the health system (i.e. managerial, provider and community level) through a quantitative network survey. Fourthly, utilising a vignette method, the ideal convergence strategies will be documented and validated through policy Delphi techniques. Finally, through a participatory workshop, the factors that influence convergence for the control and prevention of zoonotic diseases will be captured.This study will provide a comprehensive picture of the current strength of collaboration and network depth at various levels of the health system. Further, it will assist different actors in identifying the relevance of possible One Health entry points for participation, i.e. it will not only contribute but will also develop a system convergence model for the effectual prevention and control of zoonotic diseases.