Serum cholesterol during 27 years: assessment of systematic error and affecting factors and their role in interpreting population trends

BACKGROUND: The aim was to assess which factors cause a systematic error in serum total cholesterol measurements and how bias can influence the interpretation of serum cholesterol changes of the Finnish population. METHODS: Data on precision and accuracy during 27 years for serum total cholesterol were documented from participation in 438 rounds of five different external quality assessment (EQA) programs. RESULTS: The mean annual accuracy (bias) of the cholesterol assay using the results from all EQAs during 1978-2004 was -0.74% (95%CI -0.88 to -0.60). An exceptionally large deviation in bias coincided with the introduction of a new serum calibrator lot. New methods or instrumentation had only a minor impact on serum cholesterol bias. The mean serum cholesterol bias during the latest five population studies in 1982-2002 was -0.10% (95%CI -0.60 to 0.40) but comparison of the bias between the last study (CDC EQA in 2002) and the four previous ones (WHO EQA) showed a net difference of 3.32% (p<0.001). Correcting the mean serum cholesterol of men with respect to WHO and CDC EQA bias changed the interpretation for the last two survey years from an increase of 1.8% to no change. CONCLUSIONS: It is necessary to participate in EQA programs, which include target values measured by the CDC cholesterol reference method and then to perform bias corrections on the mean cholesterol values of the populations.     

Adoption of new antiglaucoma drugs in Finland: impact of changes in copayment

BACKGROUND: Copayments are common measures intended to control drug expenditures and promote rational prescribing. In Finland, new antiglaucoma drugs start with a high copayment, but once sufficient clinical experience is available, they are reevaluated and can receive a lower copayment status. OBJECTIVE: This study assessed the effect of changes in copayment level on the adoption of 2 antiglaucoma drugs. METHODS: A retrospective analysis was performed from 1997 to 2001 using the Finnish national register of reimbursed drug purchases, which covers approximately 98% of all antiglaucoma drug purchases in the country. There were 172,293 purchases of dorzolamide (plain or combined with timolol) and 281,377 purchases of latanoprost. An interrupted time-series design from approximately 30 months before and 20 months after the change in copayment was used in the analysis. The main outcome measures were the numbers of defined daily doses (DDDs) purchased and the monthly numbers of patients who purchased the study drugs for the first time before and after the change in copayment. RESULTS: A substantial increase in consumption of both dorzolamide and latanoprost was seen immediately after the introduction of the lower copayment. The monthly consumption of dorzolamide was 60,713 DDDs higher and the monthly consumption of latanoprost was 49,330 DDDs higher than expected according to the utilization trend during the higher copayment period. Twelve months later, the observed consumption of dorzolamide was 109% higher and that of latanoprost was 21% higher than if the copayment had remained the same. The number of new patients using the study drugs peaked within 2 months of the lower copayment, but the amount consumed per patient per day remained quite stable. CONCLUSIONS: Decreasing the copayment of a new antiglaucoma drug to the same level as the copayments of alternative drugs accelerated the adoption of these new products in Finland.     

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person‐years of exposure to warfarin‐only and 60,253 years of exposure to warfarin‐with‐statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin‐with‐statin compared to warfarin‐only and to allow multiple episodes per patient and time‐dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable‐adjusted RR = 0.98, 95% CI 0.89–1.07) or to simvastatin (RR = 1.01, 95% CI 0.91–1.11) with warfarin compared to exposure to warfarin‐only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.     

Dimensions of psychotic experiences among women in the general population

Full‐information factor analysis of ordinal data was employed to determine the factorial structure of the responses of 31,822 adult Swedish women to the 20 “positive” psychotic experience items of the Community Assessment of Psychic Experiences (CAPE) questionnaire. Five separable but correlated trait dimensions were found, reflecting Paranoia, Grandiosity, Magical Thinking, Delusions, and Hallucinations. High scores on any dimension were associated with a higher probability of questionnaire‐assessed lifetime major depressive episodes or generalized anxiety disorder, though Grandiosity was so only to a very small degree. Our results closely match previous findings among adolescents and young women, and demonstrate that psychotic experiences cannot be considered a single trait. Copyright © 2013 John Wiley & Sons, Ltd.     

Schizophrenia and pregnancy: a national register-based follow-up study among Finnish women born between 1965 and 1980

Archives of Women's Mental Health - To assess psychosocial and somatic risk factors related to pregnancy, and pregnancy-related complications or disorders in women with schizophrenia compared...     

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.     

Trichothecene mycotoxins activate NLRP3 inflammasome through a P2X7 receptor and Src tyrosine kinase dependent pathway

Inflammasome is an intracellular molecular platform of the innate immunity that is a key mediator of inflammation. The inflammasome complex detects pathogens and different danger signals, and triggers cysteine protease caspase-1-dependent processing of pro-inflammatory cytokines IL-1β, and IL-18 in dendritic cells and macrophages. Previously, we have shown that water-damaged building associated trichothecene mycotoxins, including roridin A, trigger IL-1β and IL-18 secretion in human macrophages. However, the molecular basis as well as mechanism behind this trichothecene-induced cytokine secretion has remained uncharacterized. Here, we show that the trichothecene-induced IL-1β secretion is dependent on NLRP3 inflammasome in human primary macrophages. Pharmacological inhibition and small interfering RNA approach showed that the trichothecene-induced NLRP3 inflammasome activation is mediated through ATP-gated P2X₇ receptor. Moreover, we show that trichothecene-triggered NLRP3 inflammasome activation is dependent on Src tyrosine kinase activity. In addition, gene silencing of c-Cbl, a negative autophagy-related regulator of c-Src, resulted in enhanced secretion of IL-1β and IL-18 in response to trichothecene mycotoxin stimulation in human macrophages. In conclusion, our results suggest that roridin A, a fungal trichothecene mycotoxin, acts as microbial danger signals that trigger activation of NLRP3 inflammasome through P2X₇R and Src tyrosine kinase signaling dependent pathway in human primary macrophages.     

Dental esthetics and quality of life in adults with severe malocclusion before and after treatment

Objective:To investigate the association between satisfaction with dental esthetics and quality of life, and esthetics satisfaction in relation to esthetic evaluations of three panel groups.Materials and Methods:Fifty-two patients (36 women, 16 men; age 18–61 years) with severe malocclusion were treated in Oulu University Hospital. Of these, 38 and 14 patients underwent orthodontic/surgical treatment and orthodontic treatment, respectively. A questionnaire and dental photographs were collected before and after treatment. The 14-item Oral Health Impact Profile (OHIP-14) was used to measure oral health-related quality of life. Satisfaction with dental esthetics was evaluated using the Visual Analogue Scale. Dental photographs were presented to three panel groups: 30 laypersons, 30 dental students, and 10 orthodontists, who rated the photographs using the Aesthetic Component of the Index of Orthodontic Treatment Need.Results:Oral health–related quality of life (OHIP-14 severity score) and esthetic satisfaction (according to the Visual Analogue Scale) improved after the treatment (P < .001). The most unsatisfied patients reported oral effects more often both before and after treatment. Changes in oral health–related quality of life components of severity, psychological discomfort, and psychological disability correlated positively with the changes in esthetic satisfaction. Orthodontists graded the situation before treatment as worse and the outcome as better than the laypersons; the level of grading by dental students fell between these two groups.Conclusion:Improvement in esthetic satisfaction due to the treatment of severe malocclusion improves oral health–related quality of life, particularly by decreasing psychological discomfort and psychological disability.