195 research outputs found
Unexpectedly High Prevalence of Common Variable Immunodeficiency in Finland
Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency. Prevalence varies greatly between countries and studies. Most diagnostic criteria include hypogammaglobulinemia and impaired vaccine response. Aim: To evaluate the minimum prevalence as well as the clinical and immunological phenotypes of CVID in Southern Finland. Methods: We performed a cross-sectional study to assess all adult CVID patients followed up in three hospital districts in Southern and South-Eastern Finland between April 2007 and August 2015. CVID diagnosis was based, with a minor modification, on the ESID/PAGID criteria for primary CVID. Antipolysaccharide responses to Pneumovax (R) were defined as impaired only if 50% or more of the serotypes did not reach a level of 0.35 mu g/mL after vaccination. We further characterized the patients' B cell phenotypes and complications associated with CVID. Results: In total, 9 patients were excluded due to potential secondary causes before diagnosis. ESID/PAGID criteria were met by 132 patients (males 52%), of whom, 106 had "probable" and 26 "possible CVID." Based on the population statistics in the three hospital districts, the minimum adult prevalence per 100,000 inhabitants in Finland for all CVID ("probable CVID," respectively) patients was 6.9 (5.5). In the highest prevalence district (Helsinki and Uusimaa), the prevalence was 7.7 (6.1). CVID patients suffer from frequent complications. Ten patients died during follow-up. Of probable CVID patients, 73% had more than one clinical phenotype. Intriguingly, gradual B cell loss from peripheral blood during follow-up was seen in as many as 16% of "Xprobable CVID" patients. Patients with possible CVID displayed somewhat milder clinical and laboratory phenotypes than probable CVID patients. We also confirm that large granular lymphocyte lymphoproliferation is a CVID-associated complication. Conclusion: The prevalence of CVID in Finland appears the highest recorded, likely reflecting the genetic isolation and potential founder effects in the Finnish population. Studies to discover potential gene variants responsible for the high prevalence in Finland thus seem warranted. Increased awareness of CVID among physicians would likely lead to earlier diagnosis and improved quality of care.Peer reviewe
Antipsychotic drug use in pregnancy: A multinational study from ten countries
Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across
four continents.
Methods: Individually linked health data in Denmark (2000−2012), Finland (2005–2014), Iceland (2004–2017),
Norway (2005–2015), Sweden (2006–2015), Germany (2006–2015), Australia (New South Wales, 2004–2012),
Hong Kong (2001–2015), UK (2006–2016), and the US (Medicaid, 2000–2013, and IBM MarketScan, 2012–2015)
were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of
pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy
until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated
with the use of antipsychotics.
Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas
atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over
time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries,
prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used
atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries.
Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by
varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early
pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population
Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006-2016: A study in the five Nordic countries, United States, and Australia
Purpose To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching.Methods We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with >= 1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester.Results Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%).Conclusions Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED
CHEK2 1100delC is prevalent in Swedish early onset familial breast cancer
<p>Abstract</p> <p>Background</p> <p>A truncating variant, 1100delC, in check point-kinase CHEK2, has been identified as a risk factor for familial and sporadic breast cancer. The prevalence in healthy non-breast cancer cases is low and varies between populations.</p> <p>Methods</p> <p>We analyzed the prevalence of <it>CHEK2 </it>1100delC in 763 breast cancer patients with a defined family history and 760 controls from the Stockholm region. The breast cancer patients originated from; a population-based cohort (n = 452) and from a familial cancer clinic (n = 311), the detailed family history was known in both groups.</p> <p>Results</p> <p>The variant was found in 2.9% of the familial cases from the population-based cohort and in 1.9% from the familial cancer clinic. In total 2.2% of the patients with a family history of breast cancer carried the variant compared to 0.7% of the controls (p = 0.03). There was no increased prevalence in sporadic patients (0.3%). The variant was most frequent in young familial patients (5.1% of cases ≤45 years, p = 0.003). The mean age at diagnosis of variant carriers was 12 years lower than in non-carriers (p = 0.001).</p> <p>Conclusion</p> <p>In conclusion, <it>CHEK2 </it>1100delC exists in the Swedish population. The prevalence is increased in familial breast cancer and the variant seems to influence age at onset.</p
Intranasal “painless” Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice
Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease (AD) treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V), which would allow increasing the dose of NGF without triggering pain. We show that “painless” hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8), hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of “painless” hNGF variants as a new generation of therapeutics for neurodegenerative diseases
N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells
IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models
Cancer Survival and Excess Mortality Estimates among Adolescents and Young Adults in Western Australia, 1982-2004: A Population-Based Study
Background: Data are limited on cancer outcomes in adolescents and young adults. Methods: Based on data from the Western Australian Data Linkage System, this study modelled survival and excess mortality in all adolescents and young adults aged 15-39 years in Western Australia who had a diagnosis of cancer in the period 1982-2004. Relative survival and excess all-cause mortality for all cancers combined and for principal tumour subgroups were estimated, using the Ederer II method and generalised linear Poisson modelling, respectively. Results: A cancer diagnosis in adolescents and young adults conferred substantial survival decrement. However, overall outcomes improved over calendar period (excess mortality hazard ratio [HR], latest versus earliest diagnostic period: 0.52, trend <0.0001). Case fatality varied according to age group (HR, oldest versus youngest: 1.38, trend <0.0001), sex (HR, female versus male: 0.66, 95% confidence interval [CI] 0.62-0.71), ethnicity (HR, Aboriginal versus others: 1.47, CI 1.23-1.76), geographical area (HR, rural/remote versus urban: 1.13, CI 1.04-1.23) and residential socioeconomic status (HR, lowest versus highest quartile: 1.14, trend <0.05). Tumour subgroups differed substantially in frequency according to age group and sex, and were critical outcome determinants. Conclusions: Marked progressive calendar-time improvement in overall outcomes was evident. Further research is required to disentangle the contributions of tumour biology and health service factors to outcome disparities between ethno-demographic, geographic and socioeconomic subgroups of adolescents and young adults with cancer. © 2013 Haggar et al
Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis
Despite high rates of exposure, only 5–10% of people
infected with Mycobacterium tuberculosis will develop active
tuberculosis (TB) disease, suggesting a significant role for genetic variation
in the human immune response to this infection. Here, we studied TB association
and expression of 18 genes involved in the Toll-like receptor (TLR) pathways.
Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients
and 387 controls from Indonesia. We found that four polymorphisms in the
TLR8 gene on chromosome X showed evidence of association
with TB susceptibility in males, including a non-synonymous polymorphism
rs3764880 (Met1Val; P = 0.007,
odds ratio (OR) = 1.8, 95%
c.i. = 1.2–2.7). We genotyped these
four TLR8 polymorphisms in an independent collection of 1,837
pulmonary TB patients and 1,779 controls from Russia and again found evidence of
association in males (for rs3764880
P = 0.03,
OR = 1.2, 95%
c.i. = 1.02–1.48). Combined evidence
for association is
P = 1.2×10−3–6×10−4.
In addition, a quantitative PCR analysis indicated that TLR8
transcript levels are significantly up-regulated in patients during the acute
phase of disease
(P = 9.36×10−5),
relative to baseline levels following successful chemotherapy. A marked increase
in TLR8 protein expression was also observed directly in differentiated
macrophages upon infection with M. bovis bacille
Calmette-Guérin (BCG). Taken together, our results provide evidence,
for the first time, of a role for the TLR8 gene in
susceptibility to pulmonary TB across different populations
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