93 research outputs found

    Pharmaco-epidemiology as a Tool in Pharmacovigilance: Studying cancer as adverse drug reaction

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    Pharmacovigilance is defined by the World Health Organization (WHO) as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problem. There has been concern about the safety of medicines since the discovery of congenital abnormalities in babies delivered by women who had taken thalidomide during pregnancy in 1961. An adverse drug reaction is defined as a response to a medicinal product which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration or modification of physiological function. Two types of adverse drug reactions are distinguished: type A reactions which are predictable from the known pharmacology of the medical substance and which are dose-dependent, and type B reactions which are idiosyncratic and unpredictable. It is clear that this is a very crude distinction which is, however, useful from the point of view of discovering unknown adverse reactions as early as possible. During drug development, the efficacy and safety of the active substance is investigated in clinical trials in a relatively small selected homogenous patient population, during a limited period of time. As around 80% of the adverse drug reactions is estimated to be of type A, a large number of the potential adverse drug reactions is documented during the clinical phase. After regulatory review and approval, during which all available information is reviewed, the marketing phase starts. Through marketing, the product is available for the entire population which is obviously far more heterogeneous than the study population. In contrast to the limited timeframe available during the clinical drug development phase, the post-marketing phase continues until the drug is withdrawn from the market. As a consequence, previously unknown adverse drug reactions might come to light, especially those of type B. Therefore, the obligation for the marketing authorization holder, as well as for regulatory authorities, for the continuous evaluation of safety and efficacy during the post marketing phase of a drug, have been legally laid down

    No association between blood-based markers of immune system and migraine status:a population-based cohort study

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    Background: Although some evidence implicates the immune system in migraine attacks, its role during attack-free periods remains largely unexplored. Therefore, we assessed the association between the immune system and migraine status. Methods: From the population-based Rotterdam Study, we included 6593 participants who underwent blood sampling and migraine assessments. In the blood samples, we measured white blood-cell-based immune markers. As a marker for the innate immune system, granulocyte and platelet counts were determined, whereas lymphocyte counts were used as a marker for the adaptive immune system. Migraine was assessed using a validated questionnaire based on ICHD-2 criteria. We investigated associations between blood-cell counts and migraine using logistic regression models adjusting for age, sex and other variables. Results: Mean age of participants was 65.6 ± 11.2 years and 56.7% were female. The lifetime prevalence of migraine was 15.1% (995/6593). We found no statistically significant associations between granulocyte (odds ratio [OR] per standard deviation increase 1.01 95% Confidence Interval [CI]: 0.93–1.09), platelet (OR 1.01 CI: 0.94–1.09) or lymphocyte counts (OR 1.01 CI: 0.93–1.08) and migraine status.Conclusions: Our results do not support an association between white blood-cell-based immunity markers and migraine status.</p

    No association between blood-based markers of immune system and migraine status:a population-based cohort study

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    Background: Although some evidence implicates the immune system in migraine attacks, its role during attack-free periods remains largely unexplored. Therefore, we assessed the association between the immune system and migraine status. Methods: From the population-based Rotterdam Study, we included 6593 participants who underwent blood sampling and migraine assessments. In the blood samples, we measured white blood-cell-based immune markers. As a marker for the innate immune system, granulocyte and platelet counts were determined, whereas lymphocyte counts were used as a marker for the adaptive immune system. Migraine was assessed using a validated questionnaire based on ICHD-2 criteria. We investigated associations between blood-cell counts and migraine using logistic regression models adjusting for age, sex and other variables. Results: Mean age of participants was 65.6 ± 11.2 years and 56.7% were female. The lifetime prevalence of migraine was 15.1% (995/6593). We found no statistically significant associations between granulocyte (odds ratio [OR] per standard deviation increase 1.01 95% Confidence Interval [CI]: 0.93–1.09), platelet (OR 1.01 CI: 0.94–1.09) or lymphocyte counts (OR 1.01 CI: 0.93–1.08) and migraine status.Conclusions: Our results do not support an association between white blood-cell-based immunity markers and migraine status.</p

    Under-representation of elderly in clinical trials: An analysis of the initial approval documents in the Food and Drug Administration database

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    Aims: To evaluate the availability of pharmacokinetic, safety and efficacy analyses specifically targeted at elderly, prior to the authorization of drugs. Methods: A cross‐sectional, structured review of publicly available initial approval documents of Food and Drug Administration‐approved drugs was performed. The 10 most frequently on‐label prescribed drug classes, drugs with known pharmacokinetic differences in the elderly or drugs that are relatively contraindicated in elderly (e.g. anticholinergics or benzodiazepines) were included in the analyses. Results: In total, 1129 unique active pharmaceutical ingredients were found eligible for the analyses, of

    Dysregulation of plasma circulating microRNAs in all-cause and cause-specific cancers:the Rotterdam Study

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    MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P &lt; 8.46 × 10− 5, 12 of them (miR-6124, miR-6778-5p, miR-5196, miR-654-5p, miR-4478, miR-4430, miR-4534, miR-1915-3p, miR-4644, miR-4292, miR-7111-5p, and miR-6870-5p) were also associated with prevalent hematologic tumors in the cross-sectional analysis at the baseline. In-silico analyses of the putative target genes of 13 identified miRNAs highlighted relevant genes and pathways linked to hematologic tumors. While no significant miRNA association was found for other four studied cancers, two miRNAs (miR-3157-5p and miR-3912-5p) showed nominal association with incident of three different cancer types. Overall, this study indicates that plasma levels of several miRNAs are dysregulated in hematologic tumors, highlighting their potential as biomarkers for early diagnosis as well as being involved in the pathogenesis of blood cancers.</p

    Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study

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    Novel prognostic inflammatory markers of cancer survival and cardiovascular disease are; the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-

    Isotretinoin exposure during pregnancy: A population-based study in the Netherlands

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    Objective: To estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.Design: Population-based study.Setting: The Netherlands.Participants: A cohort of 203 962

    Pathology-confirmed versus non pathology-confirmed cancer diagnoses: incidence, participant characteristics, and survival

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    Cancer diagnoses which are not confirmed by pathology are often under-registered in cancer registries compared to pathology-confirmed diagnoses. It is unknown how many patients have a non pathology-confirmed cancer diagnosis, and whether their characteristics and survival differ from patients with a pathology-confirmed diagnosis. Participants from the prospective population-based Rotterdam Study were followed between 1989 and 2013 for the diagnosis of cancer. Cancer diagnoses were classified into pathology-confirmed versus non pathology-confirmed (i.e., based on imaging or tumour markers). We compared participant characteristics and the distribution of cancers at different sites. Furthermore, we investigated differences in overall survival using survival curves adjusted for age and sex. During a median (interquartile range) follow-up of 10.7 (6.3–15.9) years, 2698 out of 14,024 participants were diagnosed with cancer, of which 316 diagnoses (11.7%) were non pathology-confirmed. Participants with non pathology-confirmed diagnoses were older, more often women, and had a lower education. Most frequently non pathology-confirmed cancer sites included central nervous system (66.7%), hepato-pancreato-biliary (44.5%), and unknown primary origin (31.2%). Survival of participants with non pathology-confirmed diagnoses after 1 year was lower compared to survival of participants with pathology-confirmed diagnoses (32.6% vs. 63.4%; risk difference of 30.8% [95% CI 25.2%; 36.2%]). Pathological confirmation of cancer is related to participant characteristics and cancer site. Furthermore, participants with non pathology-confirmed diagnoses have worse survival than participants with pathology-confirmed diagnoses. Missing data on non pathology-confirmed diagnoses may result in underestimation of cancer incidence and in an overestimation of survival in cancer registries, and may introduce bias in aetiological research

    Dietary mineral intake and lung cancer risk: the Rotterdam Study

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    Objective: Limited data are available on the role of mineral intake in the development of lung cancer (LC). We investigated whether dietary calcium, copper, iron, magnesium, selenium and zinc intake were associated with LC risk. Methods: We analyzed data from 5435 participants of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years and older. At baseline (1990–1993), diet was measured by a validated food frequency questionnaire. LC events were diagnosed on the basis of pathology data and medical records. Hazard ratios (HRs) on LC for energy-adjusted mineral intake were calculated using Cox regression models while adjusting for potential confounders. Results: During a follow-up period of 22 years, we identified 211 incident cases of LC. A higher zinc intake was associated with 42 % reduction in risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.35; 0.94, P-for trend = 0.039). Similarly, high intake of iron was associated with reduced risk of LC (top tertile vs. first tertile: HR 0.58, 95 % CI 0.37; 0.92, P-for trend = 0.02
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