Trends and risk factors of cutaneous melanoma in Europe

This thesis presents studies on different aspects of the epidemiology of melanoma: variations in disease frequency in time and place, determinants of melanoma incidence and variation in prognostic factor

Immunophenotyping of lymphocytes in healthy and immunodeficient children

This thesis describes the use of immunophenotyping of lymphocytes in healthy as well as immunodeficient children. Part I describes the applied techniques (Chapters 2 and 3). The experimental work in healthy children is described in Part II (Chapters 4-7) and Part III describes the experimental work in immunodeficient children (Chapters 8-13). A summary and discussion of the work is given in Part IV

Time trends in educational inequalities in cancer mortality in Colombia, 1998-2012

Objectives: To evaluate trends in premature cancer mortality in Colombia by educational level in three periods: 1998-2002 with low healthcare insurance coverage, 2003-2007 with rapidly increasing coverage and finally 2008-2012 with almost universal coverage (2008-2012). Setting: Colombian population-based, national secondary mortality data. Participants: We included all (n=188 091) cancer deaths occurring in the age group 20-64 years between 1998 and 2012, excluding only cases with low levels of quality of registration (n=2902, 1.5%). Primary and secondary outcome measures: In this descriptive study, we linked mortality data of ages 20-64 years to census data to obtain age-standardised cancer mortality rates by educational level. Using Poisson regression, we modelled premature mortality by educational level estimating rate ratios (RR), relative index of inequality (RII) and the Slope Index of Inequality (SII). Results: Relative measures showed increased risks of dying among the lower educated compared to the highest educated; this tendency was stronger in women (RRprimary1.49; RRsecondary1.22, both p<0.0001) than in men (RRprimary 1.35; RRsecondary 1.11, both p<0.0001). In absolute terms (SII), cancer caused a difference per 100 000 deaths between the highest and lowest educated of 20.5 in males and 28.5 in females. RII was significantly higher among women and the younger age categories. RII decreased between the first and second periods; afterwards (2008-2012), it increased significantly back to their previous levels. Among women, no significant increases or declines in cancer mortality over time were observed in recent periods in the lowest educated group, whereas strong recent declines were observed in those with secondary education or higher. Conclusions: Educational inequalities in cancer mortality in Colombia are increasing in absolute and relative terms, and are concentrated in young age categories. This trend was not curbed by increases in healthcare insurance coverage. Policymakers should focus on improving equal access to prevention, early detection, diagnostic and treatment facilities

The burden of cutaneous melanoma and status of preventive measures in Central and South America

Rationale and objective Very little is known about the burden of cutaneous melanoma in Central and South America, despite the existence of a reasonable amount of population-based data. We present data on melanoma incidence calculated in a standardized way for Central and South America, as well as an overview of primary and secondary prevention issues in the region. Methods Cancer registry data on all incident cases reported in the different registries present in Central and South America were combined to provide registry-based country estimates of age-standardized, sex-specific cutaneous melanoma incidence overall, and by histological subtype and anatomical site. A literature search provided additional information. Results Age-standardized incidence rates were between 1 and 5 per 100,000 and tended to be higher further away from the equator. Cutaneous melanomas of the acral type, mostly occurring on the lower limbs, are a distinguishing feature of melanoma in Central and South America in comparison with high-incidence areas. Several preventive measures, both primary and secondary, are in place, albeit largely without evaluation. Conclusion Due to incomplete registration and different registration practices, reliable and comparable data on melanoma were difficult to obtain; thus it is likely that the true burden of melanoma in Central and South America has been underestimated. The different characteristics of the cutaneous melanoma patient population in terms of anatomical site and histological type distribution imply a need for adapted primary and secondary prevention measures. The generally high ambient ultraviolet radiation levels require sufficient sun protection measures

Incidence, Prevalence and Future Trends of Primary Basal Cell Carcinoma in the Netherlands

Abstract: Basal cell carcinoma (BCC) incidence rates are increasing worldwide. This study’s objective was to estimate the occurrence of BCC in the Netherlands in terms of incidence and prevalence. Data on first primary carcinomas were retrieved from the Eindhoven Cancer Registry and extrapolated to the Dutch population. Extrapolated data showed a total of 444,131, histologically confirmed cases in the Netherlands between 1973 and 2008. During this period, age-adjusted incidence rates (European Standard Population) increased approximately three-fold from 40 to 148 per 100,000 in males and from 34 to 141 in females. Lifetime risk of BCC was 1 in 5–6 for Dutch citizens. Disease prevalence in the Netherlands was 1.4% and almost four times higher than this (5.4%) in the oldest age group (age 65 years or more). Predictions of future trends showed no signs of a plateau in the number of cases. These estimates should urge Dutch policymakers to provide solutions for the growing group of patients with BCC

Estimation of acute and chronic Q fever incidence in children during a three-year outbreak in the Netherlands and a comparison with international literature

Background:  In the Dutch 2007-2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. Methods:  As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0-15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007-2009. Results:  In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. Conclusion:  In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice

Quality of health care according to people with Down syndrome, their parents and support staff—A qualitative exploration

Background: People with Down syndrome (PDS) have complex healthcare needs. Little is known about the quality of health care for PDS, let alone how it is appraised by PDS and their caregivers. This study explores the perspectives of PDS, their parents and support staff regarding quality in health care for PDS. Method: The present authors conducted semi-structured interviews with 18 PDS and 15 parents, and focus groups with 35 support staff members (of PDS residing in assisted living facilities) in the Netherlands. Results: According to the participants, healthcare quality entails well-coordinated health care aligned with other support and care systems, a person-centred and holistic approach, including respect, trust and provider–patient communication adapted to the abilities of PDS. Conclusions: Our findings may be used to improve health care for PDS, and provide insight into how health care could match the specific needs of PDS

Migration from Mexico to the United States : a high-speedcancer transition

Q1Q1477-488Differences and similarities in cancer patterns between the country of Mexico and the United States' Mexican population, 11% of the entire US population, have not been studied. Mortality data from 2008 to 2012 in Mexico and California were analyzed and compared for causes of cancer death among adult and pediatric populations, using standard techniques and negative binomial regression. A total of 380,227 cancer deaths from Mexico and California were included. Mexican Americans had 49% and 13% higher mortality than their counterparts in Mexico among males and females, respectively. For Mexican Immigrants in the US, overall cancer mortality was similar to Mexico, their country of birth, but all‐cancers‐combined rates mask wide variation by specific cancer site. The most extreme results were recorded when comparing Mexican Americans to Mexicans in Mexico: with mortality rate ratios ranging from 2.72 (95% CI: 2.44–3.03) for colorectal cancer in males to 0.28 (95% CI: 0.24–0.33) for cervical cancer in females. These findings further reinforce the preeminent role that the environment, in its multiple aspects, has on cancer. Overall, mortality from obesity and tobacco‐related cancers was higher among Mexican origin populations in the US compared to Mexico, suggesting a higher risk for these cancers, while mortality from prostate, stomach, and especially cervical and pediatric cancers was markedly higher in Mexico. Among children, brain cancer and neuroblastoma patterns suggest an environmental role in the etiology of these malignancies as well. Partnered research between the US and Mexico for cancer studies is warranted

Dissemination of Direct Healthcare Professional Communications on Medication Errors for Medicinal Products in the EU:An Explorative Study on Relevant Factors

Introduction When serious medication errors (ME) are identified, communication to the field may be necessary. In the EU, communication of serious safety issues, such as medication errors associated with adverse drug reactions, is done through direct healthcare professional communications (DHPCs). We aimed to identify how often DHPCs about medication errors are distributed, and we explored factors associated with these ME DHPCs. Methods We performed a descriptive study of all centrally authorised products (CAPs) approved before 1 May 2019 in the EU. All DHPCs issued between 1 January 2001 and 1 May 2019 were reviewed for ME content. Characteristics of CAPs were collected from the website of the European Medicines Agency. A Kaplan-Meier survival analysis was performed to estimate the 5- and 10-year probability of the occurrence of a first ME DHPC. A logistic regression was performed to explore risk factors for ME DHPCs. Results A total of 678 CAPs were included, of which 35 required an ME DHPC during the study period. The 5-year probability for a CAP to have a first ME DHPC was 2.5% (95% CI 1.1-3.9) and the 10-year probability was 4.4% (95% CI 2.2-6.5). Among products with an ME DHPC, the 5-year probability of a second ME DHPC was 21.3% (95% CI 0.2-38.0). The risk of ME DHPCs was increased for products with multiple pharmaceutical formulations, enteral liquid or parenteral injection preparations, and products classified as nervous system agents or antineoplastic and immunomodulating agents. Conclusions The absolute number of ME DHPCs for CAPs is low and does not give rise to immediate concern. We identified potential risk factors for ME DHPCs that should be taken into account during approval procedures or line extensions