Publications by authors named "Esther de Vries"

176 Publications

Palliative Care and Oncology in Colombia: The Potential of Integrated Care Delivery.

Healthcare (Basel) 2021 Jun 23;9(7). Epub 2021 Jun 23.

Department of Clinical Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Palliative care is on the global health agenda, as only approximately 14% of people who require palliative care receive it [...].
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http://dx.doi.org/10.3390/healthcare9070789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304350PMC
June 2021

Which triggers could support timely identification of primary antibody deficiency? A qualitative study using the patient perspective.

Orphanet J Rare Dis 2021 Jun 29;16(1):289. Epub 2021 Jun 29.

Department of Tranzo, TSB, Tilburg University, PO Box 90153, 5000 LE, Tilburg, The Netherlands.

Background: Patients with predominantly (primary) antibody deficiencies (PADs) commonly develop recurrent respiratory infections which can lead to bronchiectasis, long-term morbidity and increased mortality. Recognizing symptoms and making a diagnosis is vital to enable timely treatment. Studies on disease presentation have mainly been conducted using medical files rather than direct contact with PAD patients. Our study aims to analyze how patients appraised their symptoms and which factors were involved in a decision to seek medical care.

Methods: 14 PAD-patients (11 women; median 44, range 16-68 years) were analyzed using semi-structured interviews until saturation of key emergent themes was achieved.

Results: Being always ill featured in all participant stories. Often from childhood onwards periods of illness were felt to be too numerous, too bad, too long-lasting, or antibiotics were always needed to get better. Recurrent or persistent respiratory infections were the main triggers for patients to seek care. All participants developed an extreme fatigue, described as a feeling of physical and mental exhaustion and thus an extreme burden on daily life that was not solved by taking rest. Despite this, participants tended to normalize their symptoms and carry on with usual activities. Non-immunologists, as well as patients, misattributed the presenting signs and symptoms to common, self-limiting illnesses or other 'innocent' explanations. Participants in a way understood the long diagnostic delay. They know that the disease is rare and that doctors have to cover a broad medical area. But they were more critical about the way the doctors communicate with them. They feel that doctors often don't listen very well to their patients. The participants' symptoms as well as the interpretation of these symptoms by their social environment and doctors had a major emotional impact on the participants and a negative influence on their future perspectives.

Conclusions: To timely identify PAD, 'pattern recognition' should not only focus on the medical 'red flags', but also on less differentiating symptoms, such as 'being always ill' and 'worn out' and the way patients cope with these problems. And, most important, making time to really listen to the patient remains the key.
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http://dx.doi.org/10.1186/s13023-021-01918-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243743PMC
June 2021

Test, trace, isolate: evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort.

Diagn Microbiol Infect Dis 2021 Apr 21;101(2):115392. Epub 2021 Apr 21.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Electronic address:

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% - 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on 'test, trace and isolate'. Keywords: SARS-CoV-2, RT-PCR, serology, sensitivity, public health.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059257PMC
April 2021

Predicting emergency department visits in a large teaching hospital.

Int J Emerg Med 2021 Jun 12;14(1):34. Epub 2021 Jun 12.

Jeroen Bosch Academy Research, Jeroen Bosch Hospital, PO Box 90153, 5200ME, 's-Hertogenbosch, the Netherlands.

Background: Emergency department (ED) visits show a high volatility over time. Therefore, EDs are likely to be crowded at peak-volume moments. ED crowding is a widely reported problem with negative consequences for patients as well as staff. Previous studies on the predictive value of weather variables on ED visits show conflicting results. Also, no such studies were performed in the Netherlands. Therefore, we evaluated prediction models for the number of ED visits in our large the Netherlands teaching hospital based on calendar and weather variables as potential predictors.

Methods: Data on all ED visits from June 2016 until December 31, 2019, were extracted. The 2016-2018 data were used as training set, the 2019 data as test set. Weather data were extracted from three publicly available datasets from the Royal Netherlands Meteorological Institute. Weather observations in proximity of the hospital were used to predict the weather in the hospital's catchment area by applying the inverse distance weighting interpolation method. The predictability of daily ED visits was examined by creating linear prediction models using stepwise selection; the mean absolute percentage error (MAPE) was used as measurement of fit.

Results: The number of daily ED visits shows a positive time trend and a large impact of calendar events (higher on Mondays and Fridays, lower on Saturdays and Sundays, higher at special times such as carnival, lower in holidays falling on Monday through Saturday, and summer vacation). The weather itself was a better predictor than weather volatility, but only showed a small effect; the calendar-only prediction model had very similar coefficients to the calendar+weather model for the days of the week, time trend, and special time periods (both MAPE's were 8.7%).

Conclusions: Because of this similar performance, and the inaccuracy caused by weather forecasts, we decided the calendar-only model would be most useful in our hospital; it can probably be transferred for use in EDs of the same size and in a similar region. However, the variability in ED visits is considerable. Therefore, one should always anticipate potential unforeseen spikes and dips in ED visits that are not shown by the model.
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http://dx.doi.org/10.1186/s12245-021-00357-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196936PMC
June 2021

Decision making in the end-of-life care of patients who are terminally ill with cancer - a qualitative descriptive study with a phenomenological approach from the experience of healthcare workers.

BMC Palliat Care 2021 May 28;20(1):76. Epub 2021 May 28.

Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Pontificia Universidad Javeriana, Bogota, Colombia.

Background: In Colombia, recent legislation regarding end-of-life decisions includes palliative sedation, advance directives and euthanasia. We analysed which aspects influence health professionals´ decisions regarding end-of-life medical decisions and care for cancer patients.

Methods: Qualitative descriptive-exploratory study based on phenomenology using semi-structured interviews. We interviewed 28 oncologists, palliative care specialists, general practitioners and nurses from three major Colombian institutions, all involved in end-of-life care of cancer patients: Hospital Universitario San Ignacio and Instituto Nacional de Cancerología in Bogotá and Hospital Universitario San José in Popayan.

Results: When making decisions regarding end-of-life care, professionals consider: 1. Patient's clinical condition, cultural and social context, in particular treating indigenous patients requires special skills. 2. Professional skills and expertise: training in palliative care and experience in discussing end-of-life options and fear of legal consequences. Physicians indicate that many patients deny their imminent death which hampers shared decision-making and conversations. They mention frequent ambiguity regarding who initiates conversations regarding end-of-life decisions with patients and who finally takes decisions. Patients rarely initiate such conversations and the professionals normally do not ask patients directly for their preferences. Fear of confrontation with family members and lawsuits leads healthcare workers to carry out interventions such as initiating artificial feeding techniques and cardiopulmonary resuscitation, even in the absence of expected benefits. The opinions regarding the acceptability of palliative sedation, euthanasia and use of medications to accelerate death without the patients´ explicit request vary greatly. 3. Conditions of the insurance system: limitations exist in the offer of oncology and palliative care services for important proportions of the Colombian population. Colombians have access to opioid medications, barriers to their application are largely in delivery by the health system, the requirement of trained personnel for intravenous administration and ambulatory and home care plans which in Colombia are rare.

Conclusions: To improve end-of-life decision making, Colombian healthcare workers and patients need to openly discuss wishes, needs and care options and prepare caregivers. Promotion of palliative care education and development of palliative care centres and home care plans is necessary to facilitate access to end-of-life care. Patients and caregivers' perspectives are needed to complement physicians' perceptions and practices.
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http://dx.doi.org/10.1186/s12904-021-00768-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164310PMC
May 2021

Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity.

J Allergy Clin Immunol 2021 May 12. Epub 2021 May 12.

Department of Immunology, Great Ormond Street (GOS) Hospital for Children NHS Foundation Trust, London, United Kingdom.

Background: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms.

Objectives: We sought to systematically review available terms in HPO for the depiction of IEIs, to expand HPO, yielding more comprehensive sets of terms, and to reannotate IEIs with HPO terms to provide accurate, standardized phenotypic descriptions.

Methods: We initiated a collaboration involving expert clinicians, geneticists, researchers working on IEIs, and bioinformaticians. Multiple branches of the HPO tree were restructured and extended on the basis of expert review. Our ontology-guided machine learning coupled with a 2-tier expert review was applied to reannotate defined subgroups of IEIs.

Results: We revised and expanded 4 main branches of the HPO tree. Here, we reannotated 73 diseases from 4 International Union of Immunological Societies-defined IEI disease subgroups with HPO terms. We achieved a 4.7-fold increase in the number of phenotypic terms per disease. Given the new HPO annotations, we demonstrated improved ability to computationally match selected IEI cases to their known diagnosis, and improved phenotype-driven disease classification.

Conclusions: Our targeted expansion and reannotation presents enhanced precision of disease annotation, will enable superior HPO-based IEI characterization, and hence benefit both IEI diagnostic and research activities.
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http://dx.doi.org/10.1016/j.jaci.2021.04.033DOI Listing
May 2021

The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency.

Clin Exp Immunol 2021 Aug 1;205(2):213-221. Epub 2021 Jun 1.

Department of Tranzo, Tilburg University, Tilburg, the Netherlands.

Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in 's-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as 'no PAD'. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63-0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62-0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51-0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85-1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential 'specific IgA or IgM antibody deficiency' in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.
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http://dx.doi.org/10.1111/cei.13605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274160PMC
August 2021

Lessons Learned From the Clinical Presentation of Common Variable Immunodeficiency Disorders: A Systematic Review and Meta-Analysis.

Front Immunol 2021 23;12:620709. Epub 2021 Mar 23.

Department of Tranzo, Tilburg University, Tilburg, Netherlands.

Background: Diagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection.

Objective: To systematically review all existing data on the clinical presentation of CVID.

Methods: PubMed, EMBASE and Cochrane were searched for cohort studies, published January/1999-December/2019, detailing the clinical manifestations before, at and after the CVID-diagnosis.

Results: In 51 studies (n=8521 patients) 134 presenting and 270 total clinical manifestations were identified. Recurrent upper and/or lower respiratory infections were present at diagnosis in 75%. Many patients had suffered severe bacterial infections (osteomyelitis 4%, meningitis 6%, septicemia 8%, mastoiditis 8%). Bronchiectasis (28%), lymphadenopathy (27%), splenomegaly (13%), inflammatory bowel disease (11%), autoimmune cytopenia (10%) and idiopathic thrombocytopenia (6%) were also frequently reported. A bimodal sex distribution was found, with male predominance in children (62%) and female predominance in adults (58%). 25% of CVID-patients developed other manifestations besides infections in childhood, this percentage was much higher in adults (62%). Immune-dysregulation features, such as granulomatous-lymphocytic interstitial lung disease and inflammatory bowel disease, were more prominent in adults.

Conclusions: The shift from male predominance in childhood to female predominance in adults suggests differences in genetic and environmental etiology in CVID and has consequences for pathophysiologic studies. We confirm the high frequency of respiratory infections at presentation, but also show a high incidence of severe bacterial infections such as sepsis and meningitis, and immune dysregulation features including lymphoproliferative, gastrointestinal and autoimmune manifestations. Early detection of CVID may be improved by screening for antibody deficiency in patients with these manifestations.
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http://dx.doi.org/10.3389/fimmu.2021.620709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021796PMC
June 2021

What do patients and dermatologists prefer regarding low-risk basal cell carcinoma follow-up care? A discrete choice experiment.

PLoS One 2021 29;16(3):e0249298. Epub 2021 Mar 29.

Section of Health Technology Assessment & Erasmus Choice Modelling Centre, Erasmus School of Health Policy & Management, Erasmus University, Rotterdam, The Netherlands.

Background: Follow-up after low-risk basal cell carcinoma (BCC) is being provided more frequently than recommended by guidelines. To design an acceptable strategy to successfully reduce this 'low-value' care, it is important to obtain insights into the preferences of patients and dermatologists.

Objective: To determine the preferences and needs of patients and dermatologists to reduce low-risk BCC follow-up care, and the trade-offs they are willing to make.

Methods: A questionnaire including a discrete choice experiment was created, containing attributes regarding amount of follow-up, continuity of care, method of providing addition information, type of healthcare provider, duration of follow-up visits and skin examination. In total, 371 BCC patients and all Dutch dermatologists and dermatology residents (n = 620) were invited to complete the questionnaire. A panel latent class model was used for analysis.

Results: Eighty-four dermatologists and 266 BCC patients (21% and 72% response rates respectively) completed the discrete choice experiment. If the post-treatment visit was performed by the same person as treatment provider and a hand-out was provided to patients containing personalised information, the acceptance of having no additional follow-up visits (i.e. following the guidelines) would increase from 55% to 77% by patients. Female patients and older dermatologists, however, are less willing to accept the guidelines and prefer additional follow-up visits.

Limitations: The low response rate of dermatologists.

Conclusion: This discrete choice experiment revealed a feasible strategy to substantially reduce costs, while maintaining quality of care, based on the preferences and needs of BCC patients, which is supported by dermatologists.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249298PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007023PMC
March 2021

Immunoglobulin Replacement Therapy is critical and cost-effective in increasing life expectancy and quality of life in patients suffering from Common Variable Immunodeficiency Disorders (CVID): A health-economic assessment.

PLoS One 2021 4;16(3):e0247941. Epub 2021 Mar 4.

Dept Tranzo, Tilburg School of Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands.

Background: Common variable immunodeficiency disorders (CVID), the most common form of primary antibody deficiency, are rare conditions associated with considerable morbidity and mortality. The clinical benefit of immunoglobulin replacement therapy (IgGRT) is substantial: timely treatment with appropriate doses significantly reduces mortality and the incidence of CVID-complications such as major infections and bronchiectasis. Unfortunately, CVID-patients still face a median diagnostic delay of 4 years. Their disease burden, expressed in annual loss of disability-adjusted life years, is 3-fold higher than in the general population. Hurdles to treatment access and reimbursement by healthcare payers may exist because the value of IgGRT is poorly documented. This paper aims to demonstrate cost-effectiveness and cost-utility (on life expectancy and quality) of IgGRT in CVID.

Methods And Findings: With input from a literature search, we built a health-economic model for cost-effectiveness and cost-utility assessment of IgGRT in CVID. We compared a mean literature-based dose (≥450mg/kg/4wks) to a zero-or-low dose (0 to ≤100 mg/kg/4wks) in a simulated cohort of adult patients from time of diagnosis until death; we also estimated the economic impact of diagnostic delay in this simulated cohort. Compared to no or minimal treatment, IgGRT showed an incremental benefit of 17 life-years (LYs) and 11 quality-adjusted life-years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €29,296/LY and €46,717/QALY. These results were robust in a sensitivity analysis. Reducing diagnostic delay by 4 years provided an incremental benefit of six LYs and four QALYs compared to simulated patients with delayed IgGRT initiation, resulting in an ICER of €30,374/LY and €47,495/QALY.

Conclusions: The health-economic model suggests that early initiation of IgGRT compared to no or delayed IgGRT is highly cost-effective. CVID-patients' access to IgGRT should be facilitated, not only because of proven clinical efficacy, but also due to the now demonstrated cost-effectiveness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247941PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932530PMC
March 2021

Breast cancer in Colombia: a growing challenge for the healthcare system.

Breast Cancer Res Treat 2021 Feb 21;186(1):15-24. Epub 2021 Feb 21.

Global Cancer Institute, Boston, MA, USA.

Aim: To provide a comprehensive overview of breast cancer in Colombia.

Methods: Data on breast cancer in Colombia are scarce. We present incidence data from population-based cancer registries that represent 4 distinct regions of the country. Other data originate from non-governmental institutions and healthcare providers within Colombia, official sources, expert opinion, Colombian legislation, and the Cancer Mortality Atlas publishes by Colombian National Cancer Institute.

Results: In Colombia, the age-standardized incidence rate remained relatively stable between 2012 and 2020 (43.1 to 47.8 cases per 100,000 women-years); Additionally, survival since 1995 has presented a substantial improvement from 65.7 to 72.1. In 33% of cases, the diagnosis of breast cancer was made in advanced stages, stage III or higher. The health demography survey conducted in 2015 showed that the participation in mammography screening in women aged 40 to 69 remains low 48.1%. Some limitations regarding access to early detection and diagnosis include economic strata, health insurance coverage, origin, and accessibility. On average, a 90-day period was reported from onset of symptoms to diagnosis of breast cancer.

Conclusion: The first action towards improving outcomes in breast cancer should be to improve stage at diagnosis and timely access to care.
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http://dx.doi.org/10.1007/s10549-020-06091-6DOI Listing
February 2021

Respiratory Symptoms in Post-infancy Children. A Dutch Pediatric Cohort Study.

Front Pediatr 2020 17;8:583630. Epub 2020 Dec 17.

Centre for Language Studies, Radboud University, Nijmegen, Netherlands.

To study the pattern of respiratory symptoms in children in the general population. We followed a cohort of children for up to 2 years through parents completing weekly online questionnaires in the Child-Is-Ill study ("Kind-en-Ziekmeting" in Dutch); the study was running 2012-2015. Inclusion criteria were "an ordinary child" (according to the parents) and <18 years old at inclusion. We especially encouraged participation of post-infancy children. Age at inclusion, sex, smoking exposure, allergy in the family, and frequent infections in the family were noted. Pearson's correlation, principal component analysis, latent class analysis, latent profile analysis, linear regression, and linear mixed effects regression were used in the statistical analyses. Data were collected on 55,524 childweeks in 755 children (50% girls; median age, 7 years; interquartile range, 4-11 years, 97% ≥2 years at inclusion), with reported symptom(s) in 8,425 childweeks (15%), leading to school absenteeism in 25%, doctor's visits in 12%, and parental sick leave in 8%; symptoms lasting ≥3 weeks were rare (2% of episodes). Linear mixed effects regression showed significant, but only limited, effects of season on the proportion of "symptom(s) reported" per individual child. Only runny nose showed a significant, but very small, age effect. However, the variability between the children was considerable. There were no obvious subgroups of children with specific symptom combinations. In any randomly chosen week, the vast majority of children (85%) in our-mainly-post-infancy cohort derived from the general population did not have any symptom, even in the younger age group, even in winter. The children showed considerable variability; no clear subgroups of symptom patterns could be identified, underlining the difficult position of healthcare providers. These results support our opinion that post-infancy children in the general population should not be evaluated as if they are infants when they have recurrent respiratory symptoms. If they clearly deviate from the above-described most common pattern, it is wise to keep an eye on potential, maybe even rare, serious underlying causes.
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http://dx.doi.org/10.3389/fped.2020.583630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773946PMC
December 2020

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

Drug Saf 2021 Jan;44(1):73-82

Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1007/s40264-020-00995-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813691PMC
January 2021

Progress, challenges and ways forward supporting cancer surveillance in Latin America.

Int J Cancer 2021 Jul 14;149(1):12-20. Epub 2020 Dec 14.

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Population-based cancer registries (PBCRs) are the only means to provide reliable incidence and survival data as a basis for policy-making and resource allocations within cancer care. Yet, less than 3% and 10% of the respective populations of Central America and South America are covered by high-quality cancer registries. The Global Initiative for Cancer Registry Development provides support to improve this situation via the International Agency for Research on Cancer Regional Hub for Latin America. In this paper, we summarize activities (advocacy, technical assistance, training and research) over the last 5 years, their impact and current challenges, including the implementation of new PBCR in four countries in the region. Despite the favorable political support to cancer registration in many countries, the sustainability of cancer registration remains vulnerable. Renewed efforts are needed to improve data quality in Latin America while ensuring maximum visibility of the data collected by disseminating and promoting their use in cancer control.
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http://dx.doi.org/10.1002/ijc.33407DOI Listing
July 2021

Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency.

J Clin Immunol 2021 Feb 18;41(2):382-392. Epub 2020 Nov 18.

Department of Pediatric Immunology and Infectious Diseases, UMC Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands.

Background: Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study.

Objective: To compare the efficacy of PA and IRT in a randomized crossover trial.

Methods: A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared.

Results: The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01).

Conclusion: We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT.

Clinical Implication: Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.
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http://dx.doi.org/10.1007/s10875-020-00841-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858555PMC
February 2021

Providing person-centered care for patients with complex healthcare needs: A qualitative study.

PLoS One 2020 16;15(11):e0242418. Epub 2020 Nov 16.

Department of Tranzo, Tilburg School of Social and Behavioral Sciences, Tilburg University, Tilburg, Noord-Brabant, The Netherlands.

Background: People with chronic conditions have complex healthcare needs that lead to challenges for adequate healthcare provision. Current healthcare services do not always respond adequately to their needs. A modular perspective, in particular providing visualization of the modular service architecture, is promising for improving the responsiveness of healthcare services to the complex healthcare needs of people with chronic conditions. The modular service architecture provides a comprehensive representation of the components and modules of healthcare provision. In this study, we explore this further in a qualitative multiple case study on healthcare provision for children with Down syndrome in the Netherlands.

Methods: Data collection for four cases involved 53 semi-structured interviews with healthcare professionals and 21 semi-structured interviews with patients (the parents of children with Down syndrome as proxy). In addition, we gathered data by means of practice observations and analysis of relevant documents. The interviews were audio-recorded, transcribed verbatim and analyzed utilizing the Miles and Huberman approach.

Results: Our study shows that the perspectives on healthcare provision of professionals and patients differ substantially. The visualization of the modular service architecture that was based on the healthcare professionals' perspective provided a complete representation of (para)medical outcomes relevant to the professionals' own discipline. In contrast, the modular service architecture based on the patients' perspective, which we define as a person-centered modular service architecture, provided a representation of the healthcare service that was primarily based on functional outcomes and the overall wellbeing of the patients.

Conclusion: Our study shows that visualization of the modular service architecture can be a useful tool to better address the complex needs and requirements of people with a chronic condition. We suggest that a person-centered modular service architecture that focuses on functional outcomes and overall wellbeing, enables increased responsiveness of healthcare services to people with complex healthcare needs and provision of truly person-centered care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668580PMC
January 2021

Childhood cancer in Latin America: from detection to palliative care and survivorship.

Cancer Epidemiol 2021 04 26;71(Pt B):101837. Epub 2020 Oct 26.

Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Pontificia Universidad Javeriana, Carrera 7 No. 40 - 62 Bogota, Colombia. Electronic address:

Background: Treatment options for childhood cancer have improved substantially, although in many low- and middle-income countries survival is lagging behind. Integral childhood cancer care involves the whole spectrum from detection and diagnosis to palliative and survivorship care.

Methods: Based on a literature review and expert opinions, we summarized current practice and recommendations on the following aspects of childhood cancer in Latin America: diagnostic processes and time to diagnosis, stage at diagnosis, treatments and complications, survivorship programs and palliative care and end-of-life services.

Results: Latin America is a huge and heterogeneous continent. Identified barriers show similar problems between countries, both logistically (time and distance to centers, treatment interruptions) and financially (cost of care, cost of absence from work). Governmental actions in several countries improved the survival of children with cancer, but difficulties persist in timely diagnosis and providing adequate treatment to all childhood cancer patients in institutions with complete infrastructure. Treatment abandonment is still common, although the situation is improving. Cancer care in the region has mostly focused on acute treatment of the disease and has not adequately considered palliative and end-of-life care and monitoring of survivors.

Conclusions: Decentralizing diagnostic activities and centralizing specialized treatment will remain necessary; measures to facilitate logistics and costs of transportation of the child and caretakers should be implemented. Twinning actions with specialized centers in high income countries for help in diagnosis, treatment and education of professionals and family members have been shown to work. Palliative and end-of-life care as well as childhood cancer survivorship plans are needed.
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http://dx.doi.org/10.1016/j.canep.2020.101837DOI Listing
April 2021

Theoretical reduction of the incidence of colorectal cancer in Colombia from reduction in the population exposure to tobacco, alcohol, excess weight and sedentary lifestyle: a modelling study.

BMJ Open 2020 10 28;10(10):e037388. Epub 2020 Oct 28.

School of Nutrition and Dietetics, Industrial University of Santander, Bucaramanga, Colombia.

Aims: To determine the potential impact fraction of alcohol and tobacco consumption, high body mass index and low physical activity on colorectal cancer burden in Colombia for the period 2016-2050.

Methods: Based on age-specific and sex-specific data on colorectal cancer incidence, data from population-based surveys for the exposure data and population projections, the macrosimulation model Prevent V.3.01 was used to model expected colorectal cancer incidence for the period 2016-2050. Baseline models were those where exposure levels were not subject to change because of interventions. Two intervention scenarios were specified: one with elimination of exposure to the risk factor as of 2017 and a second one where over a 10-year period the current prevalence data gradually declined until they reach 90% of the 2016 levels.

Results: Under the reference scenarios, a total number of 274 637 colorectal cancers would be expected to occur in the period 2016-2050. Under the scenario of 10% gradual decline in the prevalence of alcohol and tobacco consumption, physical inactivity and high body mass index, a total of 618, 488, 2954 and 2086 new cases, respectively, would be avoided. Under scenarios of elimination, these numbers of avoided cases would be 6908 (elimination alcohol), 6104 (elimination tobacco), 16 637 (optimizing physical inactivity) and 25 089 (all on ideal weight).

Conclusions: In order to reduce the burden of colorectal cancer, it is important to take measures to halt the current trends of increasing sedentary behaviour and overweight in the Colombian population. Proportionally, alcohol and tobacco consumption are less important population risk factors for colorectal cancer.
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http://dx.doi.org/10.1136/bmjopen-2020-037388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594367PMC
October 2020

C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

Clin Infect Dis 2021 07;73(2):e383-e390

Department of Paediatrics, Division of Paediatric Infectious Diseases & Immunology, Erasmus Medical Centre, University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.

Background: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful.

Methods: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis).

Results: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis.

Conclusions: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
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http://dx.doi.org/10.1093/cid/ciaa876DOI Listing
July 2021

Risk factors for atopic diseases and recurrent respiratory tract infections in children.

Pediatr Pulmonol 2020 11 15;55(11):3168-3179. Epub 2020 Sep 15.

Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

Introduction: The simultaneously increased prevalence of atopic diseases and decreased prevalence of infectious diseases might point to a link between the two entities. Past work mainly focused on either atopic diseases or recurrent infections. We aim to investigate whether risk factors for atopic diseases (ie, asthma, allergic rhinitis, atopic dermatitis, and/or food allergy) differ from risk factors for recurrent respiratory tract infections (RRTIs) in children.

Methods: Cross-sectional data were used from 5517 children aged 1 to 18 years who participated in an Electronic Portal for children between 2011 and 2019. Univariable/multivariable logistic regression analyses were performed to determine risk factors for any atopic disease and RRTIs.

Results: Children aged ≥5 years were more likely to have any atopic disease (adjusted odds ratio [OR]: 1.50-2.77) and less likely to have RRTIs (OR: 0.68-0.84) compared to children aged less than 5 years. Female sex (OR: 0.72; 95% confidence interval [CI]: 0.63-0.81), low birth weight (OR: 0.74; 95% CI: 0.57-0.97) and dog ownership (OR: 0.79; 95% CI: 0.66-0.95) reduced the odds of any atopic disease, but not of RRTIs. Daycare attendance (OR: 1.22; 95% CI: 1.02-1.47) was associated with RRTIs, but not with atopic diseases. A family history of asthma, allergic rhinitis, atopic dermatitis, and RRTIs was significantly associated with the same entity in children, with OR varying from 1.58 (95% CI: 1.35-1.85) in allergic rhinitis to 2.20 (95% CI: 1.85-2.61) in asthma.

Conclusion: Risk factors for atopic diseases are distinct from risk factors for RRTIs, suggesting that the changing prevalence of both entities is not related to shared risk factors.
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http://dx.doi.org/10.1002/ppul.25042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589449PMC
November 2020

Capturing the complexity of healthcare for people with Down syndrome in quality indicators - a Delphi study involving healthcare professionals and patient organisations.

BMC Health Serv Res 2020 Jul 27;20(1):694. Epub 2020 Jul 27.

Tranzo, Scientific Center for Care and Wellbeing, Faculty of Social and Behavioral Sciences, Tilburg University, PO Box 90153, 5000, LE, Tilburg, The Netherlands.

Background: Insight into quality of healthcare for people with Down Syndrome (DS) is limited. Quality indicators (QIs) can provide this insight. This study aims to find consensus among participants regarding QIs for healthcare for people with DS.

Methods: We conducted a four-round Delphi study, in which 33 healthcare professionals involved in healthcare for people with DS and two patient organisations' representatives in the Netherlands participated. Median and 75-percentiles were used to determine consensus among the answers on 5-point Likert-scales. In each round, participants received an overview of participants' answers from the previous round.

Results: Participants agreed (consensus was achieved) that a QI-set should provide insight into available healthcare, enable healthcare improvements, and cover a large diversity of quality domains and healthcare disciplines. However, the number of QIs in the set should be limited in order to prevent registration burden. Participants were concerned that QIs would make quality information about individual healthcare professionals publicly available, which would induce judgement of healthcare professionals and harm quality, instead of improving it.

Conclusions: We unravelled the complexity of capturing healthcare for people with DS in a QI-set. Patients' rights to relevant information have to be carefully balanced against providers' entitlement to a safe environment in which they can learn and improve. A QI-set should be tailored to different healthcare disciplines and information systems, and measurement instruments should be suitable for collecting information from people with DS. Results from this study and two preceding studies, will form the basis for the further development of a QI-set.
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http://dx.doi.org/10.1186/s12913-020-05492-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385945PMC
July 2020

Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.

J Allergy Clin Immunol 2020 10 9;146(4):901-911. Epub 2020 Apr 9.

Primary Immunodeficiencies Unit, Hospital Dona Estefania, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes.

Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations.

Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling.

Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents.

Conclusions: We present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.
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http://dx.doi.org/10.1016/j.jaci.2019.11.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246418PMC
October 2020

Overdiagnosis of cow's milk allergy with home reintroduction.

Pediatr Allergy Immunol 2020 08 28;31(6):704-706. Epub 2020 Apr 28.

UMCG, Beatrix Children's Hospital, Paediatric Pulmonology & Allergology, University of Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1111/pai.13251DOI Listing
August 2020

Drug Safety Issues Covered by Lay Media: A Cohort Study of Direct Healthcare Provider Communications Sent between 2001 and 2015 in The Netherlands.

Drug Saf 2020 07;43(7):677-690

Department of Clinical Pharmacy and Pharmacology (EB70), University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Background: Some drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not.

Objectives: The objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage.

Methods: Newspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage.

Results: 41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64-10.73)]. Negative associations were seen for time since market approval [3-5 years 0.30; (0.11-0.82), 6-11 years 0.18; (0.06-0.58)] and year of the DHPC [0.88; (0.81-0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56-30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03-14.66)].

Conclusions: Newspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication.
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http://dx.doi.org/10.1007/s40264-020-00922-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305079PMC
July 2020

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

J Appl Res Intellect Disabil 2020 May 13;33(3):496-514. Epub 2019 Dec 13.

Tranzo, Scientific Center for Care and Wellbeing, Faculty of Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands.

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.
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http://dx.doi.org/10.1111/jar.12692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187228PMC
May 2020

Access to diagnostic facilities in children with cancer in Colombia: Spotting opportunity and distance from a sample.

Cancer Epidemiol 2020 02 28;64:101645. Epub 2019 Nov 28.

Department of Clinical Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogotá, Colombia.

Objectives: Delivering health care timely and geographically accessible are determining factors for the prognosis of children with cancer. This study analyzed geographic access and timeliness to diagnostic services in Colombia.

Methods: In this Colombian national childhood cancer database-based study, patients and their diagnostic facilities were individually and separately space positioned. Distances between the household to the diagnostic facility, and between the clinical date of suspicion and diagnosis were determined. Using exploratory data analysis, we obtained a probability density function (lambda), which expressed a correlation percentage between the residential location of the patient and either travel time or timeliness of treatment.

Results: 27 % of the sample of 731 patients had access to diagnostic centres in less than 30 min. The travel-distance to diagnostic centres was lowest in the Caribe and Andina Regions (43 % and 32 % distances up to 30 km respectively). However, in Amazonía and Orinoquía Regions, 87 % and 81 % had to travel more than 90 km - representing very long travel times. For more than 23 % of patients, time to diagnosis was more than 90 days, in Orinoquía, this was above 90 days for 1/3 of patients. Despite relatively short travel distances in the Caribe-Region, for 61 % time to diagnosis exceeded 30 days.

Conclusions: This study identified clear shortcomings in the Colombian Health System related to the quality of childhood cancer-related health care in terms of timeliness, cancer networks, and geographic access. These inequities not only depend on sociodemographic-characteristics and should be intervened upon.
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http://dx.doi.org/10.1016/j.canep.2019.101645DOI Listing
February 2020

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay.

Front Immunol 2019 5;10:2496. Epub 2019 Nov 5.

Department of Tranzo, Tilburg University, Tilburg, Netherlands.

Recently, the 23-valent IgG-assay was suggested as screening assay to identify responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting responders could be more valuable to reduce the number of samples needing serotyping. Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC). Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict responders would have been used. In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.
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http://dx.doi.org/10.3389/fimmu.2019.02496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848064PMC
November 2020

Quantification of T-Cell and B-Cell Replication History in Aging, Immunodeficiency, and Newborn Screening.

Front Immunol 2019 29;10:2084. Epub 2019 Aug 29.

Department of Immunology, Erasmus MC, University Medical Centre, Rotterdam, Netherlands.

Quantification of T-cell receptor excision circles (TRECs) has impacted on human T-cell research, but interpretations on T-cell replication have been limited due to the lack of a genomic coding joint. We here overcome this limitation with multiplex TRG rearrangement quantification (detecting ~0.98 alleles per TCRαβ+ T cell) and the HSB-2 cell line with a retrovirally introduced TREC construct. We uncovered <5 cell divisions in naive and >10 cell divisions in effector memory T-cell subsets. Furthermore, we show that TREC dilution with age in healthy adults results mainly from increased T cell replication history. This proliferation was significantly increased in patients with predominantly antibody deficiency. Finally, Guthrie cards of neonates with Down syndrome have fewer T and B cells than controls, with similar T-cell and slightly higher B-cell replication. Thus, combined analysis of TRG coding joints and TREC signal joints can be utilized to quantify T-cell replication, and has direct applications for research into aging, immunodeficiency, and newborn screening.
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http://dx.doi.org/10.3389/fimmu.2019.02084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730487PMC
September 2020
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