A COVID-19 vaccination program for high-risk children aged 12-17 years in Curacao.

Objective: This study aimed to describe and critically evaluate the COVID-19 vaccination program for high-risk children in Curacao and provide information about important factors such as parents' vaccination hesitancy and effective strategies for communicating and delivering information about vaccination. Methods: This was a cross-sectional study. It was important to identify children aged 12-17 years who were at high risk of severe COVID-19 infection because of the limited medical facilities on the island; children considered to be at high risk were those with diseases such as obesity, hypertension or diabetes mellitus type 2. These children or their caregivers were invited by their pediatricians to be vaccinated as part of a program run by the Public Health Department of Curacao. These high-risk patients were vaccinated between 30 May 2021 and 25 February 2022 in designated child-friendly spaces, with a pediatrician present for guidance and reassurance. Children received the Pfizer-BioNTech COVID-19 vaccine at the recommended dose for their age. The primary outcome was a description and evaluation of the attendance for vaccination. The secondary outcomes were side effects after vaccination for the age groups 12-15 years and 16-17 years. Reasons for refusal or nonadherence were also registered. Results: Altogether 51% (24/47) of those aged 16-17 years who were invited were vaccinated compared with 42% (26/69) of those aged 12-15 years who were invited. Altogether, 46% of these high-risk children were vaccinated compared with 48% of children aged 12-17 years without risk factors. In our population, most patients did not experience any side effects and if they did, the side effects were mild. No cases of myocarditis or pericarditis were observed. A lack of trust in the vaccine and a lack of prioritization of vaccination when scheduling daily activities were important factors in refusal and nonadherence. Conclusions: To organize a successful vaccination program in a small community with limited resources for treating high-risk children it is crucial for medical professionals to provide reliable information. Public health initiatives should focus on assuaging parents' fears about vaccines. In addition, ensuring there is good cooperation between doctors and the Public Health Department can help to make implementation successful. Finally, involving pediatricians and using dedicated areas for vaccinating children can help build trust with parents and caregivers.

An urgent call to raise the bar in oncology.

Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.

Neurologic sequelae of severe chikungunya infection in the first 6 months of life: a prospective cohort study 24-months post-infection.

BACKGROUND: Perinatally chikungunya infected neonates have been reported to have high rates of post-infection neurologic sequelae, mainly cognitive problems. In older children and adults chikungunya does not appear to have sequelae, but data on postnatally infected infants are lacking. METHODS: We performed a prospective, non-controlled, observational study of infants infected before the age of 6 months with a severe chikungunya infection during the 2014-2015 epidemic in Curaçao, Dutch Antilles. Two years post-infection cognitive and motor - (BSID-III) and social emotional assessments (ITSEA) were performed. RESULTS: Of twenty-two infected infants, two died and two were lost to follow up. Eighteen children were seen at follow-up and included in the current study. Of these, 13 (72%) had abnormal scores on the BSID-III (cognitive/motor) or ITSEA. CONCLUSION: In the first study aimed at postnatally infected infants, using an uncontrolled design, we observed a very high percentage of developmental problems. Further studies are needed to assess causality, however until these data are available preventive measure during outbreaks should also include young infants. Those that have been infected in early infancy should receive follow up.

The Impact of Health Risk Communication: A Study on the Dengue, Chikungunya, and Zika Epidemics in Curaçao, Analyzed by the Social Amplification of Risk Framework (SARF).

Epidemics of dengue, chikungunya, and Zika have been threatening the Caribbean. Since risk communication (RC) plays a fundamental role in preventing and controlling diseases understanding how RC works is essential for enabling risk-reducing behavior. This multimethod qualitative study compares news reports with local's and health professional's perspectives, currently lacking in RC research. It was found that RC strategies were obstructed by a lack of governmental structure, organization, and communication. The content analysis showed that the majority of newspaper articles contained negative reporting on the government. Furthermore, this study shows how trust and heuristics attenuate or amplify people's risk perceptions and possibly positively and negatively influence people's risk-reducing behavior. A transcending approach (e.g., structural, cooperative, and multidisciplinary) of the prevention and control of vector-borne diseases and the corresponding RC is recommended.

Zika virus RNA polymerase chain reaction on the utility channel of a commercial nucleic acid testing system.

BACKGROUND: Several countries have implemented safety strategies to reduce the risk of Zika virus (ZIKV) transmission through blood transfusion. These strategies have included nucleic acid amplification testing (NAT) of blood donations. In this study, a new real-time polymerase chain reaction (PCR) assay including internal control for the detection of ZIKV on the cobas omni Utility Channel (UC) on the cobas 6800 system is presented. STUDY DESIGN AND METHODS: PCR conditions and primer/probe concentrations were optimized on the LightCycler 480 instrument. Optimized conditions were transferred to the cobas omni UC on the cobas 6800 system. Subsequently, the limit of detection (LOD) in plasma and urine, genotype inclusivity, specificity, cross-reactivity, and clinical sensitivity were determined. RESULTS: The 95% LOD of the ZIKV PCR assay on the cobas 6800 system was 23.0 IU/mL (95% confidence interval [CI], 16.5-37.5) in plasma and 24.5 IU/mL (95% CI, 13.4-92.9) in urine. The assay detected African and Asian lineages of ZIKV. The specificity was 100%. The clinical concordance between the newly developed ZIKV PCR assay and the investigational Roche cobas Zika NAT test was 83% (24/29). CONCLUSIONS: We developed a sensitive ZIKV PCR assay on the cobas omni UC on the cobas 6800 system. The assay can be used for large-scale screening of blood donations for ZIKV or for testing of blood donors returning from areas with ZIKV to avoid temporal deferral. This study also demonstrates that the cobas omni UC on the cobas 6800 system can be used for in-house-developed PCR assays.

Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis.

BACKGROUND: The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. METHODS AND FINDINGS: As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. CONCLUSIONS: The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

Adaptive coping strategies among individuals living with long-term chikungunya disease: a qualitative study in Curaçao.

OBJECTIVE: Long-term chikungunya disease is characterised by persistent rheumatic symptoms following chikungunya virus infection. As there is no specific treatment available, affected individuals need strategies to adapt. However, research on these is scarce. This study aimed to explore which adaptive coping strategies are employed to manage persistent rheumatic symptoms in daily life. SETTING: The study was conducted in Curaçao. DESIGN AND PARTICIPANTS: An explorative qualitative study was conducted between September and October 2020, among a purposive sample of adults, 19 women and 4 men affected by long-term chikungunya disease. In-depth interviews were semi-structured and transcribed verbatim. The data were analysed using inductive thematic analysis. RESULTS: The disease duration for all participants ranged between 68 and 74 months (6 years). In narrating their experiences of coping with long-term chikungunya disease, four themes were identified: (1) learning to live with the disease; (2) resilience for dealing with pain; (3) maintaining positive self-image and attitude; and (4) coping through spirituality. CONCLUSION: To live with long-term chikungunya disease with dignity in spite of physical pain and discomfort, participants tried to retain a sense of control of oneself and one's lives, to not let the disease take over, focusing on the positive in their lives, and finding strength and remain hopeful. Interventions such as cognitive-behavioural therapy and mindfulness exercises may be effective in strengthening or regain affected individual's sense of competence and control by fostering adaptive coping skills and resilience. Subsequently, these interventions may improve health-related quality of life when rheumatic symptoms persist following chikungunya virus infection.

Pharmaceutical company funding of cancer patient advocacy organizations in the Netherlands.

BACKGROUND: Financial conflicts of interest (FCOI) of medical professionals and associated organizations with pharmaceutical companies (pharma) might contribute to the use of low value oncological treatments. Value criteria for oncological drug approvals in the Netherlands have recently become more stringent leading to objections by cancer patient advocacy organizations (cPAOs). Considering the importance of cPAOs input in cancer patient care we analyzed whether pharma funding of cPAOs occurs in the Netherlands. METHODS: The cPAO websites and available annual reports were evaluated for disclosure of pharma funding for the years 2021 and 2022. Also, data from the Dutch Healthcare Transparency Registry (DHTR) were extracted. RESULTS: Twenty-one of 34 (61.8 %) cPAOs received pharma funding (with 20 registered in the DHTR), and for 13 (29.4 %) cPAOs no reporting of pharma funding could be found. Three of the cPAOs disclosed pharma funding directly on their main website. Online educational material was available from 22 cPAOs on their websites with pharma funding disclosed on the educational material in 5. The total registered amount of pharmaceutical funding was €667,232.00 in 2021 and €536,098.00 in 2022. The median (and interquartile ranges) DHTR registered amount of support per cPAO that received funding in the studied period was €23,799.50 (14,823.75-84,663.30). The most common funding category as defined in the DHTR was project sponsorship. CONCLUSIONS: Financial support by the pharmaceutical industry is common for Dutch cPAOs. Given the importance of cPAOs and their objective input in the societal debate on the availability of cancer drugs, the potential influence of pharma sponsoring should be critically evaluated.

Application of the PHENotype SIMulator for rapid identification of potential candidates in effective COVID-19 drug repurposing.

The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which -by leveraging available transcriptomic and proteomic databases-allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both>96%) the viral effects on cellular host-immune response, resulting in specific cellular SARS-CoV-2 signatures and ii) utilize these cell-specific signatures to identify promising repurposable therapeutics. Powered by this tool, coupled with domain expertise, we identify several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential druggable targets in COVID-19 pathogenesis.

N-acetylcysteine reduces oxidative stress in sickle cell patients.

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSß(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

[Financial conflict of interest and anti-cancer drugs: Why the NTVG's stance to exclude pharma-advertisement is of importance.] / Financiële belangen en oncologische geneesmiddelen.

The number of new oncological treatments is increasing rapidly, even though many offer limited benefit to patients. In these cases, the scientific research leading to approvals is marred by shortcomings. Nonetheless, many drugs of limited value are approved by regulatory agencies. One of the factors contributing thereto is financial conflict of interest (FCI) with the pharmaceutical industry (Pharma). This occurs at different levels, including researchers, opinion leaders and editors of medical journals. FCI contributes to patient exposure to treatments that offer limited or no benefit and to unjust spending of valuable resources while providing large revenues for Pharma. The important step of the 'NederlandsTijdschriftvoorGeneeskunde' (NTVG) to omit all pharmaceutical advertisement as well as advertisement for pharmaceutical industry sponsored medical education sends an important signal and is a first step to revalue the important relationship with the pharmaceutical industry.

Bacterial Contamination of Ultrasound and Stethoscope Surfaces in Low- and High-Resource Settings.

Point-of-care ultrasound is an accurate diagnostic and monitoring tool. Its increasing affordability, portability, and versatility make it an excellent component of standard clinical evaluation alongside the stethoscope. However, like the stethoscope, ultrasound carries risks of surface contamination and potential cross-infection. In this international observational study, we compared the surface contamination of ultrasound equipment to stethoscopes in two medical centers: a tropical low-resource hospital and academic high-resource hospital. Ultrasound equipment and coupling gel had similar prevalence of microbial surface contamination compared with observed stethoscopes. Most microbes were commensal Gram-positive, but some were opportunistic and pathogenic microbes (such as Escherichia coli and Staphylococcus aureus). In conclusion, it is crucial to appreciate and reduce the risk of ultrasound device contaminations. When ultrasound is used bedside, similar to stethoscopes, conscientious hygiene measures are equally fundamental.

Developing quality indicators for the care of HIV-infected pregnant women in the Dutch Caribbean.

BACKGROUND: Effective interventions to prevent mother-to-child HIV transmission (PMTCT) exist and when properly applied reduce the risk of vertical HIV transmission. As part of optimizing PMTCT in the Dutch Caribbean we developed a set of valid and applicable indicators in order to assess the quality of care in HIV-infected (pregnant) women and their newborns. METHODS: A multidisciplinary expert panel of 19 experts reviewed and prioritized recommendations extracted from locally used international PMTCT guidelines according to a 3-step-modified-Delphi procedure. Subsequently, the feasibility, sample size, inter-observer reliability, sensitivity to change and case mixed stability of the potential indicators were tested for a data set of 153 HIV-infected women, 108 pregnancies of HIV-infected women and 79 newborns of HIV-infected women in Aruba, Curaçao and St Maarten from 2000 to 2010. RESULTS: The panel selected and prioritized 13 potential indicators. Applicability could not be tested for 4 indicators regarding HIV-screening in pregnant women because of lack of data. Four indicators performed satisfactorily for Curaçao ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'intrapartum antiretroviral therapy and infant prophylaxis if antepartum antiretroviral therapy was not received', 'scheduled caesarean delivery') and 3 for St Maarten ('monitoring CD4-cell count', 'monitoring HIV-RNA levels', 'discuss and provide combined antiretroviral therapy to all HIV-infected pregnant women') whilst none for Aruba. CONCLUSIONS: A systemic evidence-and consensus-based approach was used to develop quality indicators in 3 Dutch Caribbean settings. The varying results of the applicability testing accentuate the necessity of applicability testing even in, at first, comparable settings.

Rapid Identification of Druggable Targets and the Power of the PHENotype SIMulator for Effective Drug Repurposing in COVID-19.

The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with very few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which - by leveraging available transcriptomic and proteomic databases - allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both > 96%) the viral effects on cellular host-immune response, resulting in a specific cellular SARS-CoV-2 signature and ii) utilize this specific signature to narrow down promising repurposable therapeutic strategies. Powered by this tool, coupled with domain expertise, we have identified several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential new druggable targets in COVID-19 pathogenesis.

Clinical Leadership as an Agent for Change: A Health System Improvement Intervention in Curaçao.

INTRODUCTION: The healthcare system in Curaçao is complex, fragmented, and poorly organized and typifies a system in a resource-limited environment. Deficits in competencies and local cultural barriers are factors that hinder sustainable healthcare in such settings and a failure to meet WHO sustainable development goals. This study reports the potential cost-effectiveness and improved health outcomes of the first stage of a healthcare improvement project. The intervention, which is a multidisciplinary team-based leadership training program (MLP), reflects a promising strategy to tackle local healthcare needs. METHODS: A Multidisciplinary group of healthcare professionals in St. Elisabeth hospital, Curaçao, was selected to 1) participate in the MLP and 2) co-design a healthcare pathway on the management of decubitus ulcers. Using a qualitative research methodology, we conducted interviews to assess the perceived leadership growth, teamwork, and the barriers to the introduction of the new care pathway in their setting. Six themes were identified that explained the perceived leadership development and interprofessional collaboration. These included 1) Professional background, 2) Healthcare pathway design, 3) Resources, 4) Personal development, 5) Collaboration 6) Execution. CONCLUSION/IMPLICATION: The participants valued the interdisciplinary approach of this health improvement project and acknowledged the added value of a training program that also addressed personal growth. This study shows how MLPs for health professionals can also serve as catalysts for health improvement efforts in resource-limited environments.

ANERGY TO SYNERGY-THE ENERGY FUELING THE RXCOVEA FRAMEWORK.

We write to introduce our novel group formed to confront some of the issues raised by the COVID-19 pandemic. Information about the group, which we named "cure COVid for Ever and for All" (RxCOVEA), its dynamic membership (changing regularly), and some of its activities-described in more technical detail for expert perusal and commentary-are available upon request.

Circulating endothelial cells: a potential parameter of organ damage in sickle cell anemia?

Objective laboratory tools are needed to monitor developing organ damage in sickle cell disease (SCD). Circulating endothelial cells (CECs) are indicative of vascular injury. We determined whether elevated CEC can be detected in asymptomatic SCD with the CellSearch system and whether the CEC count is related to clinical and blood-based biomarkers of disease severity. Fifteen consecutive clinically asymptomatic HbSS patients and 15 matched HbAA controls were analyzed for CEC counts, laboratory parameters of disease severity (Hb, leukocyte counts, HbF%), plasma levels of markers for endothelial activation (sVCAM-1, VWF:Ag) and of endogenous inhibitors of nitric oxide synthase (asymmetrical dimethylarginine [ADMA]). CEC counts were significantly higher in patients (12 cells/mL, IQR 8-29) as compared to controls (4 cells/mL, 3-10) (P=0.007). CEC counts were significantly higher in patients with pulmonary hypertension (PHT) (P=0.015), and increased with increasing number of affected organs (0-4 involved organs, P=0.002). No significant correlations between CEC and any other laboratory parameter were detected. In conclusion, CECs could prove to be an important new tool for assessing developing vasculopathy and organ damage in SCD.

Health care transformation in a resource-limited environment: exploring the determinants of a good climate for change.

PURPOSE: In a continued effort to improve the health care services, a project was set up to develop and implement a care pathway for the effective management of pressure ulcers in the St Elisabeth Hospital in Curaçao, the Dutch Caribbean. To ensure the effective implementation of our intervention, we decided to investigate what factors define the implementation climate of a health care institution within a resource-limited environment. METHODS: We used a participatory tool approach in this study, where a mixed team of health professionals worked on two parts of a health improvement project, namely: 1) workforce leadership development through a clinical leadership training program; and 2) health care quality improvement through the pressure ulcer care pathway development. In-depth interviews were held with ten participants to gain insight into their experiences of the implementation climate in the hospitals and inductive analysis was used to identify the (sub)themes. RESULTS: Identified themes that described the implementation climate included: 1) the attitude of staff toward policy changes; 2) vision of the organization; 3) collaboration; 4) transparency and communication; 5) personal development; and 6) resources. These factors were interrelated and associated with several potential consequences such as loss of motivation among staff, loss of creativity to solve issues, the emergence of the feeling "us" vs "them", short-term solutions to problems, and a sense of suspicion/frustration among staff members. CONCLUSION: From this study, positive subconstructs for a favorable implementation climate in a hospital organization were lacking and those that were identified were suboptimal. The inability to satisfy all the subconstructs seemed to be the consequence of insufficient resources and infrastructure within the current health system. A favorable implementation climate in a resource-limited environment is closely tied to the availability of health care resources and infrastructure.