The safety of pathogen-reduced platelet transfusions in critically ill term and preterm neonates.

BACKGROUND AND OBJECTIVES: Platelet transfusions carry an important risk of infection transmission. The Mirasol Pathogen Reduction Technology system for platelets uses riboflavin and UV light to introduce irreparable lesions into nucleic acids, thereby inhibiting pathogen replication and inactivating white blood cells. The objective of this study is to evaluate the safety of pathogen-reduced platelet transfusions (PRPTs) in critically ill infants in a neonatal intensive care unit (NICU) in the Caribbean. MATERIALS AND METHODS: We conducted a descriptive retrospective study of the use of Mirasol PRPTs in patients admitted to the NICU of the general hospital in Curaçao from February 2016 to April 2023. RESULTS: A total of 208 PRPTs were administered to 46 patients (median [range] transfusions per patient: 3 [1-24]). Three patients were born term, and 43 were born preterm (median [range] gestational age: 27 4/7 weeks [24 6/7-36 6/7]). PRPTs were well-tolerated and no complications occurred, especially no signs of haemolysis nor any signs of new infection within 24 h after transfusion. Twenty-one of 46 patients (46%) died during their admittance. None of the deaths were deemed related to PRPT. CONCLUSION: Mirasol PRPT appears to be safe for use in critically ill neonates, including extremely preterm neonates.

Contexts motivating protective behaviours related to Aedes-borne infectious diseases in Curaçao.

BACKGROUND: Aedes aegypti, the vector of arboviral diseases such as dengue and Zika virus infections, is difficult to control. Effective interventions must be practicable, comprehensive, and sustained. There is evidence that community participation can enhance mosquito control. Therefore, countries are encouraged to develop and integrate community-based approaches to mosquito control to mitigate Aedes-borne infectious diseases (ABIDs). Health professionals must understand the contexts motivating individuals' behaviour to improve community participation and promote behavioural change. Therefore, this study aimed to determine how contexts shaped individuals' protective behaviours related to ABIDs in Curaçao. METHODS: From April 2019 to September 2020, a multi-method qualitative study applying seven (n = 54) focus group discussions and twenty-five in-depth interviews with locals was performed in CuraÒ«ao. The study was designed based on the Health Belief Model (HBM). Two cycles of inductive and deductive coding were employed, and Nvivo software was used to manage and analyse the data. RESULTS: In this study, low media coverage (external cue to action) and limited experience with the symptoms of ABIDs (internal cue to action) were linked with a low perceived susceptibility and severity of ABIDs (low perceived threat). The low perceived threat was linked with reduced health-seeking behaviour (HSB) to prevent and control ABIDs. We also found that the perceived barriers outweigh the perceived benefits of ABID prevention and control interventions, obstructing HSB. On the one hand, insufficient knowledge reduced self-efficacy but contrary to expected, having good knowledge did not promote HSB. Lastly, we found that our participants believe that they are responsible for preventing ABIDs (internal locus of control) but at the same time indicated that their success depends on the efforts of the community and the health system (external locus of control). CONCLUSIONS: This study used the HBM to explain individual changes in HSB concerning ABIDs prevention and control in Curaçao. We can conclude that the perceived threat (perceived susceptibility and severity) and perceived barriers played an essential role in changing HSB. Health professionals must consider these two concepts' implications when designing a bottom-up approach for ABIDs control; otherwise, community participation will remain minimal.

"What will the doctor give me, the same painkiller?": a qualitative study exploring health-care seeking and symptoms self-management among patients for the treatment of long-term chikungunya disease, in Curaçao.

BACKGROUND: Long-term chikungunya disease, characterized by persistent disabling rheumatic symptoms, including poly-arthralgia/arthritis of severe pain intensity, can persist for years after infection with the re-emerging mosquito-borne chikungunya virus. Although persistent symptoms and pain severity are important determinants of health-care seeking and self-management of symptoms, research on these in relation to long-term chikungunya disease is scarce. This study aimed to explore the perceived benefits and perceived barriers concerning health-care seeking, based on the Health Belief Model, and the symptoms self-management strategies used for health outcome improvement among individuals affected by long-term chikungunya disease. METHODS: An exploratory qualitative descriptive study was conducted with 20 purposively selected adults (17 females and 3 males) with persistent rheumatic symptoms, recruited from an ongoing longitudinal chikungunya cohort, in Curaçao. Semi-structured interviews were carried out, audio-recorded, and transcribed. An iterative coding process was used for themes identification through inductive thematic analyses. RESULTS: No perceived benefits in health-care seeking were reported. Identified themes in relation to perceived barriers were: (1) health-care seeking at disease onset; (2) general practitioners (GPs) perceptions and awareness of persistent symptoms; (3) challenges for medical referrals and support; (4) no validation of symptoms and challenges accessing therapy; (5) health system restrictions; and (6) social stigmatization of psychological help. These perceived barriers have led participants to self-manage persistent symptoms. Over-the-counter pharmacological and/or non-pharmacological treatments were used without consulting GPs. Identified themes were: (1) self-medication of symptoms; and (2) self-management true non-pharmacological treatments. CONCLUSIONS: To promote the benefits of long-term health-care seeking and subsequently reduce the possible harmful use of analgesics, a collaborative physician-patient therapeutic relationship need to be encouraged. To facilitate this, important shifts may be needed in chikungunya sequalae education of both patients and health-care professionals, and policy makers need to revise health systems for the long-term provision of multidisciplinary care to achieve beneficial health outcomes in long-term chikungunya disease.

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.

The clinical manifestation and the influence of age and comorbidities on long-term chikungunya disease and health-related quality of life: a 60-month prospective cohort study in Curaçao.

BACKGROUND: Persistent rheumatic symptoms and its impact on health-related quality of life (QoL), induced by the Indian Ocean Lineage (IOL) chikungunya virus (CHIKV) genotype have been widely studied. In 2014, a major CHIKV outbreak of the Asian genotype occurred in Curaçao, after which we established a longitudinal cohort in 2015, to follow the long-term CHIKV sequalae. Currently, the long-term clinical manifestations and its impact on QoL induced by the Asian CHIKV genotype, followed prospectively through time, and the association of age and comorbidities with rheumatic symptoms persistence, 60 months (M60) after disease onset is unknown. METHODS: The cohort of 304 laboratory confirmed patients were followed prospectively in time at 3-16 months (M3-16), 30 months (M30), and M60 after disease onset. Demographic and clinical characteristics, and the 36-item short-form survey (SF-36) QoL status were collected through questionnaires. At M60, QoL scores were compared to general population (CHIK-) norms. RESULTS: A total of 169 (56%) patients participated (74.6% female, mean age 56.1 years) at all time points, 107 (63%) were classified as recovered and 62 (37%) as affected. The affected patients reported an increase in the prevalence of arthralgia (P .001) and arthralgia in the lower extremities (P < .001), at M30 compared to M3-16. At M60, in comparison to recovered patients, affected patients reported a higher prevalence of recurrent rheumatic symptoms of moderate to severe pain, irrespective of age and comorbidities, and a higher prevalence of non-rheumatic symptoms (P < .001). Arthralgia in the upper (odds ratio (OR): 4.79; confidence interval (CI): 2.01-11.44; P < .001) and lower (OR: 8.68; CI: 3.47-21.69; P < .001) extremities, and headache (OR: 3.85; CI: 1.40-10.54; P = .009) were associated with being affected. The SF-36 QoL scores of the recovered patients were less impaired over time compared to the QoL scores of the affected patients. At M60, the QoL scores of the recovered patients were comparable to the CHIK- QoL scores. CONCLUSIONS: Rheumatic and non-rheumatic symptoms, and QoL impairment may persist, 60 months following infection with the Asian CHIKV genotype, similar to the IOL genotype disease sequelae. Further research is needed to follow the clinical manifestations and QoL impact of each CHIKV genotype.

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.

SARS-CoV-2 outbreak on the Caribbean islands of the Dutch Kingdom: a unique challenge.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic progresses, countries are depending on one another to acquire knowledge regarding effective measures to contain the virus. Public health measures to suppress transmissions have proven successful in Singapore, Hong Kong and Taiwan. Implementing and adhering to these interventions is challenging, with governments struggling to find a balance between necessary mitigation and suppression strategies, and interruptions of social-economic activities. While large high-income countries are struggling to keep their health systems and economies moving forward, small island developing states are facing even more significant challenges. Many Caribbean islands, including the six islands within the Dutch Kingdom, have been quick to implement stringent public health measures, yet they are facing unique challenges.

A medida que avanza la pandemia de síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), los países dependen unos de otros para adquirir conocimientos sobre las medidas eficaces para contener el virus. Las medidas de salud pública dirigidas a suprimir la transmisión han demostrado su eficacia en Singapur, Hong Kong y Taiwán. La aplicación y la adhesión a esas intervenciones representa un desafío, ya que los gobiernos necesitan encontrar un equilibrio entre las estrategias de mitigación y supresión necesarias y la interrupción de las actividades socioeconómicas. Al tiempo que los países grandes y de altos ingresos luchan por mantener sus sistemas de salud y sus economías en funcionamiento, los pequeños estados insulares en desarrollo se enfrentan a retos aún más importantes. Muchas islas del Caribe, incluidas las seis islas del Reino de los Países Bajos, han aplicado medidas de salud pública estrictas de manera rápida, pero se enfrentan a desafíos singulares.

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.

Spatial and temporal trends of dengue infections in Curaçao: A 21-year analysis.

Dengue viruses are a significant global health concern, causing millions of infections annually and putting approximately half of the world's population at risk, as reported by the World Health Organization (WHO). Understanding the spatial and temporal patterns of dengue virus spread is crucial for effective prevention of future outbreaks. By investigating these patterns, targeted dengue surveillance and control measures can be improved, aiding in the management of outbreaks in dengue-affected regions. Curaçao, where dengue is endemic, has experienced frequent outbreaks over the past 25 years. To examine the spatial and temporal trends of dengue outbreaks in Curaçao, this study employs an interdisciplinary and multi-method approach. Data on >6500 cases of dengue infections in Curaçao between the years 1995 and 2016 were used. Temporal and spatial statistics were applied. The Moran's I index identified the presence of spatial autocorrelation for incident locations, allowing us to reject the null hypothesis of spatial randomness. The majority of cases were recorded in highly populated areas and a relationship was observed between population density and dengue cases. Temporal analysis demonstrated that cases mostly occurred from October to January, during the rainy season. Lower average temperatures, higher precipitation and a lower sea surface temperature appear to be related to an increase in dengue cases. This effect has a direct link to La Niña episodes, which is the cooling phase of El Niño Southern Oscillation. The spatial and temporal analyses conducted in this study are fundamental to understanding the timing and locations of outbreaks, and ultimately improving dengue outbreak management.

"It's very saddening, you keep on wondering when the symptoms will be over": A qualitative study exploring the long-term chikungunya disease impact on daily life and well-being, 6 years after disease onset.

BACKGROUND: Long-term chikungunya is a mosquito-borne disease, characterized by disabling rheumatic symptoms persisting for years, after infection with the chikungunya virus. Previous studies focused on assessing the well-being of affected individuals from a quantitative perspective using generic instruments, and have reported physical and psychological impairment. However, a common critique is that generic instrument's structured responses and pre-defined health domains selected by health professionals, may not capture the full extent of well-being impairment experienced by patients. This study aimed to explore in-depth to which extent long-term chikungunya disease impacts daily living and the physical, psychological, and social well-being from the experiences and perspective of affected individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using open-ended questions, in-depth interviews were conducted with 20 purposively selected individuals with long-term chikungunya disease, in Curaçao. Interview audio-recordings were transcribed verbatim. The data were thematically analyzed. Living with persistent rheumatic symptoms affected the participant's daily living and well-being in several ways: experience of physical impact (restricted physical functioning and limitations in activities of daily life); experience of psychological impact (altered emotional state, fear of walking and running, psychosocial aspects of footwear adaptations, and uncertainty about disease progression and future health); and experience of social impact (social isolation and impaired relational maintenance, social dependency, challenges of social support, at-work productivity loss, and giving up leisure activities after work). CONCLUSIONS/SIGNIFICANCE: This study, the first of its kind, indicated that the adverse impact of long-term chikungunya disease is currently underreported. The persistent rheumatic symptoms had a negative effect on functional ability, which in turn impacted broad aspects of daily life and well-being, beyond what is captured by generic instruments. In the view of the findings, physical exercise programs including manual therapy, aerobics, resistance and stretching exercises, and orthopaedic footwear interventions in a multidisciplinary patient-centred approach may improve physical function and subsequently overall well-being.

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.