No (true) right to die: barriers in access to physician-assisted death in case of psychiatric disease, advanced dementia or multiple geriatric syndromes in the Netherlands.

Even in the Netherlands, where the practice of physician-assisted death (PAD) has been legalized for over 20 years, there is no such thing as a 'right to die'. Especially patients with extraordinary requests, such as a wish for PAD based on psychiatric suffering, advanced dementia, or (a limited number of) multiple geriatric syndromes, encounter barriers in access to PAD. In this paper, we discuss whether these barriers can be justified in the context of the Dutch situation where PAD is legally permitted for those who suffer unbearably and hopelessly as a result of medical conditions. Furthermore, we explore whether there are options to address some of the barriers or their consequences, both within the Dutch legal framework or by adjusting the legal framework, and whether these options are feasible. We conclude that although there are insufficient arguments to overrule the doctor's freedom of conscience in the Netherlands, there are ways to address some of the barriers, mainly by offering support to doctors that would be willing to support a request. Moreover, we believe it is morally required to reduce or mitigate where possible the negative consequences of the barriers for patients, such as the long waiting time for those who suffer from psychiatric disorders, because it is unlikely the adjustments suggested to the system will ensure reasonable access for these patient groups.

Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021-January 2022.

BACKGROUND: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. METHODS: National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin. RESULTS: VE against COVID-19 mortality was > 90 % for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80 % at 7-8 months post-primary series for most groups, and around 60 % for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to > 85 % in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups. CONCLUSION: At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.

Protection of COVID-19 vaccination and previous infection against Omicron BA.1, BA.2 and Delta SARS-CoV-2 infections.

Given the emergence of the SARS-CoV-2 Omicron BA.1 and BA.2 variants and the roll-out of booster COVID-19 vaccination, evidence is needed on protection conferred by primary vaccination, booster vaccination and previous SARS-CoV-2 infection by variant. We employed a test-negative design on S-gene target failure data from community PCR testing in the Netherlands from 22 November 2021 to 31 March 2022 (n = 671,763). Previous infection, primary vaccination or both protected well against Delta infection. Protection against Omicron BA.1 infection was much lower compared to Delta. Protection was similar against Omicron BA.1 compared to BA.2 infection after previous infection, primary and booster vaccination. Higher protection was observed against all variants in individuals with both vaccination and previous infection compared with either one. Protection against all variants decreased over time since last vaccination or infection. We found that primary vaccination with current COVID-19 vaccines and previous SARS-CoV-2 infections offered low protection against Omicron BA.1 and BA.2 infection. Booster vaccination considerably increased protection against Omicron infection, but decreased rapidly after vaccination.

Exploring doctors' reasons for not granting a request for euthanasia: a mixed-methods study.

BACKGROUND: In a growing number of jurisdictions, physician-assisted death (PAD) is now an established part of medical care. Although PAD is allowed under certain criteria in The Netherlands, physicians can always refuse a request. The Euthanasia Expertise Centre (EEC) offers PAD to patients whose request was declined in circumstances where their own physician could have satisfied the legal criteria. The number of requests reaching EEC has increased, suggesting the threshold for treating physicians to refer patients to EEC has become lower. AIM: To explore the reasons of physicians for not granting a request for PAD and/or referring a patient to EEC, and any needs physicians may have in handling requests for PAD. DESIGN & SETTING: Survey and interviews among Dutch physicians in The Netherlands. METHOD: A questionnaire was sent to 500 physicians who declined a request for PAD and whose patient subsequently requested PAD at EEC. This was followed by a qualitative study, in which in-depth interviews were held with 21 of the physicians who responded to the survey. RESULTS: Doctors were identified as those who had objections on principle, or with other reasons for refusing a request for PAD and/or to refer the patient to EEC. These reasons were mostly related to concerns about complying with the due care criteria for PAD, or to difficulties with PAD in specific patient groups. In these cases they often valued support from another healthcare professional. CONCLUSION: For patients of physicians with objections on principle against PAD, EEC offered a good solution. Doctors who struggle with whether they can comply with the legal criteria might benefit from peer support.

Wish for euthanasia persists for at least one year after the request was declined by Euthanasia Expertise Center.

BACKGROUND: Euthanasia Expertise Center (EEC) in the Netherlands provides euthanasia or physician-assisted suicide for patients who meet all requirements of the Dutch Euthanasia Law, but whose treating physician declined their request. Little is known about how life continues for a patient after a request for physician-assisted death (PAD) is also declined by EEC. OBJECTIVE: To follow-up patients whose request for PAD was declined at EEC. METHODS: Between December 2016 and January 2020, 66 patients were prospectively followed for one year after their request was declined. Their general well-being and health, persistence of the wish for PAD, and mortality was measured by means of a questionnaire administered after three, six and 12 months. Furthermore, information was extracted from the patient's medical record. FINDINGS: More than half (58%) of the included patients suffered from an accumulation of old-age complaints. In the year after the request was declined, 15 patients (23%) died, three of whom committed suicide. Almost all patients who were alive after one year, persisted in their wish for PAD. Moreover, they were often not doing well. CONCLUSIONS: Considering that EEC is a last resort for those who were not granted PAD elsewhere, and that the wish for PAD persists, aftercare services should be provided to people whose request has been declined.

A systematic review of the burden of pertussis disease in infants and the effectiveness of maternal immunization against pertussis.

Introduction Infants too young to be fully immunized are the most vulnerable to severe pertussis disease. To close this susceptibility gap, passive infant immunization through vaccination of pregnant women against pertussis was first introduced in 2011 in the United States and has been extended since then to more than 40 countries. Areas covered We conducted two systematic literature searches to describe the worldwide burden of pertussis disease in infants <6 months of age since 2005, and the effectiveness and impact of maternal pertussis vaccination in preventing infant pertussis since 2011. Expert opinion Pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks. Virtually all pertussis deaths occurred in this age group. Data from Africa, Eastern Mediterranean, and Asia were limited, but suggest a similar or higher disease burden than in Europe or the Americas. Estimates of effectiveness of second/third trimester pertussis vaccination in preventing pertussis disease in <2-3 months old infants were consistently high (69%-93%) across the observational studies reviewed, conducted in various settings with different designs. Maternal vaccination programs appear to be achieving their goal of reducing the burden of disease in very young infants. Plain language summary What is the context? Pertussis, also known as whooping cough, is a highly contagious disease of the respiratory tract. Infants too young to be fully vaccinated are at the highest risk of severe pertussis disease, hospitalization, and death. Vaccinating pregnant women against pertussis with a Tdap vaccine is recommended in more than 40 countries as a safe and effective strategy to protect infants for the first months of life. What is new? This review summarizes recent literature describing the burden of pertussis disease in infants worldwide prior to the introduction of maternal vaccination programs; pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks. Immunization of pregnant women with a Tdap vaccine can prevent about 70-90% of pertussis disease and up to 90.5% of pertussis hospitalizations in infants under 3 months of age. What is the impact? Limited available data suggest that incidence rates of pertussis disease after the introduction of Tdap maternal immunization have declined in infants. Current knowledge supports the implementation of Tdap maternal immunization programs.

Outbreaks of meningococcal meningitis in non-African countries over the last 50 years: a systematic review.

BACKGROUND: Meningococcal disease is caused by the bacteria Neisseria meningitidis, leading to substantial mortality and severe morbidity; with serogroups A, B, C, W135, X and Y most significant in causing disease. An outbreak is defined as multiple cases of the same serogroup occurring in a population over a short time-period. A systematic review was performed to gain insight into outbreaks of meningococcal disease and to describe the temporal pattern over the last 50 years in non-African countries. METHODS: PubMed and EMBASE were searched for English-language publications on outbreaks of meningococcal disease in non-African countries between January 1966 and July 2017, with an additional grey literature search. Articles and reports were considered eligible if they reported confirmed meningococcal outbreak cases, included the region, number of cases, and the start and end dates of the outbreak. Data on outbreaks was stratified by geographical region in accordance with the World Health Organization (WHO) regional classification, and case-fatality rates (CFRs) were calculated. RESULTS: Of the identified publications, 3067 were screened and 73 included, reporting data from 83 outbreaks. The majority of outbreaks were identified in the regions of the Americas (41/83 outbreaks), followed by the European region (30/83 outbreaks). In each of the Western Pacific, Eastern Mediterranean, and South-East Asian regions there were <10 outbreaks reported. The predominant serogroup in the majority of outbreaks was serogroup C (61%), followed by serogroup B (29%), serogroup A (5%) and serogroup W135 (4%). Outbreaks showed a peak in the colder months of both the Northern and Southern Hemispheres. Of the 54 outbreaks where CFR was calculable for all outbreak cases, it ranged from 0%-80%. CONCLUSIONS: These data present a retrospective view of the patterns for meningococcal disease outbreaks in non-African countries, and provide valuable data for monitoring future changes in disease epidemiology and informing preventive measures.

The immunogenicity of GSK's recombinant hepatitis B vaccine in children: a systematic review of 30 years of experience.

INTRODUCTION: The World Health Organization recommends hepatitis B virus (HBV) vaccines to be included in national immunization schedules everywhere, and has adopted the strategic goal of halting viral hepatitis as a major public health threat by 2030, under which vaccination plays a major role. Engerix™ B (GSK HepB, GSK, Belgium) was the first recombinant HBV vaccine to be licensed, and marked its 30th anniversary in 2016. Areas covered: We conducted a systematic review of the literature summarizing 30 years of immunogenicity and safety data for GSK HepB in children and adolescents. Expert commentary: Primary 3-dose vaccination of healthy infants and children, including infants born to HBsAg-positive mothers, using the standard 0, 1, 6 month schedule was associated with seroprotection rates ≥96.0%. In high-risk infants, vaccine efficacy at year 5 was 96.0% after 3-dose priming in infancy and immunoglobulin at birth. Lower seroprotection rates were observed in children with severe underlying disease including human immunodeficiency virus infection and cancer. GSK HepB had a clinically acceptable safety profile in all of the populations studied. HBV vaccines have demonstrated long-term impacts on rates of fulminant hepatitis, chronic liver disease and hepatocellular carcinoma. GSK HepB will continue to contribute to global HBV control for the foreseeable future.

The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.

INTRODUCTION: Engerix B (GSK HepB, GSK, Belgium) was the first recombinant hepatitis B virus vaccine to be licensed, and marked its 30th anniversary in 2016. Vaccination of adult populations against HBV is usually implemented on a risk-based approach with varying degrees of success. Confirmation of ongoing vaccine effectiveness requires monitoring the performance of HBV immunization as reported in individual studies, using systematic methods. Areas covered: We conducted a systematic review of the literature to summarize 30 years of immunogenicity and safety data for GSK HepB in adult populations. Expert commentary: Primary 3-dose vaccination of healthy individuals is generally associated with seroprotection rates of 90% or more, although seroprotection decreases with older age. Accelerated 0, 1, 2-month or 0, 7 and 21-day schedules require the recommended booster dose to achieve similar rates of seroprotection. Lower rates of seroprotection were also observed in adults with underlying chronic disease and with a weakened immune system. GSK HepB had a clinically acceptable safety profile in all of the populations studied, including individuals with underlying co-morbidities and immunosuppression. GSK HepB will continue to contribute to global HBV control for the foreseeable future. Further investigation is needed into how to optimize seroprotection in less immune-competent groups.

Benefits and harms of breast cancer screening with mammography in women aged 40-49 years: A systematic review.

Early detection of breast cancer through screening can lower breast cancer mortality rates and reduce the burden of this disease in the population. In most western countries, mammography screening starting from age 50 is recommended. However, there is debate about whether breast cancer screening should be extended to younger women. This systematic review provides an overview of the evidence from RCTs on the benefits and harms of breast cancer screening with mammography in women aged 40-49 years. The quality of the evidence for each outcome was appraised using the GRADE approach. Four articles reporting on two different trials-the Age trial and the Canadian National Breast Screening Study-I (CNBSS-I)-were included. The results showed no significant effect on breast cancer mortality (Age trial: RR 0.93 (95% CI 0.80-1.09); CNBSS-I: HR 1.10 (95% CI 0.86-1.40)) nor on all-cause mortality (RR 0.98, 95% CI 0.93-1.03) in women aged 40-49 years offered screening. Among regularly attending women, the cumulative risk of experiencing a false-positive recall was 20.5%. Over-diagnosis of invasive breast cancer at 5 years post-cessation of screening for women aged 40-49 years was estimated to be 32% and at 20 years post-cessation of screening to be 48%. Including ductal carcinoma in situ, these numbers were 41% and 55%. Based on the current evidence from randomised trials, extending mammography screening to younger age groups cannot be recommended. However, there were limitations including relatively low sensitivity of screening and screening attendance, insufficient power, and contamination, which may explain the nonsignificant results.