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The role of the thymus in allogeneic haematopoietic stem cell transplantation
Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat an increasing number of congenital and acquired disorders of the haematopoietic system. Even though cytoreductive conditioning regimens vary in intensity, all clinically used protocols invariably cause side effects that compromise transiently or long-term the response of the natural and the adaptive immune systems. However, in the context of the reconstruction of immunity, the generation of naïve T cells constitutes a slow process, and requires a functionally competent thymus. Unfortunately, regular thymic function is frequently suppressed by transplant-related toxicities. Most notably, graft-versus-host disease (GVHD) causes a state of posttransplantation immune deficiency. Here we discuss preclinical allogeneic HSCT models and clinical observations that have contributed to a detailed understanding of the cellular and molecular mechanisms responsible for the thymic dysfunction caused by acute GVHD. An in-depth knowledge of the mechanisms that control regular thymopoiesis and, conversely, affect thymus function is expected to provide the factual basis for the design of innovative therapies to recover T-cell numbers and function following allogeneic HSCT.
Swiss recommendations on driving ability in patients with diabetes mellitus
Most people with diabetes mellitus operate motor vehicles safely without creating any meaningful risk on the road for themselves or others. A diagnosis of diabetes is, in itself, inadequate for determining a person’s driving capability or safety. Diabetes-related traffic accidents are rare for most drivers with diabetes mellitus and occur less frequently than for many other diseases that can impair driving performance and that are tolerated by society. The incidence of hypoglycaemia, which impairs the ability to drive, severe retinopathy (including macular oedema) or cataract formation affecting visual acuity required to drive a motor vehicle, and peripheral neuropathy, which can severely impair sensation in the feet, is not so common as to justify restricting driving privileges for all drivers with diabetes mellitus.
In recent years, several pharmacological and technological innovations have revolutionised diabetes care. Continuous glucose monitoring system (CGMS) technology has only recently become increasingly integrated into diabetes therapy. Today, except for insulin, none of the treatments recommended for type 2 diabetes mellitus causes hypoglycaemia, and the risk of hypoglycaemia with ultra-long-acting insulins is lower. As a result, recommendations for driving motor vehicles have had to be adjusted. Since hypoglycaemia is the greatest risk factor for impaired driving ability, the latest technology (CGMS coupled with hybrid closed-loop insulin pumps) can reduce the number of hypoglycaemic events and blood glucose fluctuations. In addition, HbA1c and time in target range can be improved. Patients with type 1 diabetes mellitus are now, in exceptional cases, allowed to be licensed in higher vehicle categories. With the analysis of CGMS data, an objective assessment of the frequency of hypoglycaemia is now possible; this was previously only partially possible with blood glucose logs. Patients who are treated with insulin should use a CGMS. This also applies to gestational diabetes and diabetes during pregnancy. Since these systems warn of impending hypoglycaemia, they will also improve road safety, and the safety margin for blood glucose, previously set at 5 mmol/l, can be lowered to 4 mmol/l. For CGMS users, blood glucose measurements every 2 hours while driving are no longer necessary.
Non-invasive prenatal testing is not a substitute for first trimester ultrasound screening
The ultrasound examination in the first trimester is a crucial tool in prenatal diagnostics. Its primary aim is the early detection of fetal structural anomalies with the option to assess the risk for the common fetal trisomies (in Switzerland: “Ersttrimestertest”). The latter is achieved by combining ultrasound data with biochemical blood tests.
In addition to chromosomal diagnostics, the first-trimester ultrasound plays an essential role in evaluating pregnancy risks as well as the overall health of the fetus. This method is non-invasive, safe and effective, offering invaluable information to both healthcare professionals and expectant parents that is critical for further pregnancy care.
The introduction and wide-spread use of another, molecular test, NIPT (“non-invasive prenatal testing”) should be seen as a useful additional option to, not a substitute for first trimester ultrasound. NIPT has high detection rates for “the common trisomies”, but, in isolation, is insufficient for comprehensive early fetal assessment.
An approach to implementing patient and public involvement in investigator-initiated clinical trials
As patient and public involvement (PPI) in academic clinical research, especially clinical trials, is gaining recognition, including acceptance and implementation, questions arise about how to establish an effective “basic framework for PPI in academic clinical research” for all stakeholders in Switzerland. In this Viewpoint, the authors focus on one aspect of the survey and interview results reported by Eberle and colleagues from PPI contributors, researchers, academic research infrastructure staff, and representatives of regulatory and funding bodies to identify a possible direction for a basic PPI framework in Switzerland. Specifically, they describe how they prepare two groups of stakeholders – clinical researchers and PPI contributors – for collaboration. They present clear definitional distinctions to help clinical researchers prepare for the 2025 call for proposals from the Swiss National Science Foundation (SNSF) for Investigator-Initiated Clinical Trials (IICT) and provide important background information that is essential for understanding the fundamentals of PPI.A call for universal access to science: how the Swiss Medical Weekly aims to contribute
No abstract available.
Metabolic risk after living kidney donation: an analysis of the Swiss Organ Living-Donor Health Registry
BACKGROUND: Due to persistent organ shortage, the selection criteria for living kidney donors have broadened to include elderly donors and those with co-morbidities. As little is known about metabolic health after living kidney donation, this prospective, multicentre cohort study explored metabolic changes among living kidney donors, with a particular focus on weight trajectories.
METHODS: We analysed metabolic and cardiovascular parameters before and after living kidney donation in 466 consecutive living kidney donors recorded in the Swiss Organ Living-Donor Health Registry between January 2018 and August 2022. Outcomes included weight, blood pressure, haemoglobin A1c (HbA1c) levels, and the occurrence of new-onset type 2 diabetes mellitus, arterial hypertension and cardiovascular diseases. Donors were stratified by predonation body mass index (BMI) and by postdonation weight change.
RESULTS: Obese donors (BMI ≥30 kg/m²) more frequently had pre-existing hypertension at baseline than non-obese donors (31.6% vs 18.3%, p = 0.03). During follow-up (median 2.9 years), 6% of living kidney donors developed arterial hypertension, 2.6% developed cardiovascular diseases and 1.1% developed type 2 diabetes mellitus. Obese donors had a higher incidence of postdonation type 2 diabetes mellitus than non-obese donors (p = 0.01). Changes in BMI postdonation were not correlated with age or predonation BMI. Donors with postdonation weight gain had slightly higher follow-up blood pressure, but no clear differences in rates of new-onset hypertension or type 2 diabetes mellitus were observed between weight-change groups.
CONCLUSIONS: This exploratory analysis suggests that living kidney donation is generally metabolically safe. While metabolic changes were modest overall, obesity at the time of donation was associated with a slightly higher frequency of postdonation type 2 diabetes mellitus, underscoring the importance of counselling on lifestyle modification before donation.
Characteristics of severely injured trauma patients transported by helicopter emergency medical services in Switzerland: a retrospective cohort study
BACKGROUND: Information on severely injured patients transported by helicopter emergency medical services (HEMS) in Switzerland is scarce. This study, with a special focus on sex differences, aimed to gain insights into the demographics, injury characteristics and outcomes of these patients and to provide data that could help improve prehospital trauma care.
METHODS: This is a retrospective multicentre cohort study analysing data collected by the Swiss Trauma Registry. Patients aged 16 or older, who were admitted by helicopter emergency medical services to a level 1 trauma centre in Switzerland between 2018 and 2022, with an Injury Severity Score (ISS) of ≥16, were included.
RESULTS: Overall, 2714 trauma patients were analysed in the present study. The majority of these patients were male (73.7%). Blunt trauma was the main cause of injury (93.6%), with traffic accidents (43.5%) and falls (43.3%) being the most common accident mechanisms. A greater percentage of male patients than female patients were involved in motorcycle crashes (16.5% vs 6.9%, p <0.001). Female patients were more frequently involved in accidents as pedestrians (6% vs 2.7%, p <0.001) and experienced more falls below 3 metres of height (22.9% vs 14.7%, p <0.001). The median ISS of our cohort was 24 (interquartile range [IQR]: 19–30). The most common injuries were thoracic trauma (67%), head trauma (66.7%) and spine trauma (50.3%). Men suffered more thoracic injuries (68.9% vs 61.9%, p = 0.001) and their median Abbreviated Injury Score (AIS) Thorax was significantly higher (3.0 [IQR: 0–3] vs 2.0 [IQR: 0–3], p <0.001). Women had a higher prevalence of pelvic fractures (29.3% vs 21.5%, p <0.001) and suffered more fractures of long bones in their upper extremities (22.2% vs 15.7%, p <0.001). There was no significant difference in in-hospital mortality between women and men (15.7% vs 14.6%, p = 0.493), nor in other outcome parameters.
CONCLUSION: To our knowledge, this is the first analysis of data on severely injured trauma patients transported by helicopter emergency medical services in Switzerland. While there were notable differences between women and men in terms of accident mechanisms and injury characteristics, no significant differences in outcome parameters were observed.
Successful targeting of the alternative complement cascade with iptacopan for the treatment of IgA nephropathy: a case report
INTRODUCTION: Currently, approved disease-specific therapies for patients with immunoglobulin (Ig) A nephropathy in Switzerland are scarce. According to the 2024 KDIGO guidelines, current treatments focus on reducing proteinuria and nephron loss using nephroprotective regimens consisting of renin-angiotensin system blockade, the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and the dual endothelin angiotensin receptor antagonist sparsentan. Systemic glucocorticoids and a targeted-release formulation of budesonide are other therapeutic options to reduce IgA nephropathy-specific drivers of nephron loss. However, their use has been associated with adverse effects, even with targeted-release budesonide, and the benefit of these therapies remains to be weighed against the risk of treatment-emergent toxicity. This highlights the ongoing need to identify more effective and safer therapies for the treatment of IgA nephropathy. In the last few years, increasing understanding of the pathogenetic role of alternative complement pathway dysregulation in the onset and progression of IgA nephropathy has led to the development of new complement-targeting therapies. Iptacopan is an oral inhibitor of complement factor B that effectively blocks the alternative complement pathway.
CASE PRESENTATION: We report the successful treatment of a 40-year-old female patient suffering from IgA nephropathy with iptacopan. In this patient, despite maximum tolerated renin-angiotensin system blockade and fully dosed SGLT-2 inhibitor administration, we failed to achieve the desired reduction in proteinuria to <0.5 g/day. Proteinuria persisted at a level of >1 g/day despite the goal of blood pressure ≤120/70 mm Hg being achieved. Impressively, within just two months after the initiation of iptacopan, we noted a reduction in proteinuria to 0.5 g/day, and after nearly six months, we reached our goal, with proteinuria at <0.3 g/day, a value continuing to the present day. Further, the medication was well-tolerated.
CONCLUSION: To the best of our knowledge, our case report is the first in Switzerland to show that selective inhibition of the alternative complement pathway in IgA nephropathy results in significant and ongoing reduction of proteinuria after six months of therapy, supporting the innovative concept of targeting the alternative complement pathway with iptacopan to treat IgA nephropathy.
The impact of the COVID-19 pandemic on cancer incidence, stage distribution and survival in Switzerland: a register-based cohort study
BACKGROUND: The COVID-19 pandemic disrupted healthcare systems worldwide. This raised concerns about delays in cancer diagnosis and treatment, with potentially worse patient outcomes. The aim of this nationwide, population-based cohort study was to investigate the impact of the COVID-19 pandemic on cancer incidence, stage distribution and one-year survival in Switzerland.
METHODS: We used national cancer registry data for the period 2017–2021 from the National Agency for Cancer Registration in Switzerland, covering all except three cantons. We estimated national cancer incidence counts and calculated age-standardised incidence rates for all cancers and separately for female breast cancer, colorectal cancer, lung cancer, melanoma and prostate cancer. We calculated proportional stage distributions for cancer types and estimated observed and relative one-year survival for all cancers and cancer types based on Swiss population life tables. Results were analysed descriptively.
RESULTS: We included 218,736 cancer cases diagnosed between 2017 and 2021. Annual incidence counts of all cancer cases increased in 2020 (2.1%) and 2021 (7.3%) compared to the mean of 2017–2019. When evaluating monthly incidence counts, we observed a substantial decrease during the COVID-19 lockdown period, which was largest in April 2020 (−19.9% for all cancers). This decrease was most pronounced for female breast cancer (−39.9%), followed by prostate cancer (−29.0%), colorectal cancer (−28.7%) and melanoma (−26.9%). An increase in incidence counts for all cancers was observed in March 2021 (18.8%). We observed no clear shift in stage distributions across 2017–2021. The observed and relative one-year survival for all cancers and individual cancer types was similar in 2020 and slightly higher in 2021 compared to 2017–2019.
CONCLUSIONS: This nationwide study suggests that the pandemic had no major effect on short-term cancer patient outcomes. These findings are of importance for policymakers and the public health system regarding future pandemics.
Bleeding risk after native and transplant kidney biopsy – a single-centre observational study
STUDY AIM: Renal biopsies provide important and decisive information for diagnosis and therapy. Although biopsies are considered safe, bleeding complications remain a concern. We analysed the complication rate after kidney biopsies in native and transplant kidneys and their association with platelet function analyser bleeding time (PFA BT) and estimated glomerular filtration rate (eGFR).
METHODS: This single-centre observational study included all patients who underwent an ultrasound-guided kidney biopsy at the University Hospital Basel from 2015 to August 2019. The main objective was to investigate the association of PFA BT with significant bleeding complications in kidney biopsies. Significant bleeding was defined as a haemoglobin decrease of >10 g/l within 48 hours or the need for transfusion after bleeding, according to the discretion of the treating physician. The pre-biopsy assessment included bleeding time using PFA BT, INR, thrombocyte count, and eGFR.
RESULTS: A total of 819 kidney biopsies—285 native and 534 transplant—were analysed. Complications occurred in 32 biopsies (3.9%): 18 (6.3%) in native and 14 (2.6%) in transplant kidneys. Bleeding was the most frequent complication in both groups. Overall, low eGFR (p = 0.01) and prolonged PFA BT (p = 0.02) were associated with bleeding complications. In native kidney biopsies, inpatient biopsy was associated with bleeding complications (p = 0.005), while in transplant kidney biopsies, bleeding complications were associated with time after transplantation (p <0.001), prolonged PFA BT (p <0.001), and diagnostic biopsies (p = 0.01). In the multivariable model, low eGFR was the only significant factor associated with bleeding complications (odds ratio 3.57, 95% confidence interval 1.76-7.23, p <0.001).
CONCLUSIONS: A low eGFR, especially below 30 ml/min, is associated with increased bleeding risk in native and transplant kidney biopsies.
From gaps to compliance: a 12-year retrospective cohort study of trends in mismatch repair protein testing and Lynch syndrome identification in colorectal cancer in Central Switzerland
STUDY AIM: Alongside an analysis of incidence trends in colorectal cancer and Lynch syndrome over time, the study sought to evaluate the implementation and trends of reflex testing for mismatch repair proteins and key mutations in relevant genes (BRAF, KRAS, NRAS) in colorectal cancer in Central Switzerland from 2011 to 2022, specifically assessing adherence to the Swiss Academy for Quality in Medicine (SAQM) guidelines, in order to identify any gaps or inconsistencies in testing practices that may hinder the diagnosis of Lynch syndrome or microsatellite instability, highlighting areas requiring improvements for optimal patient care.
METHODS: This retrospective study enrolled 2602 patients with 2673 histologically confirmed colorectal cancers. Data collection from the Central Switzerland Cancer Registry included demographic, molecular and immunohistochemical profiles of all histologically confirmed colorectal cancers over the analysed 12-year period. Statistical analyses were performed using R (v4.3.1) with the tidyverse package. Normality was assessed with the Shapiro-Wilk test and non-parametric comparisons were made using the Wilcoxon rank-sum test. Chi-square and Fisher’s exact tests were used for categorical variables, while Poisson and binomial regression models were used to evaluate temporal trends.
RESULTS: Of 2673 tumours analysed, 76% were tested for mismatch repair proteins, with testing rates improving significantly from 58% in 2011 to >99% in 2022. Among these, 14% showed a mismatch repair protein deficiency, with 77% being MLH1-related and 23% non-MLH1-related, categorising them as Lynch-suspected. 73% (n = 257) of the MLH1-deficient tumours underwent further molecular testing for BRAF mutations. Among these, 33% showed no mutation, also categorising them as Lynch-suspected, while the remaining 67% were categorised as sporadic. In total, 6% of the tested tumours were categorised as Lynch-suspected and required further testing and/or genetic counselling. Statistical estimates suggest that among the non-tested tumours, 88 cases could potentially harbour a microsatellite instability, including approximately 5 Lynch-suspected cases. Additionally, in 44 cases, incorrect mismatch repair proteins were tested, potentially leading to missed microsatellite instability. Among the 59 tumours that did not undergo BRAF testing, approximately 20 may have been Lynch-suspected and missed due to insufficient testing. Tumour incidence and the proportion of Lynch-suspected tumours among all tumours remained stable over time, without cantonal hotspots.
CONCLUSIONS: Remarkable progress in colorectal cancer diagnostics across Central Switzerland could be demonstrated, leading to a near-complete compliance with guidelines for mismatch repair proteins and molecular testing by 2022. This high adherence to guidelines provides a solid foundation for better personalised surveillance and treatment, ultimately improving the quality of care for colorectal cancer patients in the region. However, during the early years of the study some gaps existed, particularly in testing practices for rectal cancers and incomplete molecular follow-up, potentially missing some patients with a microsatellite instability, who could have benefited from different therapies, and Lynch syndrome patients, who together with their families could have benefited from tighter surveillance.
Advancements in less-invasive aortic root, ascending aorta and arch surgery: current evidence and future directions
Aortic surgery is one of the most challenging areas in cardiovascular medicine because of the complexity of the procedure and the potential for life-threatening complications. Historically, median sternotomy has been the gold-standard approach for thoracic aortic interventions, providing excellent exposure to the entire ascending aorta and the distal aortic arch. This approach has yielded satisfactory postoperative results over the years. However, the invasiveness of median sternotomy is associated with significant surgical trauma, increased postoperative pain and prolonged recovery. Minimally invasive aortic surgery has emerged as a potential alternative to conventional approaches with the aim of combining the benefits of minimally invasive cardiac surgery with the demands of complex aortic interventions. In this review, we aimed to critically analyse the current experiences with minimally invasive aortic surgery via partial upper sternotomy for the treatment of aortic root, ascending aorta and aortic arch pathologies. The partial upper sternotomy (PUS), as a less invasive approach in minimally invasive aortic surgery, represents a substantial advancement in the field of aortic surgery. The current literature on minimally invasive aortic surgery via PUS is predominantly based on retrospective, single-centre studies with small sample sizes, which limits the strength of the conclusions and generalisability. Ventilation time, intensive care unit (ICU) stay, length of hospital stay and bleeding complications can be reduced using this approach. Survival was not negatively affected and cosmetic results were improved by minimally invasive aortic surgery.
Caffeine, nicotine, cannabis, and psilocybin: Pharmacology, toxicology, and potential therapeutic uses of four naturally occurring psychoactive substances
Psychoactive substances are compounds that can influence perception, consciousness, cognition, and emotions. The psychoactive substances caffeine, nicotine, cannabis, and psilocybin all originate from natural sources and can be used without complex processing or synthesis. Their natural availability has contributed to a long-standing history of human use and cultural significance. Caffeine and nicotine are freely available and commonly used as everyday stimulants, whereas psilocybin is more strictly regulated and cannabis has been legalised in some countries and regions. Some of these substances have been intensively studied, and their pharmacological and toxicological properties are well known, but ongoing research continues to investigate their therapeutic use for specific diseases and disorders. This narrative review aims to provide an overview of the pharmacology and toxicology of these four naturally occurring psychoactive substances, including a summary of the currently available evidence on their therapeutic potential, health benefits, and associated risks.
Equitable health care in the context of migration
The health policy guiding principle of equitable access to healthcare faces barriers in the context of migration, on the part of both those affected and the health system. The operationalised measurement of health inequity, the training and sensitisation of healthcare professionals regarding needs-based care, diversity, transcultural and socio-medical aspects, and ensuring high-quality communication are among the measures that can contribute to reducing inequitable care (e.g. underuse) in this population.
Long-term impacts of Legionnaires’ disease on health and wellbeing: rationale, study design and baseline findings of a matched cohort study (LongLEGIO)
BACKGROUND AND STUDY AIMS: Is there a post-acute infection syndrome for Legionnaires’ disease? Legionnaires’ disease is a form of primarily community-acquired pneumonia caused by Legionella spp. bacteria. Legionnaires’ disease and other forms of bacterial community-acquired pneumonia may lead to persistent health and wellbeing impairments. It remains unclear whether these are caused by the community-acquired pneumonia-causing pathogen or the pneumonia itself. We present the rationale and design of a matched cohort study to investigate the persistent health impacts of Legionnaires’ disease and compare them with persistent manifestations of other bacterial (Legionella test-negative) community-acquired pneumonia. We also present baseline characteristics of the study cohorts.
METHODS: Legionnaires’ disease patients and Legionella test-negative community-acquired pneumonia patients with confirmed or clinically suspected bacterial aetiology were recruited from university and cantonal/regional hospitals and matched for sex, age, hospital type and date of diagnosis. Questionnaire-based interviews are conducted at baseline and 2, 6 and 12 months after the start of appropriate antibiotics. The questionnaires focus on patient-reported outcome measures and cover long-term symptoms, use of health services and health-related quality of life.
RESULTS: Between June 2023 and June 2024, 59 patients with Legionnaires’ disease (59.3% male, median age 69 years [interquartile range [IQR]: 57–80]) and 60 patients with other bacterial (Legionella test-negative) community-acquired pneumonia (63.3% male, median age 69 years [IQR: 60–79]) were enrolled. Admission to the intensive care unit was required for 13.6 % of Legionnaires’ disease patients and 8.3 % of other bacterial community-acquired pneumonia patients. Chronic kidney failure was more prevalent among Legionnaires’ disease patients (15.3% vs 10.0%), while chronic obstructive pulmonary disease (20.0% vs 11.9%), malignancies (33.3% vs 13.6%) and an immunocompromised status (25.0% vs 13.6%) were more common in Legionella test-negative community-acquired pneumonia patients. Furthermore, Legionella test-negative community-acquired pneumonia patients reported lower baseline quality of life scores than Legionnaires’ disease patients. Differences in pneumonia severity, comorbidities and self-reported quality of life scores will be accounted for in future analyses.
CONCLUSIONS: The LongLEGIO study will contribute to research on post-acute infection syndromes and provide the data for a more holistic assessment of the disease burden of Legionnaires’ disease.
Evolution of adult respiratory syncytial virus detection: impact of testing strategy changes and pandemic-related measures at a Swiss regional hospital, 2016–2023
BACKGROUND AND AIMS: Respiratory syncytial virus (RSV) is increasingly recognised as an important cause of respiratory illness in adults. We aimed to analyse clinical and epidemiological characteristics of patients with a positive reverse transcription–polymerase chain reaction (RT-PCR) test in a Swiss regional hospital between 2016 and 2023, including predisposing factors, patient demographics, treatment approaches and clinical outcomes. We also examined temporal patterns of RSV detection during periods of changes in testing strategies and public health measures.
METHODS: In this retrospective cohort study at Spital Emmental, we analysed all consecutive in- and outpatients with respiratory symptoms who underwent nasopharyngeal RT-PCR testing following local syndrome-based testing protocols between December 2016 and February 2023. The testing methodology changed from trivalent (influenza A/B, RSV) to quadrivalent (SARS-CoV-2, influenza A/B, RSV) RT-PCR in March 2022, with simultaneous expansion of the testing criteria. Temporal patterns and incidence of positive RSV tests relating to periods of national COVID-19-related public health measures (13 March 2020 and 17 February 2022) were assessed.
RESULTS: Of 8135 RT-PCR tests performed, 231 (2.8%) were positive for RSV. The mean age was 69 years, with complete clinical data available for 194 patients. Of these, 157 (81%) required hospitalisation, of whom 19 (12%) were classified as nosocomial infections. Of the hospitalised patients, 14 (9%) required intensive care, with an in-hospital mortality rate of 6%. Major comorbidities in inpatients included cardiac disease (54%), pulmonary disease (49%) and anaemia (43%). Testing patterns showed marked temporal variation: 1766 tests (22%) were performed pre-pandemic, 125 (1%) during pandemic measures and 6244 (77%) after pandemic restrictions were lifted. The introduction of quadrivalent testing in March 2022 led to an increase in testing volume, but lower positivity rates (6% pre- vs 2% post-implementation).
CONCLUSIONS: Our results demonstrate RSV-associated resource use and mortality in adults. The temporal evolution of RSV detection in our cohort paralleled changes in testing practices, highlighting the complex interplay between diagnostic strategies and observed disease patterns in a regional hospital setting. Recently introduced preventive vaccination strategies may help to address the impact on patients and healthcare resource utilisation.