Dear Editor,
Cardiovascular disorders (CVDs) are the major cause of mortality worldwide(1). Developing nations account for more than 80% of total CVD mortality. CVD continues to be the major somatic cause of productivity loss, resulting in exceptionally high death and disability rates(2). Age is one of the main risk factors for CVDs, thus this is a major worry, particularly in an aging population.(1)
This study (BMJ 2024;385:e078523) provides a good understanding of cardiovascular disease (CVD) incidence and highlights critical areas that needs public health attention. One of the major strengths of this study is that it analyzes CVD incidence by age, sex, socioeconomic status, and region. The concentration of CVD diagnoses at the end of life, with a median age of 65 to 80 years, highlights the need for focused therapies in older populations. However, the notable incidence of venous thromboembolism in individuals under 45 underscores the importance of vigilance and prevention efforts across all age groups. The study's focus on socioeconomic inequality and their significant relationship with CVD incidence is particularly compelling. The rise in non-atherosclerotic heart disease incidence and the decline in atherosclerotic disease incidence point to a possible change in the CVD landscape that calls for new approaches to prevention and treatment. The use of diagnostic codes for diagnosis of disease is highly commendable.
I would like to mention some of the limitation of this study as well. This study provides a deep insight in the trends of multiple cardiovascular diseases over 20 years (from 1 Jan, 2000 to 30 June,2019) but don’t provide information about the latest trends, from 2019 onwards. There might be a principal change in recent trends that needs to be addressed. Moreover, the study doesn’t cover a wide range of other CVDs like Infective Heart Diseases, Mitral regurgitation, Tricuspid valve disease, Hypertrophic cardiomyopathy, Ventricular fibrillation, Long QT syndrome, etc. The study also lacks insights on the trends of congenital heart conditions such as Atrial septal defect (ASD), Ventricular septal defect (VSD), Tetralogy of Fallot, Patent ductus arteriosus (PDA), etc. Furthermore, the incidence of CVDs should be correlated with its other risk factors such as alcohol consumption, unhealthy diet, physical inactivity, stress, and family history of CVDs. A rising number of thromboembolic disorders, valve problems, and cardiac arrhythmias were observed in the study but it did not look into strategies, effective interventions, and healthcare policies to combat with them. Future researchers need to observe these rising trends and look out for effective treatment, prevention strategies and, lifestyle modifications. Higher incidence of CVDs in patients with low socioeconomic status also needs to be addressed in future researches.

1. Fukumoto Y. Lifestyle intervention for primary prevention of cardiovascular diseases. Eur J Prev Cardiol. 2022 Dec 7;29(17):2250–1.
2. Van Camp G. Cardiovascular disease prevention. Acta Clin Belg. 2014 Dec;69(6):407–11.

Dear Editor,

We appreciate the comment by Dr Bell et al. In their letter, they reflect on whether our choice of method (i.e., interval-censoring and Weibull) has influenced our point estimate for the active surveillance group after 20 years given the differences in follow-up between active surveillance and immediate LLETZ (1).

In our study cohort, most women in the active surveillance group were diagnosed with CIN2 after 2013 where active surveillance had been implemented nationally. In contrast, immediate LLETZ was the primary procedure prior to 2013. This explains the differences in median follow-up between the two groups, as mentioned by Dr Bell et al.

If we had chosen a constant rate time-to-event model, we agree with the calculations by Dr Bell et al. However, as demonstrated in the table below, 75% of the cancer cases in the immediate LLETZ group (36 out of 48), were diagnosed within 1 year after CIN2 diagnosis. In contrast, only 50% of the cancers in the active surveillance group were diagnosed within 1 year, with the other 50% diagnosed after 1 year when the risk set is smaller due to censoring. A constant rate model would poorly fit the underlying data and would therefore give biased risk estimates.

Instead, we used a Weibull model to account for non-constant hazards and used interval-censoring to account for cancers occurring between clinical visits – the frequency of which are not uniform across individuals. The Weibull model is an often-used model for carcinogenesis that allows for constant (i.e., exponential), monotonically decreasing, or monotonically increasing hazards (2). We checked for fit against the non-parametric curve, i.e., the Turnbull estimator (which is analogous to the Kaplan-Meier estimator but can be used to fit interval censored data) [Figure S2 in the Supplement]. Both the Weibull and non-parametric curves show that relative to the active surveillance group, the cancer risk curve flattens out quickly following immediate LLETZ.

Although, we found that active surveillance is associated with a nearly 4-fold higher risk of cervical cancer than immediate LLETZ, we must be careful basing our clinical decisions solely on the relative estimate. Here, we must reflect upon the absolute estimates; after 20 years around 0.8-2.6% of women with CIN2 were diagnosed with cervical cancer. Thus, the absolute risk of developing cervical cancer after CIN2 is low.

Please see full rapid response including Table 1: https://docs.google.com/document/d/1BeLKs5zIixVrkQEC6p-RrOB4UQVKUZYIfXx6...

References
1. Lycke KD, Kahlert J, Petersen LK, et al. Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study. BMJ 2023 doi: 10.1136/bmj-2023-075925
2. Kopp-Schneider A. Carcinogenesis models for risk assessment. Stat Methods Med Res 1997;6:317-40. doi: doi.org/10.1177/096228029700600403

Dear Editor

The NHS decision to implement a policy of routine administration of RSV vaccine to pregnant women from 28 weeks of pregnancy (1) is concerning.

Currently the UK is the only nation that does not offer the alternative product, nirsevimab – a monoclonal antibody that can be given by injection to newborn babies. Nirsevimab is the preferred RSV immunisation in France, Spain, Belgium, Luxembourg, Ireland, Germany, Chile and some States in Australia.

The only other country that includes RSV vaccine in its policy is the USA, where it is licensed for use only between 32 and 36 weeks because of the potential risk of preterm births.(2) In the USA nirsevimab is also recommended and is more frequently used.

Preliminary reports suggest that nirsevimab, when given to neonates, has been effective at reducing hospital admissions for bronchiolitis.(3) Long term safety has not been established.

The NHS policy is that “women should be offered RSV vaccination in each pregnancy”. This conflicts with advice from the CDC that women should not be revaccinated in subsequent pregnancies, as there is no evidence that this is safe and effective.(4)

In view of the possible preterm birth risks, it is difficult to understand why the NHS guidance should state that “The ideal opportunity to offer vaccination would be at the 28 week antenatal contact”. Although enhanced post-marketing safety surveillance is being undertaken in USA, this will not cover vaccines administered as recommended in UK, earlier than the 32nd week of pregnancy.

1) https://www.gov.uk/government/publications/respiratory-syncytial-virus-r...
2) https://www.fda.gov/media/168889/download?attachment
3) https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00215-9/abstract
4) https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-06-26-2...

Dear Editor

We thank Dr Guy Titley for his comments and regret if our paper inadvertently created the impression that infertility does not have a profound impact on men. We fully agree that infertility affects both men and women, biologically, psychologically, sociologically, and as a couple. For the most part, we avoided gender terminology in our paper, referring instead to individuals and couples. We also agree that more research on men’s infertility is needed.

That said, we do not think that it is time to stop recognizing that infertility affects many women disproportionally, especially but not only in Low-and Middle-income Countries (LMICs.) While we recognize that local differences exist in the nature and degree of this disproportion, we do not consider its existence to be an assumption but a reality based on extensive medical and social scientific literature from across the globe. Only when this evidence is replaced by new and better evidence that refutes current knowledge will the fortunate moment come to consider the impact of infertility as being gender equal. Until then, we should act on existing evidence, including, by way of example, recent evidence that at least one in three infertile women in LMICs experience current or recent intimate partner violence (1). Simultaneously, we should not discriminate against men or their experiences and psychological suffering attributable to infertility. In this manner we can hope to make progress towards a time to which Dr Guy Titley is aptly referring, but which in our view has yet to come.

Reference:
Wang Y, Fu Y, Ghazi P, Gao Q, Tian T, Kong F, Zhan S, Liu C, Bloom DE, Qiao J. Prevalence of intimate partner violence against infertile women in low-income and middle-income countries: a systematic review and meta-analysis. The Lancet Global Health. 2022 Jun 1;10(6):e820-30. DOI:https://doi.org/10.1016/S2214-109X(22)00098-5