What’s in the web for family physicians − Quaternary prevention for primary care practice

Sio-pan Chan 陳少斌，Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩

According to the Wonca International Dictionary for General/Family Practice, Quaternary Prevention (QP) is defined as “Action taken to identify patients at risk of overmedicalisation, to protect them from unnecessary medical interventions, and to suggest ethically acceptable alternatives.” The concept of quaternary prevention was initially proposed by Marc Jamoulle in 1999. With the rapid advancement of medical technology such as newer imaging techniques, gene sequencing, molecular diagnostics and treatment modalities, a new definition for QP was proposed by Brodersen et al as:

“Action taken to protect individuals (persons/ patients) from medical interventions that are likely to cause more harm than good”. This new definition extends QP to include the domains of primary, secondary, and tertiary prevention. The goal is to reduce overmedicalisation (overdiagnosis and overtreatment) and iatrogenic harm.

Overdiagnosis simply means “identifying problems that are not there”. Overdiagnosis occurs when individuals are diagnosed with a condition that would never have caused them harm if left undetected and untreated. This can happen due to various factors, including:

1. Increased screening: while beneficial for early detection, widespread screening can lead to the identification of harmless abnormalities that would not have caused any symptoms or complications. A notable example is the use of PSA for screening of prostate cancer in the elderly.
2. Technological advancements: sophisticated imaging techniques and sensitive diagnostic tests can detect minute irregularities, often leading to further investigations and interventions that may not be necessary. Examples are whole body MRI scan with incidental findings or tumour marker screening with minor abnormalities.
3. Expansion on disease definitions: Broadening the definition of diseases can inadvertently categorise individuals as “sick” even if they are asymptomatic and unlikely to experience any adverse effects. Examples are Attention-Deficit/hyperactivity disorder (ADHD) particularly in children.

Overtreatment is a direct consequence of overdiagnosis ,involving unnecessary medical interventions that offer no benefit and may even cause harm. This can manifest as unnecessary surgeries and procedures. Performing invasive procedures on individuals with harmless conditions exposes them to surgical risks and complications without any real benefit. A well-known example is percutaneous coronary intervention (PCI) for mild stenosis. Another example is the use of hormone replacement therapy, which not only fails to reduce cardiovascular mortality but also increases the risk of breast cancer, stroke, and thromboembolic events. Prescribing unnecessary medications can lead to side effects, drug interactions, and contribute to antibiotic resistance. Overtreatment can also result in psychological distress and financial burden; receiving a diagnosis and undergoing unnecessary treatments can cause anxiety, fear, and financial strain on individuals and the public healthcare system. Quaternary prevention can help to reduce healthcare costs for both the public and patients. This is particularly important as medical expenses have been skyrocketing with the rapid advancement of more sophisticated investigations and treatment modalities.

Family physicians can take several steps to reduce the risk of overdiagnosis and overtreatment:

1. Evidence-Based Guidelines: Adhere to evidencebased clinical guidelines and protocols to ensure that diagnostic tests and treatments are only recommended when there is a clear benefit to the patient.
2. Shared Decision-Making: Engage in shared decision-making with patients, ensuring they are fully informed about the risks and benefits of different diagnostic and treatment options. This includes discussing the potential for overdiagnosis and overtreatment.
3. Regular Training and Education: Provide ongoing education and training for healthcare professionals on the latest research and best practices to avoid unnecessary interventions.
4. Use of Watchful Waiting: In cases where immediate intervention is not necessary, consider a watchful waiting approach, monitoring the patient's condition over time before deciding on more invasive treatments.
5. Second Opinions: Encourage patients to seek second opinions, especially for major diagnoses or treatments, to confirm the necessity and appropriateness of the proposed intervention.
6. Appropriate Use of Screening Tests: Limit the use of screening tests to populations and situations where there is strong evidence that the benefits outweigh the harms. Avoid routine screening in low-risk populations.
7. Patient Education: Educate patients about the potential harms of overdiagnosis and overtreatment, empowering them to ask questions and make informed decisions about their care.

We found that QP covers a vast spectrum of topics and involves many fields of specialties. We have separated this article into 2 parts in order to cover more areas that are relevant to family practice. In part 1, we shall first discuss about QP on the following topics;

1. Statin Overuse
2. Percutaneous Coronary Intervention (PCI)
3. Imaging-based Screening, PET, PET-CT, MRI
4. Use of probiotics

Statin Overuse:

1. Statins are overprescribed for primary prevention, study suggests. BMJ. 2018;363:k5110. doi:10.1136/ bmj.k5110.
2. Comparison of American and European Guidelines for Primary Prevention of Cardiovascular Disease: JACC Guideline Comparison. J Am Coll Cardiol. 2022. doi:10.1016/j.jacc.2022.02.001.
3. The maximum dose of atorvastatin and simvastatin as well as rosuvastatin should be restricted in East Asians. Hong Kong Med J. 2024;30:184. doi:10.12809/hkmj2311348.

In 2024, the American Heart Association (AMA) introduced a new PREVENT calculator for CVD risk to be used for primary prevention patients only (those without atherosclerotic cardiovascular disease or heart failure). Compare with the older ASCVD Risk Calculator, the most noticeable difference is the absence of LDL-C as a risk factor in this new calculator. Instead, e-GFR and HbA1C are included as risk factors. It would look somewhat counter-intuitive as it is generally believed that LDL-C plays an important role in CVD and statins are considered as the corner stone in preventing CVD.

There are significant differences in prescription guidelines of statin between the United States (US) and Europe leading to a higher rate and higher dosage of statin use in the US. This discrepancy is primarily due to the lower threshold for initiating statin therapy and broader criteria for primary prevention in the US guidelines. The number of people eligible for statins under US guidelines, studies suggest that approximately 49% of US adults aged 40-75 would qualify for statin treatment. Under European guidelines, about 32% of adults in the same age group would be eligible. Furthermore, the ACC/AHA recommends a high potency statins at higher dosage comparing with their counterparts in Europe. One would expect the CVD deaths will be less in America. According to the US AHA statistics, the age-adjusted CVD mortality rate in the US was approximately 219.4 per 100,000 people in 2018. The corresponding European figure was around 130 per 100,000 people in 2017. It was estimated that around 19.55 million more people in the U.S. would be prescribed statins compared to Europe which has about twice the population of US. Apparently the use of statin does not seem to have much effect in preventing CVD death.

It is not uncommon to see some of our completely asymptomatic patients are given high dose of statin such as 20 mg rosuvastatin simply because their elevated LDL-C. In a recent article published in The Hong Kong Medical Journal, the author has pointed out that East Asia people are much less tolerant to statin than Caucasians and that "the maximum dose of atorvastatin and simvastatin as well as rosuvastatin should be restricted in East Asians”. Important side effects of statin include but not exclusive to myalgia, myositis, liver impairment, diabetes and cognitive impairment. Therefore, family physicians should provide information for our patients in making informed choices about their own risk/benefit ratio when initiating statin therapy, particularly for primary prevention of CVD.

Percutaneous Coronary Interventions (PCIs)

1. Preventive PCI or Medical Therapy Alone for Vulnerable Atherosclerotic Coronary Plaque (PREVENT)
https://clinicaltrials.gov/study/NCT02316886

2. Evidence for overuse of cardiovascular healthcare services in high-income countries: protocol for a systematic review and meta-analysis https://pmc.ncbi.nlm.nih.gov/articles/PMC8991042/

The PREVENT trial found that while percutaneous coronary inter vention (PCI) may bring about symptomatic relief for patients with stable coronary artery disease, it does not give a significant reduction in major adverse cardiovascular events when compared to optimal medical therapy. These findings underscore the importance of tailoring treatment strategies to individual patients, carefully weighing the benefits of symptomatic relief against the potential risks associated with invasive procedures. Insights gained from the PREVENT trial have significantly influenced clinical guidelines and practices regarding the management of stable coronary artery disease. It suggests that, in many instances, medical therapy should take precedence over invasive interventions like PCI unless there are specific indications that warrant their use. Furthermore, the PREVENT trial emphasises the necessity for a thoughtful approach to treatment strategies in this patient population, advocating for a balanced consideration of the advantages of PCI alongside the proven effectiveness of conservative management options. Ultimately, the findings encourage healthcare providers to adopt a more conservative and evidence-based approach to treating stable coronary artery disease, prioritising patient safety and optimising outcomes through well-informed medical management.

Another research utilising data from the National Cardiovascular Data Registry revealed that about 11.6% of PCIs performed for non-acute indications were classified as low-value procedures. The finding underscores concerns regarding the appropriateness of PCI in certain patient populations, particularly when clinical guidelines suggest conservative management may be more suitable.

Screening for Cancer with PET and PET/CT: Potential and Limitations

1. https://jnm.snmjournals.org/content/48/1_suppl/4S#sec-24
2. Kwok y.l. Lung cancer screening by computed tomography and incidental subcentimetre lung nodules on CT images. J Soc Physicians Hong Kong. 2024 Oct;100.

Cancer screening is a hot topic in modern medicine, sparking a lot of debates and strong emotions. When we look at the available data, opinions vary widely and are often based on limited reliable information. Even widely accepted practices, like breast cancer screening, still have controversies, such as at what age to start and the overall value of mammograms. Similarly, there is no agreement on the effectiveness of screening for lung or prostate cancer as it is currently practiced.

Decisions on cancer screening should rely on solid data rather than good intentions or assumptions. It is important to understand the principles behind screening and the ongoing debates about breast, prostate, and lung cancers. Recently, some have advocated using CT, PET, or PET/CT for whole-body screening without strong supporting evidence.

The financial, legal, and safety concerns linked to whole-body CT or PET scans are significant. Current data suggest that these screenings are not justified for the general population. These scans often result in ambiguous findings that need further evaluation, adding costs and potential overdiagnoses and overtreatments. The occasional cancers they can detect are not enough to justify population-wide screening efforts.

The real benefit of screening is early treatment, not just early detection. Effective screening should aim to reduce cancer mortality, but proving this requires large, expensive, and long-term studies that are unlikely to happen. Instead of focusing on widespread screening, medical professionals should use whole-body PET/CT for diagnosing, staging, and restaging cancer, and for monitoring treatment effects. Research should also be focused on how useful whole-body PET/CT is for high-risk patients who have completed treatment but still face a high risk of recurrence.

A recent local article reported on the use of artificial intelligence (AI) in low-dose thoracic tomography (LDCT) for decision-making in the management of incidental pulmonary nodules (IPNs). The use of AI could reshape the landscape of IPN management. Similar AI applications should be equally applicable to many other imaging techniques. It is expected that with AI or AI-assisted diagnosis, we may achieve more accurate diagnoses of incidental findings and reduce overdiagnosis and unnecessary interventions.

Probiotics

Thomas, Liji. (2019, July 12). Can Probiotics Ever Be Harmful to Human Health?. News-Medical. Retrieved on October 30, 2024 from https://www.news-medical.net/health/Can-Probiotics-Ever-Be-Harmful-to-Human-Health.aspx.

Probiotics have been widely used for a number of health conditions, such as

• Digestive disorders like infectious diarrhoea, antibiotic-associated diarrhoea and functional bowel disorders
• Allergic conditions like atopic dermatitis and hay fever
• Dental and periodontal disease

The evidence supporting the use of probiotics is limited. Most research on probiotics has focused on just two types of bacteria: Bifidobacterium and Lactobacillus. There is insufficient evidence-based knowledge regarding which types of microbes to use, the optimal dosage, or the target population for any specific medical condition. In fact, the FDA has not approved probiotics for specific health claims or as a treatment for any medical conditions due to a lack of experimental proof of their benefits. As a result, the use of probiotics is largely unregulated.

In healthy individuals, probiotics are generally considered safe, some adverse effects, such as bloating, flatulence, and diarrhoea, have been reported. Long-term safety has not been studied. However, in individuals with underlying medical conditions, particularly those who are immunocompromised, probiotics may be potentially harmful. Numerous case reports have indicated that probiotics can lead to sepsis in critically ill patients, post-operative patients, infants with serious illnesses, the elderly, and immunocompromised individuals. Other possible harmful effects of probiotics include infections, the production of harmful substances by the probiotic microorganisms, and the transfer of antibiotic resistance genes from probiotic microorganisms to other microorganisms in the digestive tract. Some probiotic products have been found to contain microorganisms other than those listed on the label, and in some instances, these contaminants may pose serious health risks.

In recent years, probiotics have been promoted as miracle solutions from diarrhoea to constipation, eczema and many autoimmune conditions, leading to a flood of such products in the market. Family physicians should caution patients about the potential risks associated with the use of long-term probiotics.