Treatment and Management of Non-infectious Diseases

Pharmacological, Surgical, Lifestyle, Emerging

In 1897, Felix Hoffmann at Bayer AG synthesised aspirin, and it was prescribed for pain and fever for 74 years before John Vane identified in 1971 that it works by irreversibly inhibiting COX-1 and COX-2, reducing prostaglandin synthesis. Today, low-dose aspirin (75–100 mg/day) is prescribed for cardiovascular protection, a completely different indication from the original discovery, enabled only by understanding the mechanism. This spectrum from empirical use (1897) to mechanism-based dosing (post-1971) illustrates the four treatment categories: pharmacological, surgical, lifestyle modification, and emerging molecular therapies, each managing the disrupted mechanism at a different level.

The appropriate treatment depends on the disease type, its stage, the specific molecular disruption involved, and the individual patient's circumstances. In practice, most non-infectious diseases are managed with a combination of approaches rather than a single treatment.

Technology in disease management and monitoring

Health equity barriers to treatment access

Four treatment categories: pharmacological (drugs targeting specific molecular pathways), surgical (physically remove or repair diseased tissue), lifestyle management (diet, exercise, weight, also a treatment, not just prevention), and emerging gene therapy (experimental for most conditions). Most non-infectious diseases require a combination. "Evaluate" means benefits AND limitations, not a list.

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Statins, metformin, chemotherapy and targeted therapy

We just saw the four treatment categories. That raises a question: what exactly do pharmacological drugs do at the molecular level, and how do statins, metformin, chemotherapy and targeted therapy each differ in their mechanisms? This card answers it → each drug has a specific molecular target; knowing that target, not just the drug name, is what earns HSC marks.

Understanding the mechanism of a drug, not just its name, is required for HSC extended responses. Each drug works by targeting a specific molecular component of the disease pathway.

Statins: inhibit HMG-CoA reductase → liver upregulates LDL receptors → lower LDL → slower atherosclerosis. Metformin: activate AMPK → ↓gluconeogenesis + ↑GLUT4 sensitivity (lower blood glucose). Chemotherapy: cytotoxic, damages ALL rapidly dividing cells (hence hair loss, nausea, immunosuppression). Targeted therapy: blocks cancer-specific proteins (BCR-ABL in CML, HER2 in breast cancer), fewer off-target effects but only if target present.

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Coronary artery bypass graft (CABG) and tumour excision

We just saw that pharmacological drugs each target a specific molecular step. That raises a question: what happens when the artery is already physically blocked, or a tumour is solid and localised, what can a drug not do that surgery can? This card answers it → CABG and tumour excision are structural interventions; effective when localised, but surgery does not address the underlying disease mechanism.

Surgical treatments physically intervene in the disease process rather than targeting molecular mechanisms. They are generally reserved for cases where pharmacological or lifestyle management is insufficient, or where rapid intervention is required.

Coronary Artery Bypass Graft (CABG)

In advanced CVD, atherosclerotic plaques narrow or block coronary arteries, restricting blood flow to the myocardium. A CABG creates a new route for blood to bypass the blocked section by grafting a blood vessel (typically the saphenous vein from the leg, or the internal mammary artery) between the aorta and a point beyond the blockage.

Evaluation: CABG is highly effective for multi-vessel coronary artery disease where angioplasty is unsuitable. However, it is an open-heart procedure requiring general anaesthesia, carries significant surgical risk (infection, stroke, death), requires weeks of recovery, and costs approximately $30,000–$50,000 AUD. In Australia, Medicare covers most of this cost for eligible patients, making it accessible. Cardiac rehabilitation programs post-CABG significantly improve long-term outcomes.

Tumour Excision (Cancer Surgery)

Surgical removal of a primary tumour is the first-line treatment for many localised solid cancers (breast, bowel, melanoma). The goal is to remove the tumour with a clear margin of healthy tissue, ensuring no cancer cells remain at the edges (positive margins increase recurrence risk).

CABG: graft vessel (saphenous vein/internal mammary artery) bypasses blocked coronary segment → restores myocardial blood flow. CABG does NOT remove plaques, statins and lifestyle still required post-surgery. Tumour excision: remove primary tumour with clear margins; curative ONLY if localised (not metastasised). Stage I melanoma ~98% vs stage IV ~30–50% 5-year survival, early detection is critical.

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Not just prevention, lifestyle modifies disease mechanisms in already-diagnosed patients

We just saw that surgery corrects structural problems but doesn't treat the underlying disease process. That raises a question: is there an intervention that actually reverses the metabolic dysfunction driving T2D and CVD, not just managing it? This card answers it → lifestyle management (diet, exercise, weight loss) is first-line treatment, not just prevention, and can achieve T2D remission by restoring insulin sensitivity.

Lifestyle management is often presented as prevention, but for patients already diagnosed with Type 2 diabetes or CVD, it is also a primary treatment intervention, and in early-stage T2D, it can be sufficient to achieve remission without pharmacological treatment.

Type 2 Diabetes, Lifestyle as First-Line Treatment

In early-stage T2D (as in Marcus's case from Think First), the Australian Diabetes Society guidelines recommend lifestyle intervention as first-line treatment:

• Dietary modification: Reducing refined carbohydrate intake lowers post-meal blood glucose spikes. Reducing saturated fat decreases visceral fat, which drives insulin resistance. Increasing dietary fibre slows glucose absorption.
• Physical activity: Aerobic exercise increases GLUT4 transporter translocation to muscle cell membranes independently of insulin signalling, muscle cells can take up glucose without requiring insulin to function. This directly lowers blood glucose. Resistance training also increases muscle mass, expanding the body's glucose sink capacity.
• Weight reduction: Loss of 5–10% body weight significantly reduces visceral fat, which produces adipokines and free fatty acids that impair insulin receptor signalling. Substantial weight loss (>15%) can achieve sustained T2D remission in some patients.

CVD, Cardiac Rehabilitation

After a myocardial infarction (heart attack) or CABG, cardiac rehabilitation programs combine supervised exercise, dietary counselling, and psychological support. Structured cardiac rehabilitation reduces 30-day readmission rates by ~25% and significantly improves long-term survival. Lifestyle management post-CABG is essential because the surgery addresses the blockage but not the underlying atherosclerotic disease process.

Lifestyle is treatment (not just prevention) for already-diagnosed T2D/CVD. Diet (↓refined carbs, ↓saturated fat, ↑fibre); exercise (GLUT4 translocation → insulin-independent glucose uptake); weight loss 5–10% → ↓insulin resistance; >15% → T2D remission possible. Cardiac rehabilitation post-MI/CABG reduces readmission by ~25% and improves long-term survival.

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The PBS, Medicare, and equity in treatment access

We just saw that lifestyle modification is a primary treatment for T2D and CVD. That raises a question: how do we compare all treatments, not just biologically, but in terms of cost and whether patients can actually access them? This card answers it → evaluate using effectiveness + cost + accessibility; the PBS and Medicare reduce financial barriers but geographic and socioeconomic gaps remain.

The HSC syllabus requires you to evaluate the effectiveness, cost, and accessibility of treatments for at least two non-infectious diseases. "Evaluate" means providing a balanced judgement, acknowledging strengths and limitations, not simply listing features.

The Role of PBS and Medicare in Australia

The Pharmaceutical Benefits Scheme (PBS) subsidises approved medicines, meaning patients pay a co-payment (currently ~$7.70 for concession holders, ~$31.60 general, as of 2024) rather than the full market price. Without PBS listing, imatinib would cost ~$40,000 per year, placing it beyond reach for most Australians. Medicare covers hospital care including CABG surgery and specialist consultations, substantially reducing the financial barrier to surgical intervention.

However, accessibility is not purely financial. Geographic barriers (rural and remote Australians have reduced access to specialist surgeons and cardiac rehabilitation programs), health literacy, and socioeconomic determinants of health create inequality in treatment uptake even when treatments are theoretically subsidised.

Evaluate treatments using effectiveness, cost, and accessibility. PBS subsidises medicines (imatinib $40,000/yr → ~$40/month on PBS); Medicare covers hospital care including CABG. Accessibility is not only financial, geographic barriers, health literacy, and socioeconomic factors limit access even when treatments are subsidised. Rural Australians face reduced access to specialists and cardiac rehabilitation.

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Overview only, full analysis in L17

We just saw that conventional treatments manage consequences of molecular defects. That raises a question: is there a way to actually fix the genetic mutation itself, treating the disease at its source rather than managing its downstream effects? This card answers it → gene therapy (replacement via viral vector; CRISPR genome editing) targets disease at DNA level, but remains experimental for most conditions.

Gene therapy aims to treat disease at its genetic cause, rather than managing its downstream consequences. Two main approaches are relevant to non-infectious disease:

• Gene replacement: A functional copy of a mutated gene is delivered into target cells using a viral vector (typically an adeno-associated virus, AAV). Example: trials delivering functional CFTR gene copies to lung epithelial cells in cystic fibrosis patients. The vector carries the gene into the cell nucleus where it is expressed, producing functional CFTR protein.
• Genome editing (CRISPR-Cas9): The Cas9 endonuclease is guided to a specific DNA sequence by a guide RNA, where it makes a precise cut. The cell's repair machinery then inserts a corrected sequence. This has been used experimentally to correct BRCA1 mutations in cell cultures and has entered clinical trials for some cancers and genetic blood disorders (sickle cell disease, beta-thalassaemia).

The key limitation of gene therapy is delivery, getting the functional gene or editing machinery to the correct cells in sufficient quantities without triggering an immune response. Immune reactions to viral vectors have caused serious adverse events in early trials. Off-target genome editing effects are also a safety concern for CRISPR-based approaches.

Gene replacement: deliver functional gene copy via viral vector (AAV) → expressed in target cells (e.g. CFTR for CF). CRISPR-Cas9: guide RNA directs Cas9 to cut DNA at specific site → repair machinery inserts corrected sequence. Still EXPERIMENTAL for most non-infectious diseases, always qualify in exam answers. Key limitation = delivery (immune reactions to viral vectors; off-target editing effects).

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