(a) (i) What are the different types of epidemiological studies? (ii) What are the possible sources of control in case-control…

(a)(i) Types of epidemiological studies

1. Observational studies: the investigator only observes.

• Descriptive studies: describe disease by time, place and person and generate hypotheses. Examples are case reports, case series, cross-sectional (prevalence) surveys such as NFHS, and ecological (correlational) studies.
• Analytical studies: test hypotheses. They include ecological studies, where the unit is a population; cross-sectional studies; case-control studies, which go from effect to cause and measure the odds ratio; and cohort studies, which go from cause to effect and measure incidence, relative risk and attributable risk. Cohort studies may be prospective, retrospective (historical) or combined, for example the Framingham Heart Study.
• Hybrid designs: nested case-control, case-cohort and case-crossover studies.

2. Experimental (intervention) studies: the investigator assigns the exposure.

• Randomised controlled trials: clinical and therapeutic trials, including parallel, crossover, factorial and cluster designs.
• Field trials: on healthy people at risk, for example the 1954 Salk polio vaccine field trial.
• Community trials: on whole communities, for example water fluoridation.
• Non-randomised trials: "before and after" studies with or without a control, and natural experiments.

(a)(ii) Sources of controls in case-control studies

Controls should come from the same source population as the cases, be free of the disease, and have had the same opportunity for exposure.

• Hospital controls: patients in the same hospital with unrelated conditions. They are easy to obtain and cooperative, and recall is comparable. Their diagnoses should be varied and unrelated to the exposure, to avoid Berkson's bias.
• Population (general or community) controls: drawn by random sampling from electoral rolls, the census, household surveys, population registers or random-digit dialling. They are the most representative but costly, and their response is lower.
• Neighbourhood controls: people living in the same locality or adjacent houses, which matches for socio-economic and environmental factors.
• Relatives, friends and associates: spouses, siblings, friends or workmates. They control for genetic, household or occupational factors but risk overmatching.
• Special groups: for example, the same birth cohort, the same school or the same insurance scheme.
• More than one control group, or multiple controls per case: up to about 4:1. More controls per case raise statistical power, with little gain beyond 4:1.

Matching (individual or frequency) on confounders such as age and sex is applied to whichever source is used.

(a)(iii) Advantages of case-control over cohort studies

• Suitable for rare diseases and diseases with a long latency (for example, cancers).
• Relatively quick, inexpensive and easy to carry out.
• Need comparatively few subjects.
• Several exposures or risk factors can be studied for one disease.
• No attrition (loss to follow-up) problems, and no need for long follow-up.
• No risk to subjects, and fewer ethical problems.
• Useful as the first step in an outbreak investigation, or when a hypothesis must be tested quickly.
• The odds ratio closely estimates relative risk when the disease is rare.

(b) Antenatal care

Definition. WHO (2016) defines antenatal care as the care provided by skilled health professionals to pregnant women and adolescent girls to ensure the best health conditions for both mother and baby during pregnancy. It includes risk identification, prevention and management of pregnancy-related or concurrent disease, and health education and promotion.

Objectives

• Promote, protect and maintain the health of the mother during pregnancy.
• Detect "high-risk" cases early and give them special attention. These include anaemia, hypertension or preeclampsia, GDM, malpresentation, previous caesarean, Rh-negative mothers, HIV and syphilis.
• Foresee complications and prevent them, through Td, IFA, calcium, deworming and screening.
• Remove the anxiety and dread associated with delivery, and prepare for birth and complications (birth preparedness).
• Reduce maternal and perinatal morbidity and mortality, and ensure a healthy baby.
• Teach the mother about nutrition, personal hygiene, breastfeeding, newborn care and immunisation.
• Counsel on family planning and link the mother to entitlements (JSY, JSSK, PMMVY).

Schedule of antenatal visits

• India (MoHFW): a minimum of 4 ANC visits, including registration: the 1st within 12 weeks, the 2nd at 14–26 weeks, the 3rd at 28–34 weeks and the 4th at 36 weeks to term.
• Additional care in India: the Pradhan Mantri Surakshit Matritva Abhiyan (PMSMA) gives a fixed-day specialist check-up on the 9th of every month in the 2nd and 3rd trimesters. Extended PMSMA adds visits for high-risk women.
• WHO 2016 model: at least 8 contacts, at up to 12, 20, 26, 30, 34, 36, 38 and 40 weeks.
• Traditional ideal schedule: monthly up to 28 weeks, fortnightly from 28–36 weeks, and weekly thereafter.
• Services at each visit: weight, BP, Hb, urine albumin and sugar, and abdominal examination. Blood group and Rh, HIV, syphilis and GDM screening (75 g OGTT) are done at registration and at 24–28 weeks. Other services are USG; two doses of Td (or a booster); IFA for 180 days and calcium; albendazole after the first trimester; and the Mother and Child Protection card.

Domiciliary midwifery service

This is delivery at home conducted by a trained midwife (ANM or skilled birth attendant) with a back-up referral link.

Advantages

• The mother delivers in familiar surroundings among family members, which gives psychological comfort.
• The risk of hospital (cross) infection is lower.
• Care is personal and individual, and the family can take part.
• It is less expensive for the family, with no travel.
• It relieves the burden on hospital beds.
• The mother can keep an eye on her home and children.
• It builds the midwife's rapport with the community, helping later MCH and family-planning work.

Disadvantages

• Emergencies are hard to manage, including PPH, eclampsia, obstructed labour, cord prolapse and birth asphyxia. Blood, operative facilities and neonatal resuscitation are unavailable, and referral may be delayed.
• The home may be unhygienic, overcrowded or poorly lit, making asepsis difficult.
• The mother may not get enough rest and may resume household work early.
• Supervision of the midwife is difficult, and the quality of care is variable.
• The approach does not suit high-risk or primigravid women.

India's policy now promotes institutional delivery through JSY and JSSK. Home delivery is acceptable only when attended by a skilled birth attendant, supported by ASHA-led home-based newborn care (HBNC).

(c)(i) Causes of haematuria in a 60-year-old male

Painless gross haematuria at this age is taken as urological malignancy until proven otherwise.

• Kidney: renal cell carcinoma, upper-tract urothelial carcinoma, calculi, pyelonephritis, renal tuberculosis, polycystic kidney disease, papillary necrosis (analgesics, diabetes), glomerulonephritis (IgA nephropathy, vasculitis), renal infarction or AV malformation, and trauma.
• Ureter: calculus and urothelial tumour.
• Bladder: urothelial carcinoma (the most important cause), cystitis, bladder calculus, radiation or cyclophosphamide cystitis, schistosomiasis and tuberculosis.
• Prostate: benign prostatic hyperplasia (congested vessels), carcinoma prostate and prostatitis, and bleeding after TURP or biopsy.
• Urethra: trauma, catheterisation, stricture, urethritis and carcinoma.
• Systemic and haematological causes: anticoagulant or antiplatelet therapy (these unmask underlying pathology, so evaluation is still needed), coagulopathy, thrombocytopenia, sickle-cell disease and severe hypertension.
• Other causes: exercise-induced haematuria and loin-pain haematuria.
• Pseudo-haematuria (not true haematuria): haemoglobinuria, myoglobinuria, and discoloured urine from beetroot, rifampicin or phenazopyridine.

(c)(ii) Management of carcinoma prostate in a 60-year-old male

1. Diagnosis and staging

• DRE and serum PSA.
• Multiparametric MRI before biopsy (PI-RADS scoring).
• Targeted plus systematic biopsy, preferably transperineal because of the lower sepsis risk, with Gleason score and ISUP grade group.
• Staging by bone scan and CT, or PSMA PET-CT, for TNM stage.
• Risk grouping (NCCN/EAU): low risk is PSA under 10, ISUP grade group 1 and T1–T2a; intermediate risk is PSA 10–20, grade group 2–3 or T2b–c; high risk is PSA over 20, grade group 4–5, or T3 or above.
• Life expectancy and comorbidity: a fit 60-year-old usually has over 15 years ahead, so curative treatment is preferred.

2. Localised disease

• Low risk: active surveillance with PSA every 6 months, DRE, repeat MRI and biopsy, and definitive treatment on progression. Radical treatment is an alternative.
• Intermediate risk: radical prostatectomy (open, laparoscopic or robot-assisted) with pelvic lymph node dissection when indicated. An alternative is external-beam radiotherapy (IMRT/IGRT) or brachytherapy, with short-term ADT (4–6 months) for unfavourable disease.
• High risk and locally advanced (T3–T4 or N1): EBRT with long-term ADT (18–36 months), with abiraterone added in very high-risk node-positive disease. Radical prostatectomy with extended lymphadenectomy is done in selected patients as part of multimodal treatment.

3. Metastatic hormone-sensitive disease

• Androgen deprivation therapy: bilateral orchiectomy (cheap and practical in India), a GnRH agonist (leuprolide, goserelin) with an antiandrogen cover for the flare, or a GnRH antagonist (degarelix, relugolix).
• Treatment intensification: ADT is always intensified with an androgen-receptor pathway inhibitor (abiraterone with prednisolone, enzalutamide, apalutamide or darolutamide), with or without docetaxel (triplet therapy).
• Radiotherapy: to the prostate in low-volume disease.

4. Castration-resistant prostate cancer (mCRPC)

• A switch of androgen-receptor agent, docetaxel, then cabazitaxel.
• PARP inhibitors (olaparib, talazoparib) for BRCA or homologous-recombination-repair mutations.
• ¹⁷⁷Lu-PSMA-617 radioligand therapy, or radium-223 for symptomatic bone-only disease.

5. Supportive care and follow-up

• Bone health: calcium, vitamin D, zoledronic acid or denosumab.
• Palliation: radiotherapy for bone pain and cord compression.
• Side effects of ADT: osteoporosis, metabolic syndrome, cardiovascular risk and hot flushes are managed.
• Rehabilitation after surgery: continence and erectile rehabilitation.
• PSA follow-up: every 3–6 months. Biochemical recurrence is PSA above 0.2 ng/mL after prostatectomy, or nadir + 2 ng/mL after radiotherapy (Phoenix), and prompts salvage radiotherapy.