Dysmenorrhoea

Definition

Primary Dysmenorrhoea

Pathophysiology

1. In the late luteal phase, progesterone levels fall
2. This triggers enzymatic lysis, releasing phospholipids and generating arachidonic acid
3. The cyclooxygenase (COX) pathway is activated, producing prostaglandins (especially PGF2α and PGE2) and thromboxane
4. Women with dysmenorrhoea have upregulated COX enzyme activity and prostanoid synthase activity
5. Elevated prostanoids cause:
   • Increased uterine contractions with a dysrhythmic pattern
   • Increased uterine basal tone and active pressure
   • Decreased uterine blood flow (ischaemia)
   • Peripheral nerve hypersensitivity

Symptoms

• Begins a few hours before or just after the onset of menstruation
• Lasts 48-72 hours
• Is colicky/cramping in nature, centred in the suprapubic area
• Resembles labour pain
• May radiate to the lumbosacral back and anterior thighs

Signs

• Vital signs are normal
• Suprapubic tenderness on palpation
• Bimanual exam may reveal uterine tenderness, but:
  • No cervical motion tenderness
  • No adnexal tenderness or masses
  • Pelvic organs are otherwise normal

Diagnosis

• Rule out underlying pelvic pathology through history and physical exam
• Check for abnormal uterine bleeding, dyspareunia, or non-midline focal pain (which point to secondary causes)
• NAAT for gonorrhoea/chlamydia; CBC and ESR if endometritis/PID is suspected
• Pelvic ultrasound if symptoms don't resolve with NSAIDs
• Laparoscopy is not required to establish the diagnosis

Secondary Dysmenorrhoea

• Endometriosis (classically associated with dyspareunia, dyschezia, lower back pain, and infertility)
• Adenomyosis
• Uterine fibroids (leiomyomas)
• Endometrial polyps
• Pelvic inflammatory disease (PID)
• Cervical stenosis
• Copper IUD

Risk Factors for Dysmenorrhoea

• Heavy menstrual loss
• Premenstrual symptoms
• Age younger than 30 years
• History of PID
• Early menarche

Management

Primary Dysmenorrhoea

• Ibuprofen, naproxen, ketoprofen, mefenamic acid, and nimesulide are all superior to placebo
• Should be started 1-3 days before menses onset (or at first onset of minimal pain/bleeding) and continued every 6-8 hours for the first few days of flow
• A 4-6 month trial is recommended; if one NSAID class fails, try another
• Contraindicated in GI ulcers or aspirin hypersensitivity
• Provide >80% sustained response rates

• Combined oestrogen-progestin OCP, progestin-only pills, transdermal patch, vaginal ring, injectable progestin, or levonorgestrel-releasing IUD
• Mechanism: inhibit ovulation, decrease endometrial proliferation, reduce prostaglandin levels
• Can be used as first-line in patients who also desire contraception
• Continuous or extended-cycle regimens are as effective as cyclic regimens

• Omega-3 fatty acids (fish oil, krill oil) - shown to reduce dysmenorrhoea, likely through competing with omega-6 derived prostaglandins
• Vitamin B1 (thiamine) at 100 mg/day - one large RCT supports efficacy
• Magnesium - promising but optimal dose unclear
• Local heat application, exercise, yoga, acupuncture

Secondary Dysmenorrhoea

• Endometriosis: first-line is combined OCP ± NSAIDs; second-line is high-dose progestins or GnRH analogues; surgical resection by laparoscopy if medical therapy fails
• Adenomyosis: combined hormonal treatment, LNG-IUD, or hysterectomy after childbearing is complete
• Fibroids: medical (NSAIDs, hormonal therapy, GnRH analogues) or surgical (myomectomy, ablation, hysterectomy)

Global Prevalence

Infective Endocarditis (IE) - Clinical Notes

Definition

Classification

Epidemiology

• Incidence: approximately 3-14 cases per 100,000 persons/year in developed countries
• In the United States: an estimated 10,000-20,000 new cases per year
• Accounts for approximately 1 case per 1,000 hospital admissions
• A 2025 systematic review of 133 studies (PMID: 40015544) characterised its global epidemiological profile and mortality trends
• S. aureus has become the most common cause of IE in most industrialised countries, displacing viridans streptococci, driven largely by healthcare contact and IV drug use

Pathogenesis

1. Endothelial damage - from turbulent blood flow (valve abnormalities), instrumentation, or jet lesions
2. Sterile vegetation formation - platelets, fibrin, and coagulation molecules aggregate to form a Nonbacterial Thrombotic Endocarditis (NBTE) nidus
3. Transient bacteraemia - bacteria seed the sterile vegetation (from dental procedures, gut/skin flora, IV drug use, IV lines)
4. Microbial proliferation - bacteria grow within the vegetation, reaching 10⁹-10¹¹ CFU/g of tissue. The avascular surface of valves impedes antibiotic penetration and healing
5. Metastatic infection - emboli seed high-flow organs (kidneys, spleen, brain); mycotic aneurysms may form from arterial wall infection

Predisposing Conditions

• Mitral valve prolapse (especially with regurgitation) - now the leading pre-existing risk factor
• Degenerative valvular disease
• Injection drug use
• Congenital heart disease (especially uncorrected VSD)
• Previous endocarditis
• Prosthetic cardiac valve (accounts for 10-20% of all IE)

• Rheumatic heart disease (still important in developing countries)
• Bicuspid aortic valve
• Idiopathic hypertrophic subaortic stenosis
• Coarctation of the aorta

• IV catheters, hyperalimentation lines, pacemakers, cardiovascular implantable electronic devices
• Haemodialysis access
• Comorbidities: diabetes mellitus, HIV infection, end-stage renal disease, neutropenia, malignancy, alcohol use

Microbiology

• HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) - oral commensals, slow-growing
• Streptococcus gallolyticus (formerly S. bovis) - strongly associated with colorectal adenocarcinoma; warrants colonoscopy
• Fungi (Candida, Aspergillus) - prosthetic valves, immunocompromised
• Culture-negative IE (~10% of cases) - prior antibiotics, HACEK, Coxiella burnetii (Q fever), Bartonella, Brucella, Tropheryma whipplei

Clinical Features

Symptoms

• Fever - most consistent sign (may be absent in elderly subacute cases)
• Fatigue, malaise, weight loss (non-specific constitutional symptoms)
• Night sweats, chills
• Myalgia/arthralgia (~50% of patients)
• Symptoms of heart failure
• Neurological symptoms (stroke/TIA in up to 15-20% of patients)

Signs - Cardiac

• New or changing murmur - present in 90% of patients with left-sided lesions; its absence is common in healthcare-associated IE
• Signs of heart failure (raised JVP, pulmonary oedema) - an ominous sign
• Splenomegaly - more common in subacute disease

Peripheral Stigmata (embolic/immunological)

Petechiae - small hemorrhagic spots (embolic)

Osler node - painful fingertip nodule (immunological)

Morphology (Pathology)

• Vegetations: friable, bulky masses on valve leaflets (usually on the low-pressure side - atrial surface of AV valves; ventricular surface of semilunar valves)
• Most common valves: Mitral and aortic (left-sided)
• Tricuspid valve is the target in IV drug users (right-sided IE)
• Vegetations may erode into the myocardium → ring abscess (perivalvular abscess)
• Shedding of emboli → septic infarcts in brain, kidneys, spleen
• Bacterial infection of arterial wall at embolisation sites → mycotic aneurysms

Diagnosis

Blood Cultures

• Obtain at least 3 sets from separate venipuncture sites (aerobic + anaerobic bottle each)
• Collected at least 1 hour apart to document continuous bacteraemia
• Starting antibiotics before cultures reduces sensitivity by ~one third - culture first if possible
• Bacteraemia in IE is continuous (unlike the intermittent bacteraemia of other infections)

Echocardiography

• Indicated in virtually all patients with suspected or known IE
• TTE (transthoracic) - first-line, but limited sensitivity for small vegetations and prosthetic valves
• TEE (transoesophageal) - preferred when:
  • TTE is of poor quality or negative despite high suspicion
  • Prosthetic valve is involved
  • S. aureus bacteraemia (high risk)
  • Suspected perivalvular abscess
  • Elderly patients with valvular abnormalities

Modified Duke Criteria

1. Positive blood cultures - typical organism from ≥2 separate cultures (viridans streptococci, S. gallolyticus, HACEK, S. aureus, or community-acquired Enterococcus without primary focus) OR persistent bacteraemia with any organism (2 positive cultures >12 h apart, or ≥3 of 4 cultures positive >1 h apart)
2. Evidence of endocardial involvement - echocardiographic: vegetation, abscess, or new partial prosthetic valve dehiscence; OR new valvular regurgitation
3. Positive serology for Coxiella burnetii (anti-phase 1 IgG ≥1:800)

1. Predisposing condition (IV drug use or predisposing cardiac condition)
2. Fever ≥38°C
3. Vascular phenomena (arterial embolism, septic pulmonary emboli, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages, Janeway lesions)
4. Immunological phenomena (glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor)
5. Echocardiogram consistent with IE but not meeting major criteria
6. Microbiological evidence not meeting major criteria

• Definite IE: Pathologically proven OR 2 major OR 1 major + 3 minor OR 5 minor criteria
• Possible IE: 1 major + 1 minor OR 3 minor criteria
• Rejected: Firm alternative diagnosis; resolution with ≤4 days antibiotics; no pathological evidence at surgery/autopsy

Complications

Treatment

General Principles

• All IE patients should be managed in hospital with an endocarditis team (infectious disease + cardiology + cardiac surgery)
• Prolonged IV antibiotics (bactericidal, not bacteriostatic) - typically 4-6 weeks
• The avascular valve surface requires high serum drug concentrations to achieve adequate tissue penetration

Empirical/Targeted Antibiotic Therapy

• A 2025 systematic review (PMID: 39290168) found that oral step-down therapy may be a feasible alternative to full-course IV therapy for S. aureus bacteraemia/endocarditis in selected patients
• Blood cultures should be repeated 48-72 h after starting antibiotics to confirm clearance

Indications for Surgery (Early/Emergency)

1. Heart failure due to valvular dysfunction (most common indication)
2. Uncontrolled infection - perivalvular abscess, fistula, or enlarging vegetation despite antibiotics
3. Prevention of embolism - large (>10 mm) mobile vegetations, especially on the mitral valve
4. Fungal or highly resistant organism endocarditis
5. Prosthetic valve endocarditis with dehiscence or persistent bacteraemia

Prophylaxis

• Prosthetic cardiac valve or material (including TAVI, annuloplasty rings)
• Previous IE
• Unrepaired cyanotic congenital heart disease
• Repaired CHD with residual defects at or near the prosthetic material
• Left ventricular assist devices / implantable hearts
• Cardiac transplant recipients with valvulopathy

Prognosis

• Left untreated, IE is generally fatal
• With antibiotics ± surgery: mortality is significantly reduced but remains high (~15-30% in-hospital mortality)
• Adverse prognostic factors: S. aureus infection, heart failure, neurological events, perivalvular abscess, prosthetic valve involvement, healthcare-associated acquisition
• Complications (glomerulonephritis, arrhythmias, systemic embolisation) worsen prognosis