Continuing Education Activity

Acute cystitis is a urinary bladder infection, constituting the most frequent manifestation of urinary tract infection (UTI) in women. UTIs rank among the most prevalent infectious diseases globally, affecting approximately 150 million individuals annually and accounting for substantial morbidity and healthcare expenditure. In the U.S., the estimated economic burden of recurrent UTIs exceeds $5 billion per year, with more than 1 million emergency department visits attributed to these infections.

The condition typically arises from ascending infection by uropathogens, most commonly Escherichia coli, facilitated by risk factors such as female sex, sexual activity, pregnancy, urinary stasis, and postmenopausal changes. Bacterial adherence to the uroepithelium initiates an inflammatory response resulting in dysuria, urinary frequency, urgency, and suprapubic discomfort.

Diagnosis is based on urinalysis and urine culture findings. Management involves antimicrobial therapy guided by local resistance patterns and symptom relief measures. Untreated or recurrent infections may lead to pyelonephritis or chronic bladder dysfunction, although the overall prognosis remains favorable with appropriate therapy.

This activity for healthcare professionals is designed to enhance learners' competence in evaluating and managing acute cystitis. Participants will advance their mastery of the condition's etiology, risk factors, pathophysiology, clinical presentation, and evidence-based diagnostic and therapeutic approaches. Improved skills will equip clinicians to collaborate with interprofessional teams caring for affected individuals.

Objectives:

• Identify the constellation of signs, symptoms, and laboratory findings that support the diagnosis of acute cystitis, with attention to patient-specific predisposing factors.
• Implement personalized, evidence-based approaches for managing acute cystitis and avoiding potential sequelae.
• Improve patient awareness of causes, warning signs, proper management, and preventive measures to reduce the recurrence of acute cystitis.
• Collaborate with members of the interprofessional team, including family physicians, internists, urologists, obstetricians/gynecologists, and infectious disease specialists, to deliver efficient, comprehensive, and coordinated care for individuals with acute cystitis.

Introduction

Acute cystitis is an infection of the urinary bladder that represents the most common urinary tract infection (UTI) in women. Acute uncomplicated cystitis is defined as a UTI confined to the lower urinary tract without systemic manifestations in healthy, premenopausal, nonpregnant women.[1] The majority of UTIs are uncomplicated. Women are disproportionately affected due to the anatomical proximity of the urethral meatus to the rectum and a shorter urethral length.

Typical clinical features include urinary frequency, urgency, dysuria, and suprapubic discomfort. Diagnosis is established through patient history, physical examination, urinalysis, and urine culture. Management should be individualized, generally conducted on an outpatient basis, and guided by local antimicrobial resistance patterns.

Etiology

In both community and hospital settings, members of the Enterobacteriaceae family predominate in UTIs, with uropathogenic Escherichia coli (UPEC) being the principal pathogen.[2] E. coli, a gram-negative bacterium, accounts for 80% to 90% of acute cystitis cases.[3] The remaining infections are caused by Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter species, and gram-positive organisms, including Streptococcus species, Enterococcus species, and Staphylococcus saprophyticus.[4][5]

The primary risk factor for acute cystitis in female individuals is the anatomical proximity of the urethral meatus to the anus, facilitating contamination of the vulvar and periurethral region with rectal bacteria. A short urethral length further increases susceptibility by providing easier access to the bladder. Untreated infections may ascend to the kidneys, causing pyelonephritis, and, in severe cases, bacteremia.

Sexual activity introduces bacteria into the bladder, increasing infection risk. Additional factors include diaphragm or spermicide use, new or multiple sexual partners, and onset of the 1st UTI before age 15 years.[6] Postmenopausal women experience an increased risk due to low estrogen states.[7]

Individuals with structural urinary tract anomalies, indwelling catheters, neurogenic bladder, polycystic kidney disease, renal calculi, obesity, diabetes mellitus, immunocompromised status, or prior drug-resistant UTIs are considered high-risk. These patients are more likely to develop complicated UTIs.

Epidemiology

UTIs are among the most prevalent infectious diseases globally, affecting approximately 150 million individuals annually and resulting in significant morbidity and healthcare costs. The estimated economic burden of recurrent UTIs in the U.S. exceeds $5 billion per year, with more than 1 million emergency department visits for UTI occurring annually.[8]

Acute cystitis is the most common bacterial infection in female patients. In the U.S., an estimated 11% of women report at least 1 physician-diagnosed UTI each year, with a 60% lifetime probability of experiencing a UTI.[9][10][11] Approximately 25% to 50% of patients diagnosed with a UTI will have at least 1 additional UTI within a year, and 3% to 5% will experience multiple recurrences.

UTI exhibits marked sex disparity, with premenopausal women 20 to 40 times more likely than men of the same age to develop infection.[12] In men, the annual incidence is approximately 3%, with a lifetime prevalence of 20%. Factors contributing to lower incidence in men include a longer urethra and a urethral meatus located farther from the rectum.[13] Clinical manifestations in this group are similar to those in women.

The risk of UTI increases with age in both sexes. Lower UTIs in men typically manifest after 60 years of age, often associated with prostate syndrome.[14] Historically, all UTIs in men were classified as complicated. However, infections in male persons aged 15 to 50 years without risk factors, such as bladder outlet obstruction, urological anatomical abnormalities, immunocompromised status, comorbidities (including renal failure, uncontrolled diabetes, or renal transplant), or urolithiasis, may be considered uncomplicated and managed accordingly.[15]

Uncomplicated UTIs in men should be suspected in otherwise healthy individuals presenting with classic symptoms such as acute dysuria, urinary frequency, urgency, and nocturia. The diagnosis is supported by the absence of systemic manifestations or complicating factors, including anatomical abnormalities, urethral strictures, benign prostatic hyperplasia, urinary retention, or urolithiasis.[16]

Pathophysiology

UTIs result from the migration of bacteria from the periurethral region, frequently originating from the gastrointestinal tract, into the urethra and urinary bladder.[17] Uropathogens, including Escherichia coli, adhere to and invade the bladder epithelium via specific adhesins, precipitating cystitis. Untreated infections may ascend to the kidneys, causing pyelonephritis, and in severe cases, may progress to bacteremia and sepsis.

History and Physical

Patient history is the most critical tool for diagnosing acute uncomplicated cystitis and should be corroborated by a focused physical examination and microscopic urinalysis. History should encompass symptom onset, severity, duration, flank pain, fever, chills, vaginal discharge, and other systemic manifestations, such as malaise, nausea, vomiting, or generalized weakness.. A comprehensive assessment of prior sexually transmitted infections is also recommended. Common clinical features of cystitis include urinary frequency, dysuria, urgency, suprapubic discomfort, cloudy urine, and hematuria.

UTIs may be classified as uncomplicated, complicated, or asymptomatic bacteriuria. Clinical manifestations are generally similar in uncomplicated and complicated cystitis. Acute uncomplicated cystitis is defined as a UTI confined to the lower urinary tract without systemic signs or symptoms in a healthy, premenopausal, nonpregnant woman.

Complicated cystitis refers to a UTI confined to the bladder but associated with a higher risk of treatment failure due to host factors, including male sex, pregnancy, older age, an indwelling catheter, and immunocompromised status. Additional risk factors include relevant functional or structural anatomical abnormalities of the urinary tract. Predisposing conditions that increase susceptibility to infection, such as diabetes mellitus or chronic kidney disease, also classify a UTI as complicated.

Asymptomatic bacteriuria is defined as a urine specimen yielding isolation of a single organism in quantitative counts of greater than 100,000 colony-forming units (CFUs) in the absence of symptoms specifically attributable to a UTI.[18] The presence of a strong odor or cloudy urine alone is insufficient to establish a diagnosis of UTI or justify antibiotic therapy. The probability of cystitis exceeds 90% in women presenting with dysuria and urinary frequency in the absence of vaginal discharge or irritation.[19]

Recurrent UTIs are defined as 2 or more culture-confirmed UTIs within 6 months or 3 or more UTIs within a year. Recurrent infections may represent a relapse, caused by the same uropathogen, or a recurrence, caused by a new uropathogen. Relapse occurs when UTI symptoms develop within 2 weeks of completing appropriate antibiotic therapy. Recurrence is defined by the development of a subsequent UTI beyond the initial 2-week period or isolation of a different uropathogen.

In pyelonephritis, patients present with symptoms similar to cystitis, accompanied by flank pain and costovertebral angle tenderness. Systemic manifestations may include fever, chills, nausea, and vomiting.[20] 

Postmenopausal women experience estrogen deficiency, leading to vulvovaginal atrophy, reduced vaginal secretions, and decreased lactic acid production by vaginal lactobacilli, increasing susceptibility to infection. Clinical manifestations include urinary frequency, urgency, nocturia, stress urinary incontinence, and UTIs. Additional contributing factors, such as pelvic organ prolapse and urinary incontinence, promote bacterial proliferation and infection through urinary retention, stasis, and incomplete bladder emptying.[21][22]

Prostatitis is diagnosed in men presenting with rectal, pelvic, or suprapubic pain, often accompanied by a tender prostate on digital rectal examination. Diagnosis is confirmed by a positive 2- or 4-glass urine test result.[23] Acute bacterial prostatitis is uncommon and is associated with systemic manifestations, including fever and chills.[24] Urethritis is suspected in patients exhibiting purulent urethral discharge or reporting multiple new sexual partners.[25][26]

In pregnant women, clinical manifestations are similar to those observed in nonpregnant women. However, asymptomatic bacteriuria represents a significant risk factor for the development of UTI during pregnancy. If untreated, pregnant patients are at increased risk of developing both acute cystitis and pyelonephritis. The incidence of acute cystitis in pregnancy is approximately 1% to 2%, comparable to that in nonpregnant women.[27] In older adults, both women and men often present with atypical manifestations, including altered mental status (new-onset confusion), functional decline, fatigue, or falls.[28]

Individuals who have indwelling urinary catheters or perform intermittent self-catheterization are at increased risk of bacterial colonization and UTIs.[29][30] Catheter-associated UTIs (CAUTIs) account for 70% to 80% of cases, as indwelling devices provide a conduit for opportunistic organisms to enter the urinary tract at the catheter-collecting tube junction or drainage bag port. Ascending organisms can damage the uroepithelial mucosa, resulting in symptomatic infection.

Physical Examination

Physical examination is typically unremarkable in acute uncomplicated cystitis, although 10% to 20% of women may demonstrate suprapubic tenderness. Acute pyelonephritis should be suspected in patients who appear systemically ill, particularly in the presence of fever, tachycardia, flank pain, or costovertebral angle tenderness. Pelvic examination is indicated in cases of suspected pelvic organ prolapse or recurrent UTIs. Postvoid residual urine measurement and digital rectal examination should be performed in all men presenting with a UTI.

Self-Diagnosis

Women with a history of treated acute uncomplicated cystitis are generally accurate and reliable in recognizing recurrent episodes. Prompt recognition allows for early evaluation and initiation of appropriate management, reducing the risk of complications.

Evaluation

The urine specimen for UTI testing should be collected to minimize contamination from skin, vaginal debris, or extraneous bacteria. This collection is typically achieved using a midstream clean-catch method or an in-and-out straight catheterized sample. 

Urine Dipstick Analysis

The convenience and cost-effectiveness of urine dipstick testing make it a common diagnostic tool. This modality is an appropriate alternative to urinalysis and urine microscopy for diagnosing acute uncomplicated cystitis. A urine dipstick assesses specific gravity, pH, protein, leukocyte esterase, nitrites, blood, ketones, glucose, bilirubin, and urobilinogen. Leukocyte esterase and nitrites usually yield a positive result, and urine pH tends to be higher (alkaline) in the setting of a UTI.

Dipstick urinalysis does not evaluate for the presence of squamous epithelial cells or bacteria. Nitrite and leukocyte esterase are the most accurate indicators of acute uncomplicated cystitis in symptomatic women. Two meta-analyses indicate that a positive nitrite result on dipstick testing is useful for diagnosing a UTI, whereas negative results for both leukocytes and nitrites can reliably exclude infection.

Microscopic Urinalysis

A complete urinalysis includes physical, chemical, and microscopic examination of the urine sample. A midstream clean-catch or catheterized sample is preferred to minimize potential contamination. Most studies indicate that leukocyte esterase and leukocytes lack specificity and may yield false-positive results, whereas nitrites are more specific, producing fewer false-positive findings, but lack sensitivity and may lead to false-negative outcomes.

Nitrites on a urinary dipstick are the most reliable nonmicroscopic indicator of UTI. Gram-negative bacteria typically reduce nitrate to nitrite in the urine, a process requiring approximately 6 hours. Urine contains no nitrites under normal conditions, rendering the test relatively reliable. False-positive results may arise from prolonged dipstick exposure to air prior to testing, expired dipsticks, medications causing reddish urine discoloration (eg, phenazopyridine), or a urine sample older than 4 hours. False-negative findings may occur with nonnitrite-producing organisms, a low-nitrate diet, overly concentrated urine, or low urinary pH.[31][32]

Leukocyte esterase detects the presence of intact or degraded neutrophils on a urinary dipstick. False-positive results may occur due to contamination from vaginal or foreskin secretions, expired or improperly stored dipsticks, or discolored urine from foods or medications (eg, nitrofurantoin). False-negative yields may be observed in cases of early infections, excess intake of vitamin C, overly concentrated urine, ketonuria, or proteinuria.[33] Overall, leukocyte esterase serves as a useful indicator but is less reliable than nitrites.

Pyuria is defined as greater than 10 white blood cells per high-power field. Pyuria detected by urinalysis demonstrates high sensitivity (95%) but lower specificity (71%). Accuracy depends on the quality of urine collection, the promptness of examination, and the laboratory technician's expertise, as yeast may occasionally be misidentified as white blood cells.[34]

Bacteriuria is typically defined as a colony count greater than 100,000 CFU/mL of a single organism from a clean-catch urine sample. Several studies have demonstrated that a significant proportion of symptomatic women present with colony counts below 100,000 CFU/mL and suggest that greater than 100 CFU/mL in a symptomatic woman should be considered consistent with infection.

The presence of pyuria, bacteriuria, or even culture growth exceeding 100,000 CFU/mL does not alone establish a UTI diagnosis unless accompanied by urinary or systemic symptoms, such as dysuria, urgency, frequency, bladder spasms, pain, fever, or hematuria.[35][36][37] This distinction is particularly relevant in patients with chronic indwelling catheters. Bacteriuria does not constitute a UTI in the absence of symptoms.

Urine Culture

Urine culture is considered the gold standard for diagnosing a UTI. This test is not always required in uncomplicated cystitis but is strongly recommended for bacterial identification and antibiotic selection in cases of treatment failure, suspected resistance, or persistent symptoms. Absolute indications for urine culture include complicated UTIs, pyelonephritis, pregnancy, and recent antimicrobial therapy. Cultures assist in distinguishing relapsing from recurring infections and in selecting appropriate antibiotics, including dosage and duration. Urine cultures typically yield colony counts of 100,000 CFU/mL in patients with UTIs, but lower counts do not exclude infection.

Urine cultures require up to 18 hours for bacterial growth using standard laboratory techniques. Samples should be sent immediately to the laboratory or refrigerated to prevent accelerated bacterial proliferation if left at room temperature.

Although urine cultures do not typically affect management in the emergency department, they are critical in follow-up when patients fail to respond to initial therapy. Therefore, a urine culture should be obtained whenever treating a patient for a UTI. Routine posttreatment urinalysis or urine culture is unnecessary in asymptomatic patients with uncomplicated cystitis.

Imaging

Imaging is generally unnecessary in routine cases of uncomplicated cystitis. In complicated cases, ultrasound may be used to evaluate for hydronephrosis or abscess formation. Computed tomography provides superior assessment for kidney stones, hydronephrosis, emphysematous changes, pyelonephritis, and abscesses. Patients presenting with acute pyelonephritis cannot be reliably distinguished from those with obstructive pyonephrosis—a surgical emergency—without imaging. Therefore, either ultrasound or computed tomography is recommended.

Cystoscopy

Cystoscopy is not indicated and provides no added benefit in routine cases of cystitis. Evaluation with this modality should be considered only when structural or pathological abnormalities are suspected.

Treatment / Management

Several key elements should be considered when treating cystitis. Antibiotic selection should be individualized, as no single agent provides universal efficacy for acute uncomplicated cystitis. Selection should account for cost, local antibiotic resistance patterns, the severity of clinical presentation, the risk of adverse effects, and patient-specific factors, including allergy history and prior urine culture results. Increasing antimicrobial resistance has rendered treatment more challenging and complex.

Clinical improvement typically occurs within 48 to 72 hours of therapy initiation. Although 3-day courses can achieve excellent cure rates, longer treatment durations are frequently recommended.

Uncomplicated Cystitis 

First-line antibiotic therapy for acute uncomplicated cystitis includes nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), and fosfomycin. Nitrofurantoin, administered at 100 mg orally twice daily for 5 to 7 days, is generally preferred, accounting for approximately 32% of prescriptions. The drug's limited tissue penetration precludes use in systemic or kidney infections.[38] TMP-SMX, 160/800 mg orally twice daily for 3 to 5 days, should be used only if local resistance rates are below 20%.[39] Fosfomycin is administered as a single 3-gram oral dose.[40]

Second-line options include β-lactams such as amoxicillin, cephalosporins, and fluoroquinolones. Fluoroquinolones are not recommended as 1st-line therapy due to increasing bacterial resistance. Intravesical gentamicin solution (80 mg in 50 mL normal saline) may be considered in selected cases.[41][42]  Phenazopyridine, a bladder analgesic, can serve as adjunctive therapy to alleviate dysuria symptoms.[43]

Complicated Cystitis 

Consensus on a single treatment approach has not been reached. However, therapy generally requires a longer duration, typically 7 to 14 days, for complicated UTIs and UTIs in men. Prophylactic antibiotics, including cephalosporins, TMP-SMX, nitrofurantoin, and, occasionally, fluoroquinolones, may be indicated for patients with complicated or recurrent cystitis.

Foley catheters 

Indwelling Foley catheters should be replaced prior to urine culture to eliminate biofilm and reduce the risk of contamination. Biofilms can develop on catheters within a few days. Therefore, urine cultures are ideally obtained from newly placed catheters. CAUTIs are defined as infections occurring in individuals who currently have a urinary catheter or have had a catheter in place within the preceding 48 hours. Management of CAUTIs follows the same principles as treatment in patients without catheters.

Pregnant women 

Physiological, hormonal, and functional changes during pregnancy necessitate careful antibiotic selection, preferably with U.S. Food and Drug Administration category B agents such as penicillins, oral cephalosporins, and fosfomycin. Both asymptomatic bacteriuria and acute cystitis require treatment, and a urine culture should always be obtained. Antibiotic therapy may be adjusted based on culture results. However, initiation of treatment should not be delayed while awaiting laboratory confirmation.

Antibiotic safety is critical in pregnancy. The most commonly prescribed agents are β-lactams, including cephalosporins, as well as nitrofurantoin and fosfomycin. Fluoroquinolones are contraindicated.[44][45] Nitrofurantoin should be avoided at term and during labor and delivery, while TMP-SMX is not recommended during the 1st trimester or at term.

Men 

Acute cystitis in men is generally classified as a complicated infection. Recommended antibiotics include cephalosporins, TMP-SMX, nitrofurantoin, and fluoroquinolones. Extended treatment durations are often necessary to prevent progression to chronic bacterial prostatitis.

Differential Diagnosis

A broad range of genitourinary and systemic conditions can mimic the symptoms of acute cystitis, including the ones below. Careful assessment improves diagnostic accuracy and informs targeted therapy.

• Atrophic vaginitis
• Benign prostatic hyperplasia
• Bladder cancer
• Bladder calculi
• Candidiasis
• Carcinoma in situ of the bladder
• Cervicitis
• Chlamydial infections
• Chronic pelvic pain syndrome in men
• Distal ureteral calculi
• Epididymitis
• Gonorrhea
• Interstitial cystitis
• Overactive bladder
• Pelvic inflammatory disease
• Prostatitis
• Radiation cystitis
• Sexually transmitted infections
• Syphilis
• Urethral stricture
• Urethritis
• Urinary retention
• Vulvovaginitis

Recognition of conditions that mimic acute cystitis is essential to prevent inappropriate therapy. Combining clinical assessment with selective investigations supports evidence-based decision-making.

Prognosis

Symptoms typically resolve within approximately 3 days of initiating antibiotic therapy. Spontaneous resolution occurs in roughly 20% of women with uncomplicated UTIs. Recurrent cystitis develops in approximately 25% to 50% of women within 6 months of the initial infection. Overall, uncomplicated UTIs carry an excellent prognosis in women without significant risk factors.

Complications

Complications of acute cystitis encompass a range of renal, infectious, and systemic outcomes, including acute renal failure, development of antibiotic-resistant organisms, emphysematous pyelonephritis, focal nephronia, obstructive pyonephrosis, persistent urinary tract symptoms, prostatitis, pyelonephritis, recurring or relapsing UTIs, renal or perinephric abscess, renal vein thrombosis, and sepsis. In pregnant women, complications also include pyelonephritis, preterm labor, and low birth weight.

Deterrence and Patient Education

Patient education is essential to prevent recurrent UTIs. Prevention strategies may be classified as behavioral, nonantimicrobial, and antimicrobial. Behavioral measures include increased hydration, typically 2 to 3 L of water daily, and pelvic floor physical therapy, both of which have been shown to reduce the incidence of UTIs. Nonantimicrobial strategies encompass the use of vaginal estrogen, cranberry products, methenamine, and D-mannose. Antimicrobial prophylaxis may be indicated in women with frequent infections. Postcoital prophylaxis is recommended when sexual activity precipitates UTIs, while low-dose continuous antibiotic prophylaxis may be considered for patients with recurrent infections.

Perineal and personal hygiene also contribute to prevention. Recommended measures include avoiding baths, cleaning the vaginal area first in the shower to reduce contamination, using adult or baby wipes rather than toilet paper for perineal cleansing, employing a fresh washcloth with gentle soap, voiding shortly after sexual activity, and handwashing prior to wiping after urination. These interventions collectively reduce bacterial exposure and the risk of recurrent infection.

Pearls and Other Issues

Although antibiotic therapy for symptomatic and recurrent UTIs provides clear clinical benefits, overuse and inappropriate selection have contributed to a global rise in antimicrobial resistance, posing an increasing public health threat. Nonantimicrobial strategies should be considered, and therapy should be individualized according to local resistance patterns and urine culture results.

Hospital admission may be warranted in patients with acute cystitis or pyelonephritis who exhibit severe, complicated, or high-risk clinical features. Prompt recognition of these indications, outlined below, allows for timely intervention, appropriate monitoring, and escalation of care when necessary.

• Complications, such as sepsis, shock, acute kidney injury, abscess formation, and emphysematous changes
• Failure of outpatient therapy
• High-risk conditions, including immunocompromised status, renal transplant, and anatomic or functional urinary tract obstruction
• History of nonadherence to treatment
• Inability to perform self-care due to encephalopathy, dementia, or significant weakness
• Intractable nausea or vomiting
• Persistent pain
• Obstructive pyelonephritis (pyonephrosis)
• Pregnancy
• Pyelonephritis with systemic manifestations

Addressing modifiable risk factors and employing evidence-based preventive interventions enhances patient outcomes. Preventive strategies should be tailored to individual risk profiles to minimize recurrence and associated complications.

Enhancing Healthcare Team Outcomes

Acute cystitis is often managed by an interprofessional team that includes a primary care provider (medical doctor, doctor of osteopathy, nurse practitioner, or physician assistant), internist, urologist, gynecologist, urogynecologist, infectious disease specialist, nephrologist, and, when pregnancy is present, obstetrician. Most uncomplicated cases resolve quickly with treatment. However, persistent symptoms may warrant hospital admission and appropriate consultations.

Nursing staff and pharmacists support the care team by providing patient counseling and performing medication reconciliation. Pharmacists may also evaluate the appropriateness and dosage of the selected antimicrobial agents. Each team member must document any changes in the patient's condition, including adverse drug reactions or therapeutic failure, and communicate findings to the team to initiate timely interventions.

Key considerations in managing cystitis include individualizing antibiotic therapy based on patient characteristics, tolerance, allergies, prior infection history, medical comorbidities, and local resistance patterns. No single antibiotic is universally optimal for acute, uncomplicated cystitis, although nitrofurantoin is the most frequently selected agent. Selection should also take into account cost, severity of presentation, risk of adverse effects, and culture results. Rising antimicrobial resistance has increased treatment complexity, and consultation with infectious disease specialists is advised in complex cases.

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Disclosure: Ruqayya Gill declares no relevant financial relationships with ineligible companies.

Disclosure: Stephen Leslie declares no relevant financial relationships with ineligible companies.

Disclosure: David Minter declares no relevant financial relationships with ineligible companies.