Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis.

OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity). METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise. RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at £845 (within capacity) to £13,960 (under strain) compared to an HTAmin estimate of £210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario. CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.

When considering how well treatments work versus how much they cost, the focus is usually only on the price of the medicine itself. However, other real-world costs exist. In the UK, when treating certain eye problems such as neovascular age-related macular degeneration (nAMD), there are additional expenses related to running clinics and managing treatments that often go unnoticed. To get a better understanding of these hidden costs, the study examined factors like clinic workload and the extra expenses that come with it. Ten eye doctors in the UK were consulted for their expert opinions and numerous research papers were reviewed to identify these additional costs. The study grouped different costs in a tool called the nAMD Service Non-Drug Cost Instrument (nAS). When the findings of the nAS tool were compared to the usual methods of calculating costs, it was found that the conventional approach overlooked many of the actual expenses. Busy clinics face unique challenges, such as higher operational costs associated with staffing for extended hours, emergency appointments, extended waiting times and the potential to miss optimal treatment windows. This can lead to disease progression and the onset of comorbidities, which require more complex and costly treatments. Recognizing these real costs is crucial when making decisions about treatments, especially when treatments require more frequent visits to eye clinics. This study emphasizes the importance of considering all expenses, not just the obvious ones like medication and doctor visits when determining the most effective way to manage eye conditions like nAMD in the UK.

Does climate impact inflatable penile prosthesis infection (IPP) risk? Assessment of temperature and dew point on IPP infections.

BACKGROUND: Variations in climate have been associated with a greater risk of surgical site infections, urinary tract infections, and changes in the skin microbiome; however, limited data exist on the impact of climate on inflatable penile prosthesis (IPP) infections. AIM: We sought to evaluate the impact of climate on the risk of IPP infections in a large international, multicenter cohort. METHODS: We performed a multi-institutional, retrospective study of patients undergoing IPP surgery. We then evaluated whether the month or season, during which surgery was performed, affected device infections. Implant infections were defined as infections requiring device explantation. A univariate logistic regression analysis was undertaken. OUTCOMES: Our primary outcome was implant infection. RESULTS: A total of 5289 patients with a mean age of 62.2 ± 10.8 years received IPP placement. There was a fairly even distribution of implants performed in each season. A total of 103 (1.9%) infections were recorded. There were 32 (31.1%) IPP infections in patients who underwent surgery in the summer, followed by 28 (27.2%) in the winter, 26 (25.2%) in the spring, and 17 (16.5%) in the fall. No statistically significant differences were recorded in terms of season (P = .19) and month (P = .29). The mean daily temperature (P = .43), dew point (P = .43), and humidity (P = .92) at the time of IPP placement was not associated with infection. CLINICAL IMPLICATIONS: These findings provide reassurance to prosthetic urologists that infection reduction strategies do not need to be tailored to local climate. STRENGTHS AND LIMITATIONS: Climate data were not directly recorded for each hospital, but rather based on the monthly averages in the city where the surgery was performed. CONCLUSION: The climate at time of IPP placement and time of year of surgery is not associated with IPP infection risk.

Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

BACKGROUND: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. DESIGN: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. SETTING: Eight UK NHS secondary care sites. PARTICIPANTS: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. INTERVENTIONS: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. MAIN OUTCOME MEASURES: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. RESULTS: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. LIMITATIONS: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. CONCLUSIONS: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. RECOMMENDATIONS FOR RESEARCH: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. TRIAL REGISTRATION: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex^®; Mylan NV, Canonsburg, PA, USA)] was as effective as the standard daily low-dose antibiotics. A total of 240 women from across the UK took part in the trial. They were divided equally into two groups; half of the women were given methenamine hippurate and the other half were given standard low-dose antibiotics. Both treatments were prescribed to be taken every day for 1 year. To make a fair comparison, people were put into the two groups at random using a computer program. Aspects of the trial that could be improved were identified through telephone interviews with patients and recruiting staff. Feedback from these telephone interviews helped to ensure the successful conduct of the trial. Patients were followed up for 18 months, comprising the 12 months when they were taking treatment and a 6-month follow-up phase after they had finished treatment. We found that the non-antibiotic option of methenamine hippurate was no worse than the current standard treatment of daily antibiotics in preventing urinary tract infection episodes in adult women. For both treatments, patients expressed high levels of satisfaction. One advantage of the methenamine hippurate treatment was that infecting bacteria were slightly less likely to develop resistance to antibiotics. We also evaluated health-care costs of both treatments and found that methenamine hippurate seemed worthwhile to the NHS in the short term, but there was uncertainty over longer-term costs and benefits. These results will help patients with repeated urinary tract infections to decide on treatment options, particularly if they want to avoid prolonged courses of preventative antibiotics.

Predictive Association of Pre-Operative Defect Areas in the Outer Retinal Layers With Visual Acuity in Macular Hole Surgery.

Purpose: The purpose of this study was to develop methods to model the external limiting membrane (ELM) and ellipsoid zone (EZ) within the elevated cuff surrounding a macular hole (MH) to determine if the predicted size of the defect in these layers after virtual flattening was associated with the actual postoperative defect and best-corrected visual acuity (BCVA). Methods: Patients were included who had undergone successful MH surgery. The defects in the ELM and EZ after virtual flattening were modeled using in-house software. Main outcomes were postoperative defects in ELM and EZ at 2 months and BCVA at 12 months. Results: Fifty-eight patients were included. BCVA improved from 0.87 (0.31) logMAR pre-operatively to 0.26 (0.21) at 12 months (P < 0.001). For both the ELM and EZ, the predicted virtually flattened pre-operative defects were associated with the actual postoperative defects at 2 months (R2 = 0.33, P < 0.01 and R2 = 0.50, P < 0.01, respectively). There was a significant association of BCVA at 12 months (adjusted R2 = 0.85) with the pre-operative modeled area of the defect in the ELM (P < 0.01) and to a lesser extent with the defect in the EZ (P < 0.01) and base of the MH (P < 0.01). Conclusions: Virtually flattening of the pre-operative defect in the ELM provides important predictive information of visual acuity. Incorporation of tools into commercially available optical coherence tomography (OCT) devices to facilitate such measurements would provide the clinician with important prognostic information. Translational Relevance: We have developed methodology that can potentially be used to predict the postoperative state of the outer retinal layers and the associated visual outcome in patients undergoing surgery for MH.

At what cost is collagenase clostridium histolyticum viable for treating Peyronie's disease in a public healthcare system?

BACKGROUND: Collagenase clostridium histolyticum is a recognized non-surgical management for Peyronie's disease, licenced for use in the UK for patients with a palpable plaque and a curvature deformity of at least 30°. However, it is not currently funded for use within the National Health Service. Collagenase clostridium histolyticum has also recently been withdrawn from the European and other markets worldwide, but there is potential for this to be produced off-patent in the future. OBJECTIVES: To determine whether collagenase clostridium histolyticum is cost-neutral when compared to surgical management within a public health care system, using the National Health Service as an example. MATERIALS AND METHODS: Two published protocols for the administration of collagenase in Peyronie's disease were identified-the 'IMPRESS protocol' and the 'London protocol'. Costs were taken from published NHS literature. Surgical intervention rates after collagenase clostridium histolyticum administration and primary penile plication were taken from published literature. The costs of the two published protocols were calculated with costs of any repeat surgical intervention were included within each protocol per patient cost. RESULTS: At the current cost per vial of collagenase to the National Health Service, the IMPRESS protocol per patient costs £3,832.77 (143.7%) more than primary surgery, whilst the London protocol costs £70.77 (2.7%) more than primary surgery. DISCUSSION: At a cost of £548.41 per vial, collagenase administered under the London protocol would be a management option for Peyronie's disease cost neutral to primary corrective surgery. CONCLUSION: Central funding of collagenase in a public healthcare system would enable the management of Peyronie's disease to be moved to the outpatient setting. For this to be done at no additional cost to the NHS, it would require a cost reduction per vial of collagenase of £23.59 (4.1%), to a cost of £548.41.

EFFECT OF INVERTED INTERNAL LIMITING MEMBRANE FLAP ON CLOSURE RATE, POSTOPERATIVE VISUAL ACUITY, AND RESTORATION OF OUTER RETINAL LAYERS IN PRIMARY IDIOPATHIC MACULAR HOLE SURGERY.

PURPOSE: To investigate the role of an internal limiting membrane (ILM) flap in macular hole (MH) surgery on closure rate, visual acuity, and integrity of the outer retinal layers. METHODS: Retrospective, nonrandomized interventional analysis in which 117 eyes of 117 patients were included who had undergone pars-plana vitrectomy (PPV) and gas tamponade for primary idiopathic MH >400 µm with either conventional ILM peeling or with inverted ILM flap technique at The Royal Liverpool University Hospital between January 2016 and April 2018. Main outcome measures were closure of MH, best-corrected visual acuity (BCVA) at 3, 6, and 12 months, and restoration of external limiting membrane and ellipsoid zone (EZ) using optical coherence tomography. RESULTS: Macular hole closure rate was significantly higher in patients with an ILM flap (67/68; 98.53%) than in those with conventional ILM peeling (43/49; 87.76%) (P = 0.02). Both groups showed significant improvements in their preoperative to postoperative BCVA at 3 months from 1.07 (0.43) logarithm of the minimum angle of resolution (logMAR) (20/235 Snellen) to 0.71 (0.34) logMAR (20/103 Snellen) (P <0.001), but there was no significant difference between the two groups (P = 0.45, P = 0.71). We found significant associations between postoperative BCVA and preoperative BCVA (P < 0.01) and the integrity of the EZ (P < 0.01). In 35 patients who had follow-up to 12 months, there was a significant improvement in BCVA between 3, 6, and 12 months from 0.73 (0.45) logMAR (20/107 Snellen) to 0.53 (0.24) logMAR (20/68 Snellen) and to 0.35 (0.18) logMAR (20/45 Snellen), respectively (P < 0.01). There was no significant difference at these time periods between the two groups (P = 0.62, P = 0.21, P = 0.31). The integrity of the EZ also improved significantly between 3, 6, and 12 months (P = 0.01), irrespective of the presence of an ILM flap (P = 0.58), but with a trend toward delay in restoration in those patients with an ILM flap. The improvement in BCVA at 12 months, taking into account the age of the patient, size and duration of the MH, presence of an ILM flap, and preoperative BCVA was dependent on the state of the EZ (P = 0.01). CONCLUSION: In patients undergoing primary pars-plana vitrectomy for MH >400 µm, the presence of an inverted ILM flap was associated with a significantly higher closure rate than a conventional ILM peeling. Best-corrected visual acuity showed a strong correlation with the integrity of the EZ and both improved significantly between 3, 6, and 12 months, irrespective of the presence of an ILM flap.

Adalimumab for non-infectious uveitis: is it cost-effective?

BACKGROUND/AIMS: Uveitis is inflammation inside the eye. Our objective was to assess the cost-effectiveness of adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or panuveitis and to identify areas for future research. METHODS: A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the available relevant clinical and cost-effectiveness evidence. Data collected in two key randomised controlled trials (VISUAL I and VISUAL II) were used to estimate the interventions' effectiveness compared with the trials' comparator arms (placebo plus limited current practice (LCP)). The analysis was performed from the National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The estimated incremental cost-effectiveness ratios (ICERs) of adalimumab versus LCP for the base case are £92 600 and £318 075 per quality-adjusted life year (QALY) gained for active and inactive uveitis, respectively. In sensitivity analyses, the ICER varied from £15 579 to £120 653 and £35 642 to £800 775 per QALY for active and inactive uveitis. CONCLUSION: The estimated ICERs of adalimumab versus LCP are above generally accepted thresholds for cost-effectiveness in the UK. Adalimumab may be more cost-effective in patients with active uveitis at greater risk of blindness. However, there is an unmet need for additional primary data to provide more reliable estimates in several important areas, including effectiveness of adalimumab versus current practice (instead of LCP), incidence of long-term blindness, adalimumab effectiveness in avoiding blindness, and rates and time to remission while on adalimumab.

Dexamethasone implant for non-infectious uveitis: is it cost-effective?

BACKGROUND: Uveitis is inflammation inside the eye. The objective of this study is to assess the cost-effectiveness of a dexamethasone implant plus current practice (immunosuppressants and systemic corticosteroids) compared with current practice alone, in patients with non-infectious intermediate, posterior or pan-uveitis and to identify areas for future research. METHODS: A Markov model was built to estimate the costs and benefits of dexamethasone. Systematic reviews were performed to identify available relevant evidence. Quality of life data from the key randomised-controlled trial (HURON) was used to estimate the interventions' effectiveness compared with the trial's comparator arm (placebo plus limited current practice (LCP)). The analysis took a National Health Service and Personal Social Services perspective. Costs were calculated based on standard UK sources. RESULTS: The incremental cost-effectiveness ratio (ICER) of one dexamethasone implant compared with LCP is estimated as £19 509 per quality-adjusted life year (QALY) gained. The factors with the largest impact on the results were rate of blindness and relative proportion of blindness cases avoided by dexamethasone. Using plausible alternative assumptions, dexamethasone could be cost saving or it may be associated with an ICER of £56 329 per QALY gained compared with LCP. CONCLUSIONS: Dexamethasone is estimated to be cost-effective using generally accepted UK thresholds. However, there is substantial uncertainty around these results due to scarcity of evidence. Future research on the following would help provide more reliable estimates: effectiveness of dexamethasone versus current practice (instead of LCP), with subgroup analyses for unilateral and bilateral uveitis, incidence of long-term blindness and effectiveness of dexamethasone in avoiding blindness.

A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults.

BACKGROUND: Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira®; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex®; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis. DATA SOURCES: Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016. REVIEW METHODS: Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken. RESULTS: Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; p < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; p = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; p = 0.010) but not the VISUAL II trial (mean difference 2.12; p = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero (p < 0.014), the mean best corrected visual acuity improvement (p ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score (p < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness. LIMITATIONS: The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base. CONCLUSIONS: Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016041799. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Leukaemia diagnosed as a consequence of haematuria assessment: a case report.

INTRODUCTION: T-cell prolymphocytic leukaemia is a rare condition that constitutes around 2% of cases of small lymphocytic leukaemia in adults. It follows an aggressive clinical course with a poor prognosis. CASE PRESENTATION: We report a 55-year-old male who was diagnosed with T-cell prolymphocytic leukaemia following investigations for microscopic haematuria. Splenomegaly was identified on a plain abdominal radiograph and intravenous urography, thus triggering further investigations and diagnosis. CONCLUSION: Our case-report serves to remind us of the need to bear in mind other possible pathologies outwith our own area of expertise when interpreting results of any kind. This is perhaps increasingly important in the current era of increasing sub-specialisation throughout medicine.