Optical penetration models for practical prediction of femtosecond laser ablation of dental hard tissue.

OBJECTIVES: To develop and practically test high-precision femtosecond laser ablation models for dental hard tissue that are useful for detailed planning of automated laser dental restorative treatment. METHODS: Analytical models are proposed, derived, and demonstrated for practical calculation of ablation rates, ablation efficiency and ablated morphology of human dental enamel and dentin using femtosecond lasers. The models assume an effective optical attenuation coefficient for the irradiated material. To achieve ablation, it is necessary for the local energy density of the attenuated pulse in the hard tissue to surpass a predefined threshold that signifies the minimum energy density required for material ionization. A 1029 nm, 40 W carbide 275 fs laser was used to ablate sliced adult human teeth and generate the data necessary for testing the models. The volume of material removed, and the shape of the ablated channel were measured using optical profilometry. RESULTS: The models fit with the measured ablation efficiency curve against laser fluence for both enamel and dentin, correctly capturing the fluence for optimum ablation and the volume of ablated material per pulse. The detailed shapes of a 400-micrometer wide channel and a single-pulse width channel are accurately predicted using the superposition of the analytical result for a single pulse. CONCLUSIONS: The findings have value for planning automated dental restorative treatment using femtosecond lasers. The measurements and analysis give estimates of the optical properties of enamel and dentin irradiated with an infrared femtosecond laser at above-threshold fluence and the proposed models give insight into the physics of femtosecond laser processing of dental hard tissue.

Subfemtowatt Laser Phase Tracking.

Low power optical phase tracking is an enabling capability for intersatellite laser interferometry, as minimum trackable power places significant constraints on mission design. Through the combination of laser stabilization and control-loop parameter optimization, we have demonstrated continuous tracking of a subfemtowatt optical field with a mean time between slips of more than 1000 s. Comparison with analytical models and numerical simulations verified that the observed experimental performance was limited by photon shot noise and unsuppressed laser frequency fluctuations. Furthermore, with two stabilized lasers, we have demonstrated 100 min of continuous phase tracking of Gravity Recovery and Climate Experiment (GRACE)-like signal dynamics with an optical carrier ranging in power between 1-7 fW with zero cycle slips. These results indicate the feasibility of future interspacecraft laser links operating with significantly reduced received optical power.

Perceptions and Attitudes Regarding Medical Device Development in Canada Among Canadian Innovators: A Qualitative Study.

OBJECTIVES: The Canadian medical device industry presents unique challenges to innovators. However, little attention has been paid to exploring the distinct experience of Canadian medical device innovators in the literature. The objective of this study is to explore the experience of Canadian innovators in navigating this industry, with a focus on their perceptions and attitudes towards the use of health economic evaluation. METHODS: Semi-structured interviews were conducted using virtual conferencing technology. All participants were C-level employees of small- and medium-sized enterprises (SMEs) with adequate knowledge of their company's overall strategy. Qualitative data were analyzed to reveal emerging themes. RESULTS: Interviews were performed with ten participants. Forty percent of participants rated themselves as having either minimal or basic knowledge of health economics. Thirty percent of participants had not pursued early economic evaluation of their device, while 90% rated health economics as being either "Quite important" or "Very important" to their company. The perception of increased barriers to successful device adoption in Canada relative to the USA was a prominent sentiment among participants, with 50% expressing discontentment with either the device approval process or health technology assessment process in Canada. Twenty percent stated that their primary target market involved the USA and/or other international jurisdictions. CONCLUSION: Canadian medical device innovators appear to understand the importance of health economic evaluation in the innovation process. However, they report difficulty with device approval and adoption, with some innovators focusing their efforts outside of Canada altogether. Further research should be directed toward understanding how to better support SMEs, given that they are a tremendous source of growth for the Canadian medical device industry.

Exploring the approach to parameter uncertainty in early economic evaluations of surgical technology - a systematic review.

INTRODUCTION: The role of early economic evaluation (EEE) in the development of medical technology has been increasingly recognized; however, data on the use of EEE in surgical technology are sparse. The objective of this review was to explore the use of EEE in the development of surgical technologies, with emphasis on how uncertainty has been addressed. AREAS COVERED: A systematic review was conducted, and original articles employing any form of EEE of surgical technology were selected for review, with 10 studies included in the analysis. These studies demonstrated significant variation in the approach to managing parameter uncertainty, specifically regarding the type of analysis used and the inclusion of effectiveness parameters in sensitivity analysis. The conclusions drawn did not appear to factor in uncertainty in the models. EXPERT OPINION: Approaches to handling parameter uncertainty in previous EEEs of surgical technology have been limited, with some studies failing to address parameter uncertainty. In addition, EEEs do not appear to follow established guidelines with respect to the use of sensitivity analyses. It is important that EEEs of surgical technology address parameter uncertainty in order to draw more robust conclusions from the analysis and allow investors to consider this uncertainty when making investment decisions.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions: erratum.

We found a calculation error affecting the scaling of results presented in Figure 7 of our article "Absolute frequency readout derived from ULE cavity for next generation geodesy missions" [Opt. Express2926014 (2021)10.1364/OE.434483] . The corrected Figure 7 is published here.

Detection statistics for coherent RMCW LiDAR.

This paper presents an analytical model and experimental validation for the detection performance and false-alarm rates for phase-encoded random modulation continuous-wave (RMCW) LiDAR. Derivation of the model focuses on propagating the effects of relevant noise sources through the system to determine an analytical expression for the detection rate, expressed by the probability of detection. The model demonstrates that probability of detection depends only on three factors: i) the mean signal-to-noise ratio (SNR) of the measurement; ii) the measurement integration time; and iii) speckle-induced intensity noise. The predicted analytical relationship between measurement SNR and probability of detection was validated by numerical simulations and experimental demonstrations in both a controlled fiber channel and under fully-developed speckle conditions in an uncontrolled free-space channel.

Absolute frequency readout derived from ULE cavity for next generation geodesy missions.

The next generation of Gravity Recovery and Climate Experiment (GRACE)-like dual-satellite geodesy missions proposals will rely on inter-spacecraft laser interferometry as the primary instrument to recover geodesy signals. Laser frequency stability is one of the main limits of this measurement and is important at two distinct timescales: short timescales over 10-1000 seconds to measure the local gravity below the satellites, and at the month to year timescales, where the subsequent gravity measurements are compared to indicate loss or gain of mass (or water and ice) over that period. This paper demonstrates a simple phase modulation scheme to directly measure laser frequency change over long timescales by comparing an on-board Ultra-Stable Oscillator (USO) clocked frequency reference to the Free Spectral Range (FSR) of the on-board optical cavity. By recording the fractional frequency variations the scale correction factor may be computed for a laser locked to a known longitudinal mode of the optical cavity. The experimental results demonstrate a fractional absolute laser frequency stability at the 10 ppb level (10-8) at time scales greater than 10 000 seconds, likely sufficient for next generation mission requirements.

High stability laser locking to an optical cavity using tilt locking.

This paper describes, to our knowledge, the first demonstration of high performance tilt locking, a method of stabilizing laser frequency to an optical reference cavity using a spatial-mode readout technique. The experiment utilized a traveling wave cavity with a finesse of approximately 10,000, housed in a thermally controlled vacuum chamber. The tilt locking method in a double pass configuration has promising performance in the 100 µHz-1 Hz band, including surpassing the Gravity Recovery and Climate Experiment (GRACE) Follow-On laser ranging interferometer requirement. Tilt locking offers a number of benefits such as high sensitivity, low cost, and simple implementation and therefore should be considered for future applications requiring high performance laser locking, such as future laser-based satellite geodesy missions and the Laser Interferometer Space Antenna.

A Multicenter Randomized Controlled Trial Comparing Safety, Efficacy, and Cost-effectiveness of the Surgisis Anal Fistula Plug Versus Surgeon's Preference for Transsphincteric Fistula-in-Ano: The FIAT Trial.

OBJECTIVE: To undertake a randomized comparison of the Biodesign Surgisis anal fistula plug against surgeon's preference in treating cryptoglandular transsphincteric fistula-in-ano. SUMMARY BACKGROUND DATA: The efficacy of the Biodesign Surgisis anal fistula plug in healing anal fistulae is uncertain. METHODS: Participants were randomized to the fistula plug with surgeon's preference (advancement flap, cutting seton, fistulotomy, Ligation of the Intersphincteric Fistula Tract procedure). The primary outcome was faecal incontinence quality of life (FIQoL) at 12-months. Secondary outcomes were fistula healing, incontinence rates, and complication and reintervention rates. RESULTS: Between May 2011 and March 2016, 304 participants were randomized to fistula plug or surgeon's preference. No differences were seen in FIQoL between the 2 groups at 12 months. Clinical fistula healing was reported in 66/122 (54%) of the fistula plug and 66/119 (55%) of the surgeon's preference groups at 12 months. Fecal incontinence rates improved marginally in both the groups. Complications and reinterventions were frequent, with significantly more complications in the fistula plug group at 6-weeks (49/142, 35% vs 25/137, 18%; P=0.002). The mean total costs were £2738 (s.d. £1151) for the fistula plug and £2308 (s.d. £1228) for the surgeon's preference group (mean difference +£430, P=0.0174). The average total quality adjusted life years (QALYs) gained was marginally higher in the fistula plug group. The fistula plug was 35% to 45% likely to be cost-effective across a willingness to pay threshold of £20,000 to £30,000 / QALY. CONCLUSIONS: The Biodesign Surgisis anal fistula plug is associated with similar FIQoL and healing rates to surgeon's preference at 12 months. Higher costs and highly uncertain gains in QALYs mean that the fistula plug may not be considered as a cost-effective treatment in the UK NHS.

Early Economic Evaluation to Identify the Necessary Test Characteristics of a New Typhoid Test to be Cost Effective in Ghana.

BACKGROUND: In Ghana, there are issues with the diagnosis of typhoid fever; these include delays in diagnosis, concerns about the accuracy of current tests, and lack of availability. These issues highlight the need for the development of a rapid, accurate, and easily accessible diagnostic test. The aim of this study was to conduct an early economic analysis of a hypothetical rapid test for typhoid fever diagnosis in Ghana and identify the necessary characteristics of the test for it to be cost effective in Ghana. METHODS: An early cost-utility analysis was conducted using a decision tree parameterized with secondary data sources, with reasonable assumptions made for unknown parameters. The patient population considered is individuals presenting with symptoms suggestive of typhoid fever at a healthcare facility in Ghana; a time horizon of 180 days and the Ghanaian national health service perspective were adopted for the analysis. Extensive sensitivity analysis was undertaken, including headroom analysis. RESULTS: The results here show that for a hypothetical test to perform better than the existing test (Widal) in terms of QALYs gained and cost effectiveness, it is necessary for it to have a high specificity (at least 70%) and should not be priced more than US$4. The overall value of conducting research to reduce uncertainty (over 5 years) is US$3287. CONCLUSION: The analysis shows the potential for the hypothetical test to replace the Widal test and the market potential of developing a new test in the Ghanaian setting.

Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives.

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a "quick and dirty" approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution.

Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.

When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m2). Patients underwent weekly GFR measurement by iohexol clearance over four consecutive weeks. Simultaneously, GFR was estimated using the MDRD, CKD-EPIcreatinine, CKD-EPIcystatinC and CKD-EPIcreatinine+cystatinC equations. Within-subject biological variation expressed as a percentage [95% confidence interval] for the MDRD (5.0% [4.3-6.1]), CKD-EPIcreatinine (5.3% [4.5-6.4]), CKD-EPIcystatinC (5.3% [4.5-6.5]), and CKD-EPIcreatinine+cystatinC (5.0% [4.3-6.2]) equations were broadly equivalent. The within-subject biological variation for MDRD and CKD- EPIcreatinine+cystatinC estimated GFR were each significantly lower than that of the measured GFR (6.7% [5.6-8.2]). Reference change values, the point at which a true change in a biomarker in an individual can be inferred to have occurred with 95% probability were calculated. By the MDRD equation, positive and negative reference change values were 15.1% and 13.1% respectively. If an individual's baseline MDRD estimated GFR (ml/min per 1.73 m2) was 59, significant increases or decreases would be to values over 68 or under 51 respectively. Within-subject variability of estimated GFR was lower than measured GFR. Reference change values can be used to understand GFR changes in clinical practice. Thus, estimates of GFR are at least as reliable as measured GFR for monitoring patients over time.

Anal fistula plug versus surgeon's preference for surgery for trans-sphincteric anal fistula: the FIAT RCT.

BACKGROUND: The aim of fistula surgery is to eradicate the disease while preserving anal sphincter function. The efficacy of the Surgisis® anal fistula plug (Cook Medical, Bloomington, IN, USA) in the treatment of trans-sphincteric fistula-in-ano has been variably reported. OBJECTIVES: To undertake a randomised comparison of the safety and efficacy of the Surgisis anal fistula plug in comparison with surgeon's preference for the treatment of trans-sphincteric anal fistulas. DESIGN: A randomised, unblinded, parallel-arm, prospective, multicentre clinical trial. SETTING: Hospitals in the UK NHS involving colorectal surgeons accredited by the Association of Coloproctology of Great Britain and Ireland. PARTICIPANTS: Adult patients suffering from trans-sphincteric fistula-in-ano of cryptoglandular origin. INTERVENTIONS: Patients were randomised on a 1 : 1 basis to either the fistula plug or the surgeon's preference [e.g. fistulotomy, cutting seton, advancement flap or ligation of intersphincteric fistula tract (LIFT) procedure]. MAIN OUTCOME MEASURES: The primary outcome measure was quality of life as measured by the Faecal Incontinence Quality of Life (FIQoL) questionnaire at 12-month follow-up. Secondary outcome measures included clinical and radiological fistula healing rates, faecal incontinence rates, complications rates, reintervention rates and cost-effectiveness. RESULTS: Between May 2011 and March 2016, 304 participants were recruited (152 fistula plug vs. 152 surgeon's preference). No difference in FIQoL score between the two trial groups was seen at the 6-week, 6-month or 12-month follow-up. Clinical evidence of fistula healing was reported in 66 of 122 (54%) participants in the fistula plug group and in 66 of 119 (55%) participants in the surgeon's preference group at 12 months. Magnetic resonance imaging (MRI) showed fistula healing in 54 of 110 (49%) participants in the fistula plug group and in 63 of 112 (56%) participants in the surgeon's preference group. Variation in 12-month clinical healing rates was observed: 55%, 64%, 75%, 53% and 42% for fistula plug, cutting seton, fistulotomy, advancement flap and LIFT procedure, respectively. Faecal incontinence rates were low at baseline, with small improvement in both groups post treatment. Complications and reinterventions were frequent. The mean total costs were £2738 [standard deviation (SD) £1151] in the fistula plug group and £2308 (SD £1228) in the surgeon's preference group. The average total quality-adjusted life-years (QALYs) gain was much smaller in the fistula plug group (0.829, SD 0.174) than in the surgeon's preference group (0.790, SD 0.212). Using multiple imputation and probabilistic sensitivity analysis, and adjusting for differences in baseline EuroQol-5 Dimensions, three-level version utility, there was a 35-45% chance that the fistula plug was as cost-effective as surgeon's preference over a range of thresholds of willingness to pay for a single QALY of £20,000-30,000. LIMITATIONS: Limitations include a smaller sample size than originally calculated, a lack of blinding that perhaps biased patient-reported outcomes and a lower compliance rate with MRI at 12-month follow-up. CONCLUSIONS: The Surgisis anal fistula plug is associated with similar FIQoL score to surgeon's preference at 12-month follow-up. The higher costs and highly uncertain and small gains in QALYs associated with the fistula plug mean that this technology is unlikely to be considered a cost-effective use of resources in the UK NHS. FUTURE WORK: Further in-depth analysis should consider the clinical and MRI characteristics of fistula-in-ano in an attempt to identify predictors of fistula response to treatment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78352529. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 21. See the NIHR Journals Library website for further project information.

Fistula-in-ano is a common condition in which the inside of the anus is in communication with the outside skin. It is a cause of long-term suffering owing to recurrent infection. Many surgical operations have been proposed to treat fistula-in-ano, with varying degrees of success. These carry the risk of faecal incontinence. The aim of the Fistula-In-Ano Trial (FIAT) was to assess the benefits of a new technology, the Surgisis^® anal fistula plug (Cook Medical, Bloomington, IN, USA), compared with other surgical techniques. The FIAT involved 304 participants; 152 participants were treated with the fistula plug and 152 participants were treated with an alternative surgical technique. There were no differences in quality of life (QoL) among participants treated with the fistula plug compared with those receiving other treatments when assessed 12 months following the operation. Successful fistula healing was achieved in 54% of fistula plug-treated participants and in 55% of participants treated with an alternative technique at 12 months following the operation. Few patients suffered from faecal incontinence before their operation and there was a slight improvement following treatment with the fistula plug and other surgical treatments. The only difference seen between the group treated with the fistula plug and those receiving other surgical treatments was in the complication rate at the 6-week assessment time, with the fistula plug group having higher rates of unexpected pain. Economic analysis of the fistula plug compared with the other surgical treatments showed that the fistula plug was more expensive and only produced very small improvements in QoL. On this basis, it is unlikely that decision-makers in the NHS will support the routine use of the fistula plug.

Model-based economic evaluations of diagnostic point of care tests were rarely fit for purpose.

OBJECTIVES: Linked evidence models are recommended to predict health benefits and cost-effectiveness of diagnostic tests. We considered how published models accounted for changes in patient pathways that occur with point of care tests (POCTs) and their impact on patient health and costs. STUDY DESIGN AND SETTING: Model-based evaluations of diagnostic POCTs published from 2004 to 2017 were identified from searching six databases. For each model, we assessed the outcomes considered, and whether reduced time to diagnosis and increased access to testing affected patient health and costs. RESULTS: Seventy-four model-based evaluations were included: 95% incorporated evidence on test accuracy, but 34% only assessed intermediate outcomes such as rates of correct diagnosis. Of 54 models where POCTs reduced testing time, 39% addressed the economic and 37% addressed the health benefits of faster diagnosis. No model considered differences in access to tests. CONCLUSION: Many models fail to capture the effects of POCTs in increasing access, advancing speed of diagnosis and treatment, and reducing anxiety and the associated costs. Many only consider the impact of testing from changes in accuracy. Ensuring models incorporate changes in patient pathways from faster and more accessible testing will lead to economic evaluations that better reflect the impact of POCTs.

An early analysis of the cost-effectiveness of a diagnostic classifier for risk stratification of haematuria patients (DCRSHP) compared to flexible cystoscopy in the diagnosis of bladder cancer.

BACKGROUND: Urothelial bladder cancer (UBC) is the 5th most common cancer in Western societies. The most common symptom of UBC is haematuria. Cystoscopy the gold standard for UBC detection, allows direct observation of the bladder, but is expensive, invasive, and uncomfortable. This study examines whether an alternative new urine-based diagnostic test, the DCRSHP, is cost-effective as a triage diagnostic tool compared to flexible cystoscopy in the diagnosis of UBC in haematuria patients. METHODS: A model-based cost-utility analysis using cost per quality adjusted life year and life year gained, parameterised with secondary data sources. RESULTS: If the DCRSHP is targeted at haematuria patients at lower risk of having bladder cancer e.g. younger patients, non-smokers, then it can be priced as high as £620, and be both effective and cost-effective. Sensitivity analysis found that DCRSHP is approximately 80% likely to be cost-effective across all willingness to pay values (for a QALY) and prevalence estimates. CONCLUSION: This analysis shows the potential for a non-invasive test to be added to the diagnostic pathway for haematuria patients suspected of having UBC. If the DCRSHP is applied targeting haematuria patients at low risk of UBC, then it has the potential to be both effective and cost-effective.

MRI versus laparoscopy to diagnose the main causes of chronic pelvic pain in women: a test-accuracy study and economic evaluation.

BACKGROUND: Chronic pelvic pain (CPP) symptoms in women are variable and non-specific; establishing a differential diagnosis can be hard. A diagnostic laparoscopy is often performed, although a prior magnetic resonance imaging (MRI) scan may beneficial. OBJECTIVES: To estimate the accuracy and added value of MRI in making diagnoses of (1) idiopathic CPP and (2) the main gynaecological causes of CPP. To quantify the impact MRI can have on decision-making with respect to triaging for therapeutic laparoscopy and to conduct an economic evaluation. DESIGN: Comparative test-accuracy study with cost-effectiveness modelling. SETTING: Twenty-six UK-based hospitals. PARTICIPANTS: A total of 291 women with CPP. METHODS: Pre-index information concerning the patient's medical history, previous pelvic examinations and ultrasound scans was collected. Women reported symptoms and quality of life at baseline and 6 months. MRI scans and diagnostic laparoscopy (undertaken and interpreted blind to each other) were the index tests. For each potential cause of CPP, gynaecologists indicated their level of certainty that the condition was causing the pelvic pain. The analysis considered both diagnostic laparoscopy as a reference standard for observing structural gynaecological causes and consensus from a two-stage expert independent panel for ascertaining the cause of CPP. The stage 1 consensus was based on pre-index, laparoscopy and follow-up data; for stage 2, the MRI scan report was also provided. The primary analysis involved calculations of sensitivity and specificity for the presence or absence of each structural gynaecological cause of pain. A decision-analytic model was developed, with a 6-month time horizon. Two strategies, laparoscopy or MRI, were considered and populated with study data. RESULTS: Using reference standards of laparoscopic and expert panel diagnoses, MRI scans had high specificity but poor sensitivity for observing deep-infiltrating endometriosis, endometrioma, adhesions and ovarian cysts. MRI scans correctly identified 56% [95% confidence interval (CI) 48% to 64%] of women judged to have idiopathic CPP, but missed 46% (95% CI 37% to 55%) of those considered to have a gynaecological structural cause of CPP. MRI added significant value, over and above the pre-index information, in identifying deep-infiltrating endometriosis (p = 0.006) and endometrioma (p = 0.02) as the cause of pain, but not for other gynaecological structural causes or for identifying idiopathic CPP (p = 0.08). Laparoscopy was significantly more accurate than MRI in diagnosing idiopathic CPP (p < 0.0001), superficial peritoneal endometriosis (p < 0.0001), deep-infiltrating endometriosis (p < 0.0001) and endometrioma of the ovary (p = 0.02) as the cause of pelvic pain. The accuracy of laparoscopy appeared to be able to rule in these diagnoses. Using MRI to identify women who require therapeutic laparoscopy would lead to 369 women in a cohort of 1000 receiving laparoscopy unnecessarily, and 136 women who required laparoscopy not receiving it. The economic analysis highlighted the importance of the time horizon, the prevalence of CPP and the cut-off values to inform the sensitivity and specificity of MRI and laparoscopy on the model results. MRI was not found to be a cost-effective diagnostic approach in any scenario. CONCLUSIONS: MRI was dominated by laparoscopy in differential diagnosis of women presenting to gynaecology clinics with CPP. It did not add value to information already gained from history, examination and ultrasound about idiopathic CPP and various gynaecological conditions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13028601. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 40. See the NIHR Journals Library website for further project information.

Economic evaluation of typhoid - a review.

INTRODUCTION: To evaluate the potential economic value and likely impact of a hypothetical rapid test in its early stages of development requires the use of models. The model structure and the type of model (dynamic/static) to employ are key considerations. The aim of the review was to explore the literature on typhoid economic evaluations and to explore the types of models that have been previously adopted in this setting for test-treat evaluations and to capture data on model inputs that may be useful for a de novo model. AREAS COVERED: A systematic review was conducted to identify economic evaluations focused on typhoid in established literature databases. Eight studies were identified and included for narrative synthesis. The review has revealed that there have been relatively few economic evaluations that have focused on typhoid fever, all of which have focused on the impact of interventions at the population level (vaccination) but not the individual level (test-treat strategies). EXPERT COMMENTARY: Under certain circumstances, either a static model or a transmission dynamic model may be appropriate in the evaluation of an intervention for typhoid fever. Typhoid test-treat modeling represents a gray area where further work is needed.

Integrating Qualitative Techniques in Model Development: A Case Study Using the Framework Approach.

BACKGROUND: Despite their potential, there is limited uptake of formal qualitative methods in model development by modellers and health economists. The aim of this case study was to highlight in a real-world context how a qualitative approach has been applied to gain insight into current practice (delineating existing care pathways) for typhoid fever in Ghana, which can then assist in model structure conceptualisation in a model-based cost-effectiveness analysis. METHODS: The perspectives of a range of healthcare professionals working in different settings and across different practices in the Eastern region of Ghana were captured with a self-administered survey using open-ended questions and analysed using the framework method. RESULTS: A total of 51 completed questionnaires were retrieved representing a 73% response rate. It was found that two main care pathways for typhoid fever exist in Ghana and there was no consensus on how a new test might be applied to the existing pathways. CONCLUSION: The two settings in Ghana have different care pathways and any cost-effectiveness analysis should consider the alternative pathways separately. This study demonstrated that framework analysis is a qualitative methodology that is likely to be accessible and feasible across a wide range of health economic settings.

Exploring the roles of urinary HAI-1, EpCAM & EGFR in bladder cancer prognosis & risk stratification.

OBJECTIVES: To investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions. RESULTS: After accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03). PATIENTS AND METHODS: Urinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken. CONCLUSION: Urinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients.