Health Economic Analysis Research Articles

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

Health-related quality of life in patients with conditions affecting the hand: meta-analysis.

Health state utility values provide the quality component of quality-adjusted life years and are essential for health economic analyses, such as the National Institute for Health and Care Excellence Technology Appraisal. The aims of this systematic review were to: catalogue utility values for health states experienced by patients with hand conditions; provide pooled utility estimates for common hand conditions; and determine how utilities have been estimated. A PRISMA-compliant systematic review and meta-analysis was conducted (registered in PROSPERO, the international prospective register of systematic reviews (CRD42021226098)). Five databases were searched from inception until April 2023 (Embase, MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL)). All studies that reported primary utility values for hand health states in adult patients were eligible for inclusion. Pooled utility estimates were determined across conditions and intervention status using random-effects meta-analysis. A total of 10 254 articles were identified; 57 studies met the full inclusion criteria and reported 363 distinct health state utility values. Health state utility values were estimated using a range of methods; the most common measure was the EQ-5D. Pooled utility estimates for carpal tunnel syndrome and hand osteoarthritis before surgical intervention were 0.69 (95% c.i. 0.66 to 0.73) and 0.63 (95% c.i. 0.60 to 0.67) respectively. Pooled utility estimates for patients with untreated carpal tunnel syndrome and hand osteoarthritis are 11% and 18% lower than age-matched population norms respectively. Hand conditions have a significant detrimental impact on health-related quality of life and this study provides catalogued utility values for use in future economic analyses to support the delivery of value-based hand surgery.

A person-centred consultation intervention to improve shared decision-making about, and uptake of, osteoporosis medicines (iFraP): a pragmatic, parallel-group, individual randomised controlled trial protocol.

Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person's life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations.Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation. The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics. The iFraP trial will answer important questions about the effectiveness of the new 'iFraP' osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines. ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407.

Drivers and recent trends of hospitalisation costs related to acute pulmonary embolism.

The socio-economic burden imposed by acute pulmonary embolism (PE) on European healthcare systems is largely unknown. We sought to determine temporal trends and identify cost drivers of hospitalisation for PE in Germany. We analysed the totality of reimbursed hospitalisation costs in Germany (G-DRG system) in the years 2016-2020. Overall, 484 884 PE hospitalisations were coded in this period. Direct hospital costs amounted to a median of 3572 (IQR, 2804 to 5869) euros, resulting in average total reimbursements of 710 million euros annually. Age, PE severity, comorbidities and in-hospital (particularly bleeding) complications were identified by multivariable logistic regression as significant cost drivers. Use of catheter-directed therapy (CDT) constantly increased (annual change in the absolute proportion of hospitalisations with CDT + 0.40% [95% CI + 0.32% to + 0.47%]; P < 0.001), and it more than doubled in the group of patients with severe PE (28% of the entire population) over time. Although CDT use was overall associated with increased hospitalisation costs, this association was no longer present (adjusted OR 1.02 [0.80-1.31]) in patients with severe PE and shock; this was related, at least in part, to a reduction in the median length of hospital stay (for 14.0 to 8.0days). We identified current and emerging cost drivers of hospitalisation for PE, focusing on severe disease and intermediate/high risk of an adverse early outcome. The present study may inform reimbursement decisions by policymakers and help to guide future health economic analysis of advanced treatment options for patients with PE.

Outcome of Different Surgical Repair Techniques for Rhegmatogenous Retinal Detachment-A Health Economic Analysis in the Split-Dalmatia County, Croatia.

Purpose: The goal of this research is to investigate the characteristics and surgical techniques for repairing rhegmatogenous retinal detachment (RRD) and their influence on anatomical and functional success of the treatment with a special emphasis on the economic costs and outcome quality-adjusted life years (QALYs) of the procedures. Methods: This retrospective study analyzed data from 151 patients with RRD treated at the Department of Ophthalmology, Clinical Hospital Centre Split, Croatia, in a 3-year period, using one of three surgical techniques: pneumoretinopexy (PR), scleral buckling (SB) or pars plana vitrectomy (PPV), followed-up for at least 6 months. Demographic, pre- and post-operative ophthalmic exam parameters and surgical technique used were collected accordingly. Statistical analysis of the influence of the studied parameters upon anatomical and functional outcomes was performed, as well as health economic analysis on costs and derived utilities/QALYs of these surgical methods. Results: Of all patients, 130 (86%) were successfully operated on, and 21 patients (14%) required another surgical procedure. No statistically significant differences in the anatomical success between the 3 surgical techniques were found. However, the functional outcome (based on the final best corrected visual acuity (BCVA)) differed significantly. Despite improvement in the final BCVA, BCVA ≥ 0.5 was achieved in only 52 (34.4%) patients. The final BCVA showed significant association with the time elapsed from the onset of RRD to the surgical intervention, pre-operative BCVA, macular- and preoperative lens- status and type of surgery. The estimated diagnosis-related group (DRG) cost for day and inpatient surgery was based upon existing DRG cost for PPV, which for PR and SB was calculated accordingly. Based upon the success of the procedure and visual outcome, the overall calculated QALYs for PR and SB appeared to be similar, while the QALYs were lower for PPV. Conclusions: The success rate of treating RRD mostly depends on performing an early surgical procedure (especially in the case of attached macula), identification of all retina tears and, most importantly, choosing the appropriate surgical technique. Decisions on treatment for RRD should also be based upon cost-effective and QALYs-assessed procedures, especially in countries like Croatia, where limited healthcare resources exist. This study shows PR to be efficient and most cost-effective for RRD repairment in appropriate cases.

Wellbeing Impact Study of High-Speed 2 (WISH2): Protocol for a mixed-methods examination of the impact of major transport infrastructure development on mental health and wellbeing.

Although research has demonstrated that transport infrastructure development can have positive and negative health-related impacts, most of this research has not considered mental health and wellbeing separately from physical health. There is also limited understanding of whether and how any effects might be experienced differently across population groups, whether this differs according to the stage of development (e.g. planning, construction), and how changes to planned infrastructure may affect mental health and wellbeing. This paper presents a protocol for the Wellbeing Impact Study of HS2 (WISH2), which seeks to address these questions using a high-speed rail development in the UK as an applied example. WISH2 is a 10-year, integrated, longitudinal, mixed-methods project using general practices (primary medical care providers in the UK) as an avenue for participant recruitment and for providing a geographically defined population for which aggregated data on mental health indicators are available. The research comprises: (i) a combined longitudinal and repeated cross-sectional cohort study involving multiple waves of survey data collection and data from medical records; (ii) longitudinal, semi-structured interviews and focus groups with residents and community stakeholders from exposed areas; (iii) analysis of administrative data aggregated at the general practice population level; and (iv) health economic analysis of mental health and wellbeing impacts. The study findings will support the development of strategies to reduce negative impacts and/or enhance positive mental health and wellbeing impacts of high-speed rail developments and other large-scale infrastructure projects.

Pediatric acute hospitalization for anorexia nervosa: an economic evaluation.

Anorexia nervosa (AN) is a psychiatric disorders which may potentially led to a high risk of health medical complications, suicide and self-harming behaviour. Since Covid-19 pandemic onset in March 2020, evidence suggested an increase occurrence of AN. The main aim of the retrospective analysis is to define the cost of hospitalization in the acute phase (HAP) at IRCCS Bambino Gesù Children Hospital, Rome, Italy, over 2 years study. Secondary purposes are defining the main risk factors for a prolonged hospitalization (including age, sex and comorbidities) and the possible influence of Covid-19 pandemic on AN admission and hospital stay. for the purpose of the study, we included children and adolescents aged less than 18 years, admitted to IRCCS Bambino Gesù Children Hospital, Rome, Italy, with a diagnosis of AN. Medical costs were calculated consulting the Lazio Regional Health Service Tariffs. Basing on the date of hospital admission, patients were later divided into two subgroups: subgroup A included patients hospitalized prior than Covid-19 onset (from March 2019 to February 2020) and subgroup B those admitted after (from March 2020 to October 2022). a total of 260 patients has been included in the study with a median age of 15 years (range 6-18 years). The total health care cost of AN hospitalized patients was of EUR 3,352,333 with a median cost of EUR 11,124 for each admission (range EUR 930 - 45,739) and a median daily cost of EUR 593 (range EUR 557-930). Median cost was higher in case of comorbidities, guarded patients, enteral feeding. A prolonged hospitalization has been documented in subgroup A with a higher economic burden. the economic burden of eating disorders is of note. Adequate sanitary policies as well as health economic analyses are required to gain insight into the cost-effectiveness of AN management. 2526-OPBG-2021.

Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention: Rationale and Design of the CHIP-BCIS3 Randomized Controlled Trial.

Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.

Findings from a pragmatic cluster randomised controlled feasibility trial of a music and dance programme for community dwelling older adults

IntroductionFunctional decline, chronic illness, reduced quality of life and increased healthcare utilisation are common in older adults. Evidence suggests music and dance can support healthy ageing in older adults. This study explored the feasibility, potential for effect and cost effectiveness of the Music and Movement for Health (MMH) programme among community-dwelling older adults using a pragmatic cluster-randomised, controlled feasibility trial design. MethodsCommunity-dwelling adults aged 65 years or older were recruited to seven clusters in the Mid-West region of Ireland. Clusters were block randomised to either the MMH intervention or control. Primary feasibility outcomes included recruitment, retention, adherence, fidelity, and safety. Secondary outcomes measured physical activity, physical and cognitive performance, and psychosocial well-being, along with healthcare utilisation were assessed at baseline and after 12 weeks. ResultsThe study successfully met feasibility targets, with recruitment (n = 100), retention (91 %), adherence (71 %), data completeness (92 %) and intervention fidelity (21 out of 24) all meeting predetermined criteria. Both groups exhibited an increase in self-reported physical activity and improved physical function. Participants in the intervention group scored consistently better in psychosocial measures compared to the control group at follow-up. The health economic analysis confirmed the feasibility of the methodology employed and points to the potential cost-effectiveness of the MMH relative to the control or no organised programme. Discussion and ImplicationsThe MMH intervention and study design were found to be feasible and acceptable with important findings to inform future evaluation of the clinical and cost-effectiveness of a definitive randomised controlled trial.

Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial

BackgroundRadiofrequency (RF) treatment of the genicular nerves reduces chronic knee pain in patients with osteoarthritis (OA) or persistent postsurgical pain (PPSP) after total knee arthroplasty (TKA). The objective of this...

Direct medical cost related to the management of pemphigus: A pilot Tunisian study.

Pemphigus is a therapeutically challenging disease with high morbidity and economic burden. First-line prescription of rituximab remains limited in Tunisia due to its high cost. Systemic steroids remain the standard of care but are associated with a major risk of morbidities and higher treatment costs. To assess the direct medical costs of pemphigus in Tunisia. Retrospective estimation of direct medical costs during the 18 months following the diagnosis using the "bottom-up approach" in the Dermatology Department of Hedi Chaker Hospital, Sfax, Tunisia. Total medical costs were estimated at 38745.7 €, with an average cost of 1 210 € per patient and per year: paraclinical investigations (46%), medical treatment (30%), hospitalization (21%) and outpatient visits (3%). The average cost was the highest in the age group of 15-24 years (1553 €). Treatment costs related to corticosteroid-induced morbidity were estimated at 1208 €. The management of pemphigus in Tunisia needs to be adapted to take into account the health economic analysis in order to reduce overall disease costs and the burden of steroid-induced morbidities.

Precision medicine in cardiovascular therapeutics: Evaluating the role of pharmacogenetic analysis prior to drug treatment.

Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin. Furthermore, the CYP2C19 polymorphism influences the pharmacokinetics and safety of the novel hypertrophic cardiomyopathy inhibitor, mavacamten. In this review, we critically assess the clinical application of pharmacogenomics in cardiovascular disease and delineate present and future utilization of pharmacogenomics. This includes insights into identifying missing heritability, the integration of whole genome sequencing and the application of polygenic risk scores to enhance the precision of personalized drug therapy. Our discussion encompasses health economic analyses that underscore the cost benefits associated with pre-emptive genotyping for warfarin and clopidogrel treatments, albeit acknowledging the need for further research in this area. In summary, we contend that cardiovascular pharmacogenomic analyses are underpinned by a wealth of evidence, and implementation is already occurring for some of these gene-drug pairs, but as with any area of medicine, we need to continually gather more information to optimize the use of pharmacogenomics in clinical practice.

Direct-to-consumer telemedicine in primary care settings: A scoping review of contemporary empirical literature.

This study comprehensively reviews the contemporary empirical literature on direct-to-consumer (DTC) telemedicine services within primary care. MEDLINE, Embase and SCOPUS were strategically searched and screened. Data on the modality of consultations, population of focus, condition of focus andtreatment of focus were extracted, narratively synthesised and tabulated. Forty-four articles were included in this review. Most used quantitative methods, with predominantly cross-sectional or retrospective cohort designs. DTC telemedicine user characteristics and perspectives were most researched, followed by quality and safety. Most services used video or text messaging. Articles typically examined a specific health condition (eg acute respiratory infections) and its treatment, and several focused on a specific population (eg men). In light of the poor evidence base and lack of rigorous studies, there is a critical need for more robust research on DTC telemedicine within primary care. Quality assessment tool development and health economics analyses are necessary to support the integratation of DTC telemedicine services with traditional primary care systems and improve primary healthcare quality and efficiency.

Estimating Utility Values for Health States of Nigerian Individuals with Stroke or Epilepsy Using the SF-36: A Brief Report on the Results of a Cross-Sectional Survey.

We estimated a health state utility value for stroke and epilepsy to aid researchers and public health policy makers in conducting health economic analysis and outcomes research.

Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022.

Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China. Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran's Ianalysis. The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran's I <0) and percentage of urban population (Moran's I <0), and positively correlated with the number of pediatric beds per million population (Moran's I >0). The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.

P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort. Methods We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval &amp;lt;8 weeks and/or dosing &amp;gt;5mg/kg. We examined IBD outcomes prior to and 12 months post DE. Results A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml). Faecal calprotectin (FCP) remission rate (FCP &amp;lt;250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p&amp;lt;0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p&amp;lt;0.001) and radiological investigations (243 vs 343; p&amp;lt;0.001). Conclusion Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort

PurposeGenome sequencing (GS)–specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)–negative intellectual disability (ID) cohorts have not been reported extensively. MethodsES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. ResultsThe ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis. ConclusionPerforming GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost.

Multimorbidity-associated emergency hospital admissions: a "screen and link" strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol.

The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub-Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng'ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.