Treatment Effect Waning Assumptions: A Review of National Institute of Health and Care Excellence Technology Appraisals.

OBJECTIVES: This study aims to review the National Institute of Health and Care Excellence (NICE) technology assessments to gain insights into the implementation of treatment effect (TE) waning, whereby the hazard or survival in an assessed technology converges to that of the comparator. This analysis aims to contribute to inform future guidance in this area. METHODS: Technology appraisals published October 20, 2021 to September 20, 2023 were reviewed and data extracted on TE waning circumstances, methods, and rationale to compile a database based on 3 research questions: When are TE waning assumptions used? What methods are used? Why have the company/Evidence Assessment Group/committee preferred these methods? RESULTS: Both the evidence assessment group/company and the committee included TE waning assumptions in 28 appraisals. There was no pattern of waning assumptions between shorter (<20 years) and longer (>20 years) time horizons. The most prominent time point for applying waning assumptions was at 5 years, with 30 out of 59 (50.8%) of the methods applied used 5 years. Stopping rules were used in 21 out of 30 (70.1%) of the appraisals for which the committee included waning, and waning assumptions were used more in oncology. The most common reason given for including TE waning assumptions was precedent from prior appraisals. CONCLUSIONS: Considerable heterogeneity existed in both the methods used and justifications given for TE waning assumptions. This variability poses a risk of inconsistent decision making. Reliance on past appraisals emphasizes the necessity to advocate for evidence-driven approaches and underscores the demand for guidance on suitable methods for incorporating assumptions.

On Orthorexia Nervosa: A Systematic Review of Reviews.

INTRODUCTION: Orthorexia nervosa (ON), characterized by a pathological preoccupation with "extreme dietary purity," is increasingly observed as a mental health condition among young adults and the general population. However, its diagnosis is not formally recognized and has remained contentious. OBJECTIVE: In this systematic review, we attempt to overview previous reviews on ON, focusing on the methodological and conceptual issues with ON. This would serve both as a summary and a way to highlight gaps in earlier research. METHODS: This systematic review took reference from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines, and using combinations of the search terms ("orthorexia" OR "orthorexia nervosa" OR "ON") AND ("review" OR "systematic review" OR "meta-analysis"), a literature search was performed on EMBASE, Medline and PsycINFO databases from inception up to October 31, 2023. Articles were included if (1) they were written or translated into English and (2) contained information pertaining to the diagnostic stability or validity of ON, or instruments used to measure ON symptoms and behaviors. Only review articles with a systematic literature search approach were included. RESULTS: A total of 22 reviews were qualitatively reviewed. Several studies have reported variable prevalence of ON and highlighted the lack of thoroughly evaluated measures of ON with clear psychometric properties, with no reliable estimates. ORTO-15 and its variations such as ORTO-11, ORTO-12 are popularly used, although their use is discouraged. Existing instruments lack specificity for pathology and several disagreements on the conceptualization and hence diagnostic criteria of ON exist. DISCUSSION: Previous reviews have consistently highlighted the highly variable (and contradictory) prevalence rates with different instruments to measure ON, lack of stable factor structure and psychometrics across ON measures, paucity of data on ON in clinical samples, and a need for a modern re-conceptualization of ON. The diagnosis of ON is challenging as it likely spans a spectrum from "normal" to "abnormal," and "functional" to "dysfunctional." "Non-pathological" orthorexia is not related to psychopathological constructs in the same way that ON is.

Modelling Treatment Sequences in Immunology: Optimizing Patient Outcomes.

INTRODUCTION: For some immune-mediated disorders, despite the range of therapies available there is limited evidence on which treatment sequences are best for patients and healthcare systems. We investigated how their selection can impact outcomes in an Italian setting. METHODS: A 3-year state-transition treatment-sequencing model calculated potential effectiveness improvements and budget reallocation considerations associated with implementing optimal sequences in ankylosing spondylitis (AS), Crohn's disease (CD), non-radiographic axial spondyloarthritis (NR-AxSpA), plaque psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ulcerative colitis (UC). Sequences included three biological or disease-modifying treatments, followed by best supportive care. Disease-specific response measures were selected on the basis of clinical relevance, data availability, and data quality. Efficacy was differentiated between biologic-naïve and experienced populations, where possible, using published network meta-analyses and real-world data. All possible treatment sequences, based on reimbursement as of December 2022 in Italy (analyses' base country), were simulated. RESULTS: Sequences with the best outcomes consistently employed the most efficacious therapies earlier in the treatment pathway. Improvements to prescribing practice are possible in all diseases; however, most notable was UC, where the per-patient 3-year average treatment failure was 37.3% higher than optimal. The results focused on the three most crowded and prevalent immunological sub-condition diseases in dermatology, rheumatology, and gastroenterology: PsO, RA, and UC, respectively. By prescribing from within the top 20% of the most efficacious sequences, the model found a 15.1% reduction in treatment failures, with a 1.59% increase in drug costs. CONCLUSIONS: Prescribing more efficacious treatments earlier provides a greater opportunity to improve patient outcomes and minimizes treatment failures.

A Cost-Utility Analysis of Add-On Cannabidiol Versus Usual Care Alone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex in England and Wales.

OBJECTIVES: The aim of this study was to evaluate the cost effectiveness of plant-derived highly purified cannabidiol (Epidyolex® in the UK; 100 mg/mL oral solution) as an add-on treatment to usual care for the management of treatment-refractory seizures associated with tuberous sclerosis complex (TSC) in patients aged ≥ 2 years. METHODS: A cohort-based model was developed using a National Health Service perspective and lifetime horizon. Health states were based on weekly seizure frequency and seizure-free days, utilizing patient-level data from the GWPCARE6 trial (ClinicalTrials.gov identifier: NCT02544763). Two independent regression models were applied to individual patient-level data to predict seizure-free days and seizure frequency. Healthcare resource utilization data were sourced from a Delphi panel, and patient and caregiver health-related quality of life values were elicited using vignettes valued by the general public. Outcomes relating to TSC-associated neuropsychiatric disorders were modeled with costs and quality-adjusted life-years sourced from published literature. RESULTS: In the base case, compared with usual care alone, 12 mg/kg/day cannabidiol was associated with an incremental cost-effectiveness ratio (ICER) of £23,797. The National Institute for Health and Care Excellence disease severity modifier reduced the ICER to £19,831. Probabilities of cost effectiveness at willingness-to-pay thresholds of £20,000 and £30,000 were 30% and 52%, respectively, for the base case and 39% and 66%, respectively, for the disease severity modifier. Results were robust to sensitivity and scenario analyses. CONCLUSIONS: At 12 mg/kg/day and an ICER threshold of £20,000-£30,000, we provide evidence for the cost effectiveness of add-on cannabidiol treatment for patients with TSC-associated seizures aged ≥ 2 years who are refractory to current treatment.

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study.

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD) from 2010 to 2020. We fitted generalized structural equation models, calculating hazard ratios (HRs) using a Weibull model. We constructed Kaplan-Meier survival curves and calculated the predicted marginal probability for each SHI category. Results: We included 659 cases. In both univariable and multivariable analyses, SHI did not have a significant association with survival. Indirect pathways of SHI mediated through covariates such as Emergency Medical Services (EMS) response time (HR of low-medium, high-medium and high SHI when compared to low SHI: 0.98 (0.88-1.10), 1.01 (0.93-1.11), 1.02 (0.93-1.12) respectively), and age of arrest (HR of low-medium, high-medium and high SHI when compared to low SHI: 1.02 (0.75-1.38), 1.08 (0.84-1.38), 1.18 (0.91-1.54) respectively) had no significant association with OHCA survival. There was no clear trend in the predicted marginal probability of survival among the different SHI categories. Conclusions: We did not find a significant association between SES and OHCA survival outcomes in residential areas in Singapore. Among other reasons, this could be due to affordable healthcare across different socioeconomic classes.

Endothelial periostin regulates vascular remodeling by promoting endothelial dysfunction in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with extracellular matrix (ECM) deposition, vascular cell hyperproliferation, and neointima formation in the small pulmonary artery. Endothelial dysfunction is considered a key feature in the initiation of vascular remodeling. Although vasodilators have been used for the treatment of PAH, it remains a life-threatening disease. Therefore, it is necessary to identify novel therapeutic targets for PAH treatment. Periostin (POSTN) is a secretory ECM protein involved in physiological and pathological processes, such as tissue remodeling, cell adhesion, migration, and proliferation. Although POSTN has been proposed as a potential target for PAH treatment, its role in endothelial cells has not been fully elucidated. Here, we demonstrated that POSTN upregulation correlates with PAH by analyzing a public microarray conducted on the lung tissues of patients with PAH and biological experimental results from in vivo and in vitro models. Moreover, POSTN overexpression leads to ECM deposition and endothelial abnormalities such as migration. We found that PAH-associated endothelial dysfunction is mediated at least in part by the interaction between POSTN and integrin-linked protein kinase (ILK), followed by activation of nuclear factor-κB signaling. Silencing POSTN or ILK decreases PAH-related stimuli-induced ECM accumulation and attenuates endothelial abnormalities. In conclusion, our study suggests that POSTN serves as a critical regulator of PAH by regulating vascular remodeling, and targeting its role as a potential therapeutic strategy for PAH.

Examining Public Messaging on Influenza Vaccine over Social Media: Unsupervised Deep Learning of 235,261 Twitter Posts from 2017 to 2023.

Although influenza vaccines are safe and efficacious, vaccination rates have remained low globally. Today, with the advent of new media, many individuals turn to social media for personal health questions and information. However, misinformation may be rife, and health communications may be suboptimal. This study, therefore, aimed to investigate the public messaging related to influenza vaccines by organizations over Twitter, which may have a far-reaching influence. The theoretical framework of the COM-B (capacity, opportunity, and motivation component of behavior) model was used to interpret the findings to aid the design of messaging strategies. Employing search terms such as "flu jab", "flu vaccine", "influenza vaccine", and '" influenza jab", tweets posted in English and by organizations from 1 January 2017 to 1 March 2023 were extracted and analyzed. Using topic modeling, a total of 235,261 tweets by organizations over Twitter were grouped into four main topics: publicizing campaigns to encourage influenza vaccination, public education on the safety of influenza vaccine during pregnancy, public education on the appropriate age to receive influenza vaccine, and public education on the importance of influenza vaccine during pregnancy. Although there were no glaring pieces of misinformation or misconceptions, the current public messaging covered a rather limited scope. Further information could be provided about influenza and the benefits of vaccination (capability), promoting community, pharmacist-led influenza vaccination, and other avenues (opportunity), and providing greater incentivization and support for vaccination (motivation).

Performance of the ROX index in predicting high flow nasal cannula failure in COVID-19 patients: a systematic review and meta-analysis.

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.

Examining the Negative Sentiments Related to Influenza Vaccination from 2017 to 2022: An Unsupervised Deep Learning Analysis of 261,613 Twitter Posts.

Several countries are witnessing significant increases in influenza cases and severity. Despite the availability, effectiveness and safety of influenza vaccination, vaccination coverage remains suboptimal globally. In this study, we examined the prevailing negative sentiments related to influenza vaccination via a deep learning analysis of public Twitter posts over the past five years. We extracted original tweets containing the terms 'flu jab', '#flujab', 'flu vaccine', '#fluvaccine', 'influenza vaccine', '#influenzavaccine', 'influenza jab', or '#influenzajab', and posted in English from 1 January 2017 to 1 November 2022. We then identified tweets with negative sentiment from individuals, and this was followed by topic modelling using machine learning models and qualitative thematic analysis performed independently by the study investigators. A total of 261,613 tweets were analyzed. Topic modelling and thematic analysis produced five topics grouped under two major themes: (1) criticisms of governmental policies related to influenza vaccination and (2) misinformation related to influenza vaccination. A significant majority of the tweets were centered around perceived influenza vaccine mandates or coercion to vaccinate. Our analysis of temporal trends also showed an increase in the prevalence of negative sentiments related to influenza vaccination from the year 2020 onwards, which possibly coincides with misinformation related to COVID-19 policies and vaccination. There was a typology of misperceptions and misinformation underlying the negative sentiments related to influenza vaccination. Public health communications should be mindful of these findings.

Examining the Public Messaging on 'Loneliness' over Social Media: An Unsupervised Machine Learning Analysis of Twitter Posts over the Past Decade.

Loneliness is an issue of public health significance. Longitudinal studies indicate that feelings of loneliness are prevalent and were exacerbated by the Coronavirus Disease 2019 (COVID-19) pandemic. With the advent of new media, more people are turning to social media platforms such as Twitter and Reddit as well as online forums, e.g., loneliness forums, to seek advice and solace regarding their health and well-being. The present study therefore aimed to investigate the public messaging on loneliness via an unsupervised machine learning analysis of posts made by organisations on Twitter. We specifically examined tweets put out by organisations (companies, agencies or common interest groups) as the public may view them as more credible information as opposed to individual opinions. A total of 68,345 unique tweets in English were posted by organisations on Twitter from 1 January 2012 to 1 September 2022. These tweets were extracted and analysed using unsupervised machine learning approaches. BERTopic, a topic modelling technique that leverages state-of-the-art natural language processing, was applied to generate interpretable topics around the public messaging of loneliness and highlight the key words in the topic descriptions. The topics and topic labels were then reviewed independently by all study investigators for thematic analysis. Four key themes were uncovered, namely, the experience of loneliness, people who experience loneliness, what exacerbates loneliness and what could alleviate loneliness. Notably, a significant proportion of the tweets centred on the impact of the COVID-19 pandemic on loneliness. While current online interactions are largely descriptive of the complex and multifaceted problem of loneliness, more targeted prosocial messaging appears to be lacking to combat the causes of loneliness brought up in public messaging.

Dynamic Mortality Modeling: Incorporating Predictions of Future General Population Mortality Into Cost-Effectiveness Analysis.

OBJECTIVES: Health economic models commonly apply observed general population mortality rates to simulate future deaths in a cohort. This is potentially problematic, because mortality statistics are records of the past, not predictions for the future. We propose a new dynamic general population mortality modeling approach, which enables analysts to implement predictions of future changes in mortality rates. The potential implications of moving from a conventional static approach to a dynamic approach are illustrated using a case study. METHODS: The model utilized in National Institute for Health and Care Excellence appraisal TA559, axicabtagene ciloleucel axi for diffuse large B-cell lymphoma, was replicated. National mortality projections were taken from the UK Office for National Statistics. Mortality rates by age and sex were updated each modeled year with the first modeled year using 2022 rates, the second modeled year 2023 and so on. A total of 4 different assumptions were made around age distribution: fixed mean age, lognormal, normal, and gamma. The dynamic model outcomes were compared with those from a conventional static approach. RESULTS: Including dynamic calculations increased the undiscounted life-years attributed to general population mortality by 2.4 to 3.3 years. This led to an increase in discounted incremental life-years within the case study of 0.38 to 0.45 years (8.1%-8.9%), and a commensurate impact on the economically justifiable price of £14 456 to £17 097. CONCLUSIONS: The application of a dynamic approach is technically simple and has the potential to meaningfully affect estimates of cost-effectiveness analysis. Therefore, we call on health economists and health technology assessment bodies to move toward use of dynamic mortality modeling in future.

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review.

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics.

Public perception on 'healthy ageing' in the past decade: An unsupervised machine learning of 63,809 Twitter posts.

The World Health Organization (WHO) started the initiative on healthy ageing from 2016 to 2020, which has now continued into the United Nations (UN) Decade of Healthy Ageing 2021-2030. Research into healthy ageing and healthy ageing communities have emphasized that the concept of healthy ageing encompasses a plurality of views and has multiple dimensions. Anchored in a transdisciplinary approach, the present report thus aimed to investigate public perceptions of healthy ageing via a deep analysis of social media posts on Twitter. Original tweets, containing the terms "Healthy Ageing" OR "healthy aging" OR "healthyageing" OR "healthyaging", and posted in English between 1 January 2012 and 30 June 2022 were extracted. Bidirectional Encoder Representations from Transformers (BERT) Named Entity Recognition was applied to select for individual users. Topic modelling, specifically BERTopic was used to generate interpretable topics and descriptions pertaining to the concept of healthy ageing. Subsequently, manual thematic analysis was performed by the study investigators, with independent reviews of the topic labels and themes. A total of 63,809 unique tweets were analyzed and clustered semantically into 16 topics. The public perception of healthy ageing could be broadly grouped into three themes: (1) healthy diet and lifestyle, (2) maintaining normal bodily functions and (3) preventive care. While most perceptions dovetail WHO's definition, there are some points regarding skin appearances, beauty and aging that should be closely considered in the design of initiatives in the UN Decade of Healthy Ageing and beyond.

The Challenge for Orphan Drugs Remains: Three Case Studies Demonstrating the Impact of Changes to NICE Methods and Processes and Alternative Mechanisms to Value Orphan Products.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) is responsible for ensuring that patients in England and Wales can access clinically and cost-effective treatments. However, NICE's processes pose significant reimbursement challenges for treatments for rare diseases. While some orphan medicines have been appraised via the highly specialised technology route, most are appraised via the single technology appraisal programme, a route that is expected to be increasingly used given new more restrictive highly specialised technology criteria. This often results in delays to access owing to differences in applicable thresholds and the single technology appraisal approach being ill-equipped to deal with the inevitable decision uncertainty. NICE recently published their updated methods and process manual, which includes a new severity-of-disease modifier and an instruction to be more flexible when considering uncertainty in rare diseases. However, as the threshold gap between the single technology appraisal and highly specialised technology programmes remains, it is unlikely that these changes alone will address the problem. OBJECTIVE: We explored the potential impact of quality-adjusted life-year weights in decision making. METHODS: We explored the impact of NICE's new severity-of-disease modifier weighting and two alternative methods (the use of alternative quality-adjusted life-year weights and the fair rate of return), using three recent single technology appraisals of orphan medicines (caplacizumab, teduglutide and pirfenidone for mild idiopathic pulmonary fibrosis). RESULTS: Our results suggest NICE's severity-of-disease modifier would not have affected the recommendations. Using alternative methods, based upon achievement of an incremental cost-effectiveness ratio below standard thresholds, patients could have received access to caplacizumab approximately 5 months earlier, and the appraisals for teduglutide and pirfenidone would have resulted in a positive recommendation following appraisal consultation meeting 1 when neither of these products was available over 5 years from the initial submission. CONCLUSION: Ultimately, moving from a restrictive end-of-life modifier to one based on disease severity is a more equitable approach likely to benefit many therapies, including orphan products. However, NICE's single technology appraisal updates are unlikely to result in faster reimbursement of orphan medicines, nor will they address concerns around market access for orphan medicines in the UK.

Psychodynamic Psychiatry in Singapore.

The authors provide an overview of the history of psychiatric services and training in Singapore, and the more recent introduction of psychodynamic psychotherapy training for psychiatric residents. They describe the current state of psychodynamic psychiatry services in the public healthcare system, including efforts at fostering psychodynamic thinking in nonpsychiatric community partners via community mental health integrated care programs and activities such as Balint Groups. They discuss current challenges in psychodynamic practice, such as the impact of language and culture on the Singaporean individual's receptiveness to psychodynamic psychotherapy, as well as systemic challenges in funding and expanding psychodynamic services. They highlight future directions, including challenges and opportunities for the local psychodynamic community in Singapore.

Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States.

AIMS: Approximately, 4% of Stage IV colorectal cancers (CRC) are microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. Patients with metastatic MSI-H/dMMR CRC receiving conventional therapies experience lower response rates and tend to have worse overall survival compared with patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. Pembrolizumab received FDA approval in 2020 for first-line treatment of Stage IV MSI-H/dMMR CRC based on significantly longer progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab). This study evaluated the cost-effectiveness of pembrolizumab vs. SoC as per KEYNOTE-177 and other first-line treatments for MSI-H/dMMR CRC from a US healthcare system perspective. METHODS: A three-health-state partitioned-survival model was built using progression-free and overall survival data from KEYNOTE-177 and a network meta-analysis. Utilities were derived from KEYNOTE-177 EQ-5D-3L data. Drug acquisition, administration, AE, surgery, monitoring, subsequent treatment, and terminal care costs were included. Sensitivity and scenario analyses were performed, including utilizing a state-transition model structure and adopting a societal perspective. RESULTS: Over a lifetime time horizon, pembrolizumab and SoC were associated with total QALYs of 4.85 and 3.23, and total costs of $381,735 and $370,465, respectively, resulting in an ICER of $6,984 per QALY. QALY gains were mainly driven by extended survival with pembrolizumab. Pembrolizumab incurred higher drug acquisition costs relative to SoC but was cost-saving in terms of drug administration, AE, monitoring, subsequent treatment, and terminal care. Pembrolizumab dominated FOLFOX + panitumumab, FOLFOXIRI, and FOLFOXIRI + bevacizumab, and presented ICERs of $35,220 and $276 against XELOX and XELOX + bevacizumab. Results were robust to sensitivity and scenario analyses. CONCLUSION: Pembrolizumab is highly cost-effective for the first-line treatment of unresectable or metastatic MSI-H/dMMR CRC in the US at a willingness-to-pay threshold of $100,000/QALY.Key messagesPembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab:Increases survival due to delaying and preventing progression;Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events;Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; andReduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events.

Impact of insulin pump therapy on key parameters of diabetes management and diabetes related emotional distress in the first 12 months.

AIMS: To evaluate the effect of continuous subcutaneous insulin infusion (CSII) on glycaemic control, hypoglycaemia and emotional distress in adults with type 1 diabetes (T1D) during the first 12 months. METHODS: 47 patients were started on CSII as per NICE guidelines. Anthropometric, clinical and biochemical parameters, hypoglycaemia rates and emotional distress measured by Problem Areas in Diabetes questionnaires (PAID) were recorded at baseline and during follow up at 3-6 months and 6-12 months. RESULTS: Mean HbA1c dropped by 1.1% (11.8 mmol/mol; p < 0.0001) at 3-6 months and by 0.8% (8.6 mmol/mol; p = 0.008) at 6-12 months. Most patients had improved HbA1c between 6.5 and 8.5% (48-69 mmol/mol) during these follow ups (68.3% and 71.5% respectively). Frequency of hypoglycaemia reduced from 338.2 to 187.2 and 155.3 per 100 patient years during follow ups. Severe hypoglycaemia also decreased from 48.9 to 8.5 and 6.3 per 100 patient years respectively. PAID scores improved from 29.8 ± 18.5 to 17.2 ± 14.0 (p = 0.0002) at 3-6 months and to 12.8 ± 11.7 (p < 0.00001) at 6-12 months. Reduction in HbA1c, insulin dose and PAID scores was more significant in group with HbA1c > 8.5% (69 mmol/mol) at baseline whereas improvement in episodes of hypoglycaemia and severe hypoglycaemic was more in patients who had HbA1c ≤ 8.5% before commencement of CSII therapy. CONCLUSIONS: CSII therapy led to early improvement in glycaemic control, rates of hypoglycaemia and diabetes specific emotional distress. As beneficial effects are recorded within the first few months, CSII therapy should be started more proactively in T1D.

Lenalidomide as maintenance treatment for patients with multiple myeloma after autologous stem cell transplantation: A pharmaco-economic assessment.

OBJECTIVE: Autologous stem cell transplantation (ASCT) has improved progression-free survival (PFS) and overall survival in eligible patients with newly diagnosed multiple myeloma (NDMM); however, relapse occurs. Maintenance therapy with lenalidomide (Len-Mt) extends survival and delays relapse and the subsequent initiation of costly second-line regimens. Here, we report the cost-effectiveness of Len-Mt following ASCT from a Dutch healthcare service perspective. METHODS: A partitioned survival model was developed to assess the lifetime costs and benefits for patients with NDMM. Efficacy was taken from a pooled meta-analysis of clinical trial data. Costs and subsequent therapy data were taken from sources appropriate for the Dutch market. RESULTS: Lenalidomide produced a quality-adjusted life year gain of 2.46 and a life year gain of 2.79 vs no maintenance treatment. The cost of lenalidomide was partially offset by savings of EUR 77 462 in subsequent treatment costs. The incremental cost-effectiveness ratio of Len-Mt vs no maintenance treatment was EUR 30 143. Key model drivers included subsequent therapies, dosing schedule, and time horizon. CONCLUSION: Lenalidomide is cost-effective after ASCT vs no maintenance therapy in the Netherlands. By extending PFS, lenalidomide delays the cost burdens associated with relapse and subsequent treatment lines.