Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against.

Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence 'for' and 'against' the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team.

Drug use and spending under a formulary informed by cost-effectiveness.

BACKGROUND: The National Academy of Medicine has called for value-based drug formularies to address health plan prescription drug spending while maintaining access to high-value medicines. Thirty employer-sponsored plans implemented a "Value-Based Formulary-essentials" (VBF-e) program that uses cost-effectiveness evidence to inform cost-sharing and coverage exclusion. OBJECTIVE: To evaluate if the VBF-e was associated with changes in medication use and patient out-of-pocket spending and health plan spending on prescription drugs and other health care. METHODS: This was a cohort study using a difference-in-differences design from 2015 through 2019 with 1 year of follow-up after VBF-e implementation at Premera Blue Cross, the largest nonprofit health plan in the Pacific Northwest. The VBF-e exposure group was composed of all individuals aged younger than 65 years and enrolled at least 12 months prior to their employer group's VBF-e implementation date. The contemporaneous control group was composed of propensity score-matched individuals with the same inclusion criteria but their employer group that did not implement VBF-e. We prespecified the following outcomes: days of medication on hand overall and by VBF-e tier (high-value generic, brand, and specialty drugs were in tiers 1 to 3, respectively, and low-value drugs were in tier 4 or excluded from coverage); prescription drug spending; and other health care use (emergency department visits, hospital days, and outpatient visits). RESULTS: Comparing 12,111 exposed (mean age = 36.0; 49.8% female sex) participants with 24,222 control participants (mean age = 34.7; 49.6% female sex), VBF-e reduced use of low-value drugs by 0.3 days per member per month (PMPM) (95% CI = -0.5 to -0.1; 17% decrease) for tier 4 drugs and 0.4 days PMPM (95% CI = -0.5 to -0.4; 83% decrease) for excluded drugs. High-value specialty drug use increased by 0.1 days PMPM (95% CI = 0.0-0.1; 123% increase). Health plan spending decreased by $14 PMPM (95% CI = -26 to -4) and member out-of-pocket spending increased by $1 PMPM (95% CI = 1-2). Other health care use did not change significantly. CONCLUSIONS: An exclusion formulary informed by cost-effectiveness evidence reduced low-value drug use, increased high-value specialty drug use, reduced health plan spending, and increased member out-of-pocket spending without increasing acute care use. DISCLOSURES: This research was supported by a grant from the Patrick and Catherine Weldon Donaghue Medical Research Foundation's Greater Value Portfolio Program. Study Registration Number: NCT04904055.

Methodology for conducting a comprehensive product review in managed care.

The high degree of complexity of the product-review process and differences in procedures between organizations have resulted in a need for best practices and an overall product-review process to create efficiencies for health care decision makers. In an effort to streamline product-review concepts, this article outlines the different components of the review process, including clinical and economic review, formulary placement determination, and evaluation of alternatives within a drug class. The article also details opportunities for the near future, as technology continues to advance and alignment between medical and pharmacy benefits is desired. DISCLOSURES: Drs Linnerooth, Penley, Ha, and Craven report employment with Xcenda, which provided funding for the manuscript. Drs Sauvageau and Hydery report employment Xcenda, which provided funding for the manuscript, and stock holdings with AmerisourceBergen. Dr Feeney reports support for attending meetings and/or travel provided by Highmark, Inc. Dr Thomas reports receipt of consulting fees from ActiveRADAR, board member roles with ActiveRADAR and RoundtableRx, an adjunct professor role with the University of Minnesota, and stock options and pensions with Eli Lilly and Aetna/CVS. Dr Watkins reports payment or honoraria from ISPOR and for articles written for Value and Outcomes Spotlight, and support for attending meetings and/or travel by AMCP.

Aspirin and cancer: biological mechanisms and clinical outcomes.

Evidence on aspirin and cancer comes from two main sources: (1) the effect of aspirin upon biological mechanisms in cancer, and (2) clinical studies of patients with cancer, some of whom take aspirin. A series of systematic literature searches identified published reports relevant to these two sources. The effects of aspirin upon biological mechanisms involved in cancer initiation and growth appear to generate reasonable expectations of effects upon the progress and mortality of cancer. Clinical evidence on aspirin appears overall to be favourable to the use of aspirin, but evidence from randomized trials is limited, and inconsistent. The main body of evidence comes from meta-analyses of observational studies of patients with a wide range of cancers, about 25% of whom were taking aspirin. Heterogeneity is large but, overall, aspirin is associated with increases in survival and reductions in metastatic spread and vascular complications of different cancers. It is important that evaluations of aspirin used as an adjunct cancer treatment are based upon all the available relevant evidence, and there appears to be a marked harmony between the effects of aspirin upon biological mechanisms and upon the clinical progress of cancer.

Challenges of Health Technology Assessment in Pluralistic Healthcare Systems: An ISPOR Council Report.

Health technology assessment (HTA) has been growing in use over the past 40 years, especially in its impact on decisions regarding the reimbursement, adoption, and use of new drugs, devices, and procedures. In countries or jurisdictions with "pluralistic" healthcare systems, there are multiple payers or sectors, each of which could potentially benefit from HTA. Nevertheless, a single HTA, conducted centrally, may not meet the needs of these different actors, who may have different budgets, current standards of care, populations to serve, or decision-making processes. This article reports on the research conducted by an ISPOR Health Technology Assessment Council Working Group established to examine the specific challenges of conducting and using HTA in countries with pluralistic healthcare systems. The Group used its own knowledge and expertise, supplemented by a narrative literature review and survey of US payers, to identify existing challenges and any initiatives taken to address them. We recommend that countries with pluralistic healthcare systems establish a national focus for HTA, develop a uniform set of HTA methods guidelines, ensure that HTAs are produced in a timely fashion, facilitate the use of HTA in the local setting, and develop a framework to encourage transparency in HTA. These efforts can be enhanced by the development of good practice guidance from ISPOR or similar groups and increased training to facilitate local use of HTA.

National influenza surveillance systems in five European countries: a qualitative comparative framework based on WHO guidance.

BACKGROUND: Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance. METHODS: Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries. RESULTS: France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data. CONCLUSIONS: This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases.

The evolving role of weather types on rainfall chemistry under large reductions in pollutant emissions.

Long-term change and shorter-term variability in the atmospheric deposition of pollutants and marine salts can have major effects on the biogeochemistry and ecology of soils and surface water ecosystems. In the 1980s, at the time of peak acid deposition in the UK, deposition loads were highly dependent on prevailing weather types, and it was postulated that future pollution recovery trajectories would be partly dependent on any climate change-driven shifts in weather systems. Following three decades of substantial acidic emission reductions, we used monitoring data collected between 1992 and 2015 from four UK Environmental Change Network (ECN) sites in contrasting parts of Great Britain to examine the trends in precipitation chemistry in relation to prevailing weather conditions. Weather systems were classified on the basis of Lamb weather type (LWT) groupings, while emissions inventories and clustering of air mass trajectories were used to interpret the observed patterns. Concentrations of ions showed clear differences between cyclonic-westerly-dominated periods and others, reflecting higher marine and lower anthropogenic contributions in Atlantic air masses. Westerlies were associated with higher rainfall, higher sea salt concentrations, and lower pollutant concentrations at all sites, while air mass paths exerted additional controls. Westerlies therefore have continued to favour higher sea salt fluxes, whereas emission reductions are increasingly leading to positive correlations between westerlies and pollutant fluxes. Our results also suggest a shift from the influence of anthropogenic emissions to natural emissions (e.g., sea salt) and climate forcing as they are transported under relatively cleaner conditions to the UK. Westerlies have been relatively frequent over the ECN monitoring period, but longer-term cyclicity in these weather types suggests that current contributions to precipitation may not be sustained over coming years.

A comparison of coronavirus disease 2019 and seasonal influenza surveillance in five European countries: France, Germany, Italy, Spain and the United Kingdom.

BACKGROUND: In response to the coronavirus disease (COVID-19) outbreak that unfolded across Europe in 2020, the World Health Organisation (WHO) called for repurposing existing influenza surveillance systems to monitor COVID-19. This analysis aimed to compare descriptively the extent to which influenza surveillance systems were adapted and enhanced and how COVID-19 surveillance could ultimately benefit or disrupt routine influenza surveillance. METHODS: We used a previously developed framework in France, Germany, Italy, Spain and the United Kingdom to describe COVID-19 surveillance and its impact on influenza surveillance. The framework divides surveillance systems into seven subsystems and 20 comparable outcomes of interest and uses five evaluation criteria based on WHO guidance. Information on influenza and COVID-19 surveillance systems were collected from publicly available resources shared by European and national public health agencies. RESULTS: Overall, non-medically attended, virological, primary care and mortality surveillance were adapted in most countries to monitor COVID-19, although community, outbreak and hospital surveillance were reinforced in all countries. Data granularity improved, with more detailed demographic and medical information recorded. A shift to systematic notification for cases and deaths enhanced both geographic and population representativeness, although the sampling strategy benefited from the roll out of widespread molecular testing. Data communication was greatly enhanced, contributing to improved public awareness. CONCLUSIONS: Well-established influenza surveillance systems are a key component of pandemic preparedness, and their upgrade allowed European countries to respond to the COVID-19 pandemic. However, uncertainties remain on how both influenza and COVID-19 surveillance can be jointly and durably implemented.

Parkland Trauma Index of Mortality: Real-Time Predictive Model for Trauma Patients.

OBJECTIVE: Vital signs and laboratory values are used to guide decisions to use damage control techniques in lieu of early definitive fracture fixation. Previous models attempted to predict mortality risk but have limited utility. There is a need for a dynamic model that captures evolving physiologic changes during a trauma patient's hospital course. METHODS: The Parkland Trauma Index of Mortality (PTIM) is a machine learning algorithm that uses electronic medical record data to predict mortality within 48 hours during the first 3 days of hospitalization. It updates every hour, recalculating as physiology changes. The model was developed using 1935 trauma patient encounters from 2009 to 2014 and validated on 516 patient encounters from 2015 to 2016. Model performance was evaluated statistically. Data were collected retrospectively on its performance after 1 year of clinical use. RESULTS: In the validation data set, PTIM accurately predicted 52 of the sixty-three 12-hour time intervals within 48 hours of mortality, for sensitivity of 82.5% [95% confidence interval (CI), 73.1%-91.9%]. The specificity was 93.6% (95% CI, 92.5%-94.8%), and the positive predictive value (PPV) was 32.5% (95% CI, 25.2%-39.7%). PTIM predicted survival for 1608 time intervals and was incorrect only 11 times, yielding a negative predictive value of 99.3% (95% CI, 98.9%-99.7%). The area under the curve of the receiver operating characteristic curve was 0.94.During the first year of clinical use, when used in 776 patients, the last PTIM score accurately predicted 20 of the twenty-three 12-hour time intervals within 48 hours of mortality, for sensitivity of 86.9% (95% CI, 73%-100%). The specificity was 94.7% (95% CI, 93%-96%), and the positive predictive value was 33.3% (95% CI, 21.4%-45%). The model predicted survival for 716 time intervals and was incorrect 3 times, yielding a negative predictive value of 99.6% (95% CI, 99.1%-100%). The area under the curve of the receiver operating characteristic curve was 0.97. CONCLUSIONS: By adapting with the patient's physiologic response to trauma and relying on electronic medical record data alone, the PTIM overcomes many of the limitations of previous models. It may help inform decision-making for trauma patients early in their hospitalization. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers.

BACKGROUND: Despite the accumulation of research papers on aspirin and cancer, there is doubt as to whether or not aspirin is an acceptable and effective adjunct treatment of cancer. The results of several randomised trials are awaited, and these should give clear evidence on three common cancers: colon, breast and prostate. The biological effects of aspirin appear likely however to be of relevance to cancer generally, and to metastatic spread, rather than just to one or a few cancers, and there is already a lot of evidence, mainly from observational studies, on the association between aspirin and survival in a wide range of cancers. AIMS: In order to test the hypothesis that aspirin taking is associated with an increase in the survival of patients with cancer, we conducted a series of systematic literature searches to identify clinical studies of patients with cancer, some of whom took aspirin after having received a diagnosis of cancer. RESULTS: Three literature searches identified 118 published observational studies in patients with 18 different cancers. Eighty-one studies report on aspirin and cancer mortality and 63 studies report on all-cause mortality. Within a total of about a quarter of a million patients with cancer who reported taking aspirin, representing 20%-25% of the total cohort, we found aspirin to be associated with a reduction of about 20% in cancer deaths (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84 in 70 reports and a pooled odds ratio (OR): 0.67; 0.45, 1.00 in 11 reports) with similar reductions in all-cause mortality (HR: 0.80; 0.74, 0.86 in 56 studies and OR: 0.57; 0.36, 0.89 in seven studies). The relative safety of aspirin taking was examined in the studies and the corresponding author of every paper was written to asking for additional information on bleeding. As expected, the frequency of bleeding increased in the patients taking aspirin, but fatal bleeding was rare and no author reported a significant excess in fatal bleeds associated with aspirin. No author mentioned cerebral bleeding in the patients they had followed. CONCLUSIONS: There is a considerable body of evidence suggestive of about a 20% reduction in mortality in patients with cancer who take aspirin, and the benefit appears not to be restricted to one or a few cancers. Aspirin, therefore, appears to deserve serious consideration as an adjuvant treatment of cancer, and patients with cancer, and their carers, have a right to be informed of the available evidence.

A solution scan of societal options to reduce transmission and spread of respiratory viruses: SARS-CoV-2 as a case study.

Societal biosecurity - measures built into everyday society to minimize risks from pests and diseases - is an important aspect of managing epidemics and pandemics. We aimed to identify societal options for reducing the transmission and spread of respiratory viruses. We used SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as a case study to meet the immediate need to manage the COVID-19 pandemic and eventually transition to more normal societal conditions, and to catalog options for managing similar pandemics in the future. We used a 'solution scanning' approach. We read the literature; consulted psychology, public health, medical, and solution scanning experts; crowd-sourced options using social media; and collated comments on a preprint. Here, we present a list of 519 possible measures to reduce SARS-CoV-2 transmission and spread. We provide a long list of options for policymakers and businesses to consider when designing biosecurity plans to combat SARS-CoV-2 and similar pathogens in the future. We also developed an online application to help with this process. We encourage testing of actions, documentation of outcomes, revisions to the current list, and the addition of further options.

The Role of Digital Technologies in Responding to the Grand Challenges of the Natural Environment: The Windermere Accord.

Digital technology is having a major impact on many areas of society, and there is equal opportunity for impact on science. This is particularly true in the environmental sciences as we seek to understand the complexities of the natural environment under climate change. This perspective presents the outcomes of a summit in this area, a unique cross-disciplinary gathering bringing together environmental scientists, data scientists, computer scientists, social scientists, and representatives of the creative arts. The key output of this workshop is an agreed vision in the form of a framework and associated roadmap, captured in the Windermere Accord. This accord envisions a new kind of environmental science underpinned by unprecedented amounts of data, with technological advances leading to breakthroughs in taming uncertainty and complexity, and also supporting openness, transparency, and reproducibility in science. The perspective also includes a call to build an international community working in this important area.

Positive Psychological Change Following a Cancer Diagnosis in Old Age: A Mixed-Methods Study.

BACKGROUND: Despite the stress inherent in a cancer diagnosis, many cancer survivors report benefits, including perceptions of personal growth and well-being. Among adults 60 years or older, for whom cancer diagnoses are most prevalent, there is a notable lack of research on positive psychological change. OBJECTIVE: This mixed-methods study was designed to advance current understanding of positive psychology (ie, posttraumatic growth, well-being) in older adults with cancer. METHODS: Fifty-six older adult cancer survivors were recruited through a statewide cancer registry and the community. Participants completed questionnaires on posttraumatic growth, well-being, coping, and quality of life, as well as a series of open-ended questions via mail. RESULTS: Participants reported high posttraumatic growth and well-being and primarily adaptive and emotion-focused coping strategies. They also reported better mental quality of life (P = .0001) but not physical quality of life (P = .31) compared with age-adjusted population norms. Older age was associated with less posttraumatic growth (r = -0.32, P = .02) but not well-being (P = .34). Qualitative responses emphasized appreciation and acceptance and a reliance on faith and social support and provided context for quantitative results. CONCLUSIONS: This mixed-methods study suggests that older adults report positive psychological change and adaptive coping with cancer, demonstrating their high level of emotional resilience. IMPLICATIONS FOR PRACTICE: Mental health screenings should be provided as appropriate, but oncology nurses should also consider the potential for positive psychological change postdiagnosis. The provision of care and social support may need to be modified to accommodate older cancer survivors' needs.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Tackling the Challenges of 21st-Century Open Science and Beyond: A Data Science Lab Approach.

In recent years, there has been a drive toward more open, cross-disciplinary science taking center stage. This has presented a number of challenges, including providing research platforms for collaborating scientists to explore big data, develop methods, and disseminate their results to stakeholders and decision makers. We present our vision of a "data science lab" as a collaborative space where scientists (from different disciplines), stakeholders, and policy makers can create data-driven solutions to environmental science's grand challenges. We set out a clear and defined research roadmap to serve as a focal point for an international research community progressing toward a more data-driven and transparent approach to environmental data science, centered on data science labs. This includes ongoing case studies of good practice, with the infrastructural and methodological developments required to enable data science labs to support significant increase in our cross- and trans-disciplinary science capabilities.

The use of 5-aminosalicylates in Crohn's disease: a retrospective study using the UK Clinical Practice Research Datalink.

BACKGROUND: There are few recent studies on the use of 5-aminosalicylates (5-ASA) as therapy for Crohn's disease (CD) in routine clinical practice. The aim of this database investigation was to provide real-world evidence on 5-ASA use in CD. METHODS: Patients with CD, aged ≥18 years when first prescribed 5-ASA (index date) and having received 5-ASA at any time between 01 January 2006 and 07 May 2018, were included for analysis. Outcomes included treatment patterns and resource use. RESULTS: Of 21,456 patients with CD, 9492 (44.2%) had been prescribed 5-ASA, with the majority (5606; 59.1%) starting on oral 5-ASA as monotherapy. 58.3% (5537) of patients on 5-ASA did not require dose change, 67.6% (6416) did not require supplementary treatment (e.g., corticosteroids, immunosuppressants, etc.), and 4.6% (436) required a switch to another treatment. Resource use was significantly decreased in the year after vs. year before 5-ASA initiation (including: specialist referrals, hospitalizations and hospital days; all P<0.001). Patients remained on 5-ASA for a median of 4.7 years (interquartile range 1.2-10.1). 25.3% (2406) of patients were still on 5-ASA at 10 years. There was a significant correlation between earlier use of 5-ASA following diagnosis and longer 5-ASA retention (P<0.001). CONCLUSIONS: 5-ASA is widely used as a long-term treatment for CD, as evidenced by continuation rates extending beyond 10 years in a quarter of patients. CD-related healthcare resource use decreased significantly in the year following 5-ASA initiation. Earlier use was associated with longer retention.

ICER's Version of HTA Is Positioned to Guide U.S. Health Care Reform.

DISCLOSURES: No funding supported the writing of this letter. The author is an unpaid member of the ICER Methods Advisory Committee and has participated in discussions at ICER meetings and meetings of the New England Comparative Effectiveness Advisory Council (CEPAC).

Resource use and direct medical costs of acute respiratory illness in the UK based on linked primary and secondary care records from 2001 to 2009.

BACKGROUND: Previous studies have shown that influenza is associated with a substantial healthcare burden in the United Kingdom (UK), but more studies are needed to evaluate the resource use and direct medical costs of influenza in primary care and secondary care. METHODS: A retrospective observational database study in the UK to describe the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI), according to age, and risk status (NCT Number: 01521416). Patients with influenza, ARI or influenza-related respiratory infections during 9 consecutive pre-pandemic influenza peak seasons were identified by READ codes in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset. The study period was from 21st January 2001 to 31st March 2009. RESULTS: A total of 156,193 patients had ≥1 general practitioner (GP) episode of ARI, and a total of 82,204 patients received ≥1 GP prescription, at a mean of 2.5 (standard deviation [SD]: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions equated to £462,827 per year per 100,000 patients. The yearly cost of prescribed medication for ARI was £319,732, at an estimated cost of £11,596,350 per year extrapolated to the UK, with 40% attributable to antibiotics. The mean cost of hospital admissions equated to a yearly cost of £981,808 per 100,000 patients. The total mean direct medical cost of ARI over 9 influenza seasons was £21,343,445 (SD: £10,441,364), at £136.65 (SD: £66.85) per case. CONCLUSIONS: Extrapolating to the UK population, for pre-pandemic influenza seasons from 2001 to 2009, the direct medical cost of ARI equated to £86 million each year. More studies are needed to assess the costs of influenza disease to help guide public health decision-making for seasonal influenza in the UK.