Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens.

BACKGROUND: Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient's genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies. OBJECTIVES: This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines. METHODS: After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings. RESULTS: The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders. CONCLUSIONS: Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.

Health of Asylees Compared to Refugees in the United States Using Domestic Medical Examination Data, 2014-2016: A Cross-Sectional Analysis.

BACKGROUND: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. METHODS: We conducted a retrospective cross-sectional analysis of domestic medical examination data from 9 US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C virus (HBV, HCV), and select sexually transmitted infections and parasites by refugee or asylee visa status. RESULTS: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (prevalence ratio [PR] = 0.8), hepatitis B (0.7), hepatitis C (0.5), and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. CONCLUSIONS: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention's Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination.

Long-Term Physical Health Outcomes of Resettled Refugee Populations in the United States: A Scoping Review.

Several studies describe the health of recently resettled refugee populations in the US beyond the first 8 months after arrival. This review summarizes the results of these studies. Scientific articles from five databases published from January 2008 to March 2019 were reviewed. Articles were included if study subjects included any of the top five US resettlement populations during 2008-2018 and if data described long-term physical health outcomes beyond the first 8 months after arrival in the US. Thirty-three studies met the inclusion criteria (1.5%). Refugee adults had higher odds of having a chronic disease compared with non-refugee immigrant adults, and an increased risk for diabetes compared with US-born controls. The most commonly reported chronic diseases among Iraqi, Somali, and Bhutanese refugee adults included diabetes and hypertension. Clinicians should consider screening and evaluating for chronic conditions in the early resettlement period. Further evaluations can build a more comprehensive, long-term health profile of resettled refugees to inform public health practice.

Evaluation of Endocan and Tumor Necrosis Factor-α as Inflammatory Biomarkers in Type 2 Diabetes and Periodontal Disease.

Purpose: Type 2 diabetes mellitus (type 2 DM) and periodontitis encompass vascular endothelial changes. Endocan, a marker of endothelial dysfunction, has not been previously evaluated in diabetic patients with periodontal disease. This study was designed to evaluate the levels of endocan and tumor necrosis factor-alpha (TNF-α) in chronic periodontitis (CP) subjects with type 2 DM before and after nonsurgical periodontal therapy (NSPT). Materials and Methods: This study included 75 subjects with varying degrees of CP. Group I-included 25 systemically healthy individuals with CP, and Groups II and III-included 25 CP patients each with type 2 DM under good control (hemoglobin A1c [HbA1c] <7%) and poor control (HbA1c >8%), respectively. Periodontal parameters were assessed, and gingival crevicular fluid collections were performed for all patients at baseline and again following three months of NSPT. Levels of endocan and TNF-α were assessed using enzyme-linked immunosorbent assay. Results: Endocan levels were elevated in CP subjects with type 2 DM at baseline. There was a significant reduction in the Endocan and HbA1c levels (p < 0.01) among all the groups after NSPT. Conclusion: Endocan may be used as a novel diagnostic marker for pateints with type 2 DM and CP and as a potential prognostic marker for monitoring improvement in periodontal and glycemic status during NSPT.

Evaluation of a Program to Improve Linkage to and Retention in Care Among Refugees with Hepatitis B Virus Infection - Three U.S. Cities, 2006-2018.

An estimated 257 million persons worldwide have chronic hepatitis B virus (HBV) infection (1). CDC recommends HBV testing for persons from countries with intermediate to high HBV prevalence (≥2%), including newly arriving refugees (2). Complications of chronic HBV infection include liver cirrhosis and hepatocellular carcinoma, which develop in 15%-25% of untreated adults infected in infancy or childhood (3). HBV-infected patients require regular monitoring for both infection and sequelae. Several studies have evaluated initial linkage to HBV care for both refugee and nonrefugee immigrant populations (4-9), but none contained standardized definitions for either linkage to or long-term retention in care for chronic HBV-infected refugees. To assess chronic HBV care, three urban sites that perform refugee domestic medical examinations and provide primary care collaborated in a quality improvement evaluation. Sites performed chart reviews and prospective outreach to refugees with positive test results for presumed HBV infection during domestic medical examinations. Linkage to care (29%-53%), retention in care (11%-21%), and outreach efforts (22%-71% could not be located) demonstrated poor access to initial and ongoing HBV care. Retrospective outreach was low-yield. Interventions that focus on prospective outreach and addressing issues related to access to care might improve linkage to and retention in care.

Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009-2017: A cross-sectional analysis.

BACKGROUND: Between 2,000 and 19,000 Special Immigrant Visa (SIV) holders (SIVH) from Iraq and Afghanistan resettle in the United States annually. Despite the increase in SIV admissions to the US over recent years, little is known about the health conditions in SIV populations. We assessed the burden of select communicable and noncommunicable diseases (NCDs) in SIV adults to guide recommendations to clinicians in the US. METHODS AND FINDINGS: We analyzed overseas medical exam data in Centers for Disease Control and Prevention's (CDC) Electronic Disease Notification system (EDN) for 19,167 SIV Iraqi and Afghan adults who resettled to the US from April 2009 through December 2017 in this cross-sectional analysis. We describe demographic characteristics, tuberculosis screening results, self-reported NCDs, and risk factors for NCDs (such as obesity and tobacco use). In our data set, most SIVH were male (Iraqi: 59.7%; Afghan: 54.7%) and aged 18-44 (Iraqi: 86.3%; Afghan: 95.6%). About 2.3% of Afghan SIVH and 1.1% of Iraqi SIVH had a tuberculosis condition. About 0.3% of all SIVH reported having chronic hepatitis. Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use. Iraqi SIVH were 3.7 times more likely to have obesity (95% CI: 3.4-4.0), 2.5 times more likely to report diabetes (95% CI: 1.7-3.5), and 2.5 times more likely to be current or former smokers (95% CI: 2.3-2.7) than Afghan SIVH. Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and the underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. CONCLUSION: In this analysis, we found that 56.5% of all SIVH were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use. In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH. State public health agencies and clinicians doing domestic screening examinations of SIVH should consider screening for obesity-as per the CDC's Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees-and smoking and, if appropriate, referral to weight management and smoking cessation services. US clinicians can consider screening for other NCDs at the domestic screening examination. Future studies can explore the health profile of SIV populations, including the prevalence of mental health conditions, after integration into the US.

Health of Special Immigrant Visa holders from Iraq and Afghanistan after arrival into the United States using Domestic Medical Examination data, 2014-2016: A cross-sectional analysis.

BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (≥5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage.

Health screenings administered during the domestic medical examination of refugees and other eligible immigrants in nine US states, 2014-2016: A cross-sectional analysis.

BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program's potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination's impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research.

Cost-Effectiveness Analysis of Sequential Biologic Therapy with Ixekizumab Versus Secukinumab in the Treatment of Active Psoriatic Arthritis with Concomitant Moderate-to-Severe Psoriasis in the UK.

BACKGROUND: Interleukin-17A (IL-17A) antagonists are a recent innovation for treating psoriatic arthritis (PsA). There are currently no cost-effectiveness analyses (CEAs) comparing the IL-17A antagonists ixekizumab and secukinumab in PsA from a UK perspective. OBJECTIVE: We conducted a CEA from the UK National Health Service perspective to compare ixekizumab versus secukinumab in patients with PsA and concomitant moderate-to-severe plaque psoriasis. METHODS: A Markov model was developed based on the widely accepted York model. In biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, ixekizumab → ustekinumab → best supportive care (BSC) was compared with secukinumab → ustekinumab → BSC. For bDMARD-experienced patients, ixekizumab → BSC was compared with secukinumab → BSC. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders continued to receive the bDMARD in the continuous treatment period. PsARC nonresponders and patients who ceased continuous treatment transitioned to the trial period of the next treatment. RESULTS: Ixekizumab was less costly and provided more quality-adjusted life-years (QALYs) than secukinumab in bDMARD-naïve and -experienced patients based on list prices, although cost savings and QALY gains were small to modest. In bDMARD-naïve patients, total costs were £155,455 compared with £155,530 for secukinumab (year 2017 values). Total QALYs were 8.127 versus 7.989. In bDMARD-experienced patients, the corresponding values were £140,051 versus £140,264 for total costs and 3.996 versus 3.875 for total QALYs. CONCLUSION: Ixekizumab provided more QALYs at a marginally lower cost than secukinumab, and the results were most sensitive to changes in drug costs. Other factors, such as patient preferences for the number of injections and confidential price discounts, may be important considerations in clinical decision-making.

Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis.

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis (NMA) can inform evidence-based decision-making. OBJECTIVE: To evaluate the comparative efficacy and safety of approved bDMARDs in patients with PsA. METHODS: Bayesian NMA was conducted to compare the clinical efficacy of bDMARDs at weeks 12‒16 in bDMARD-naïve patients with PsA in terms of American College of Rheumatology (ACR) criteria, Psoriatic Arthritis Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI). Safety end points were evaluated in the overall mixed population of bDMARD-naive and bDMARD-experienced patients. RESULTS: For ACR, all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab 80 mg every 2 weeks (Q2W) was statistically superior to abatacept subcutaneous, apremilast and both regimens of ustekinumab; similar findings were observed for ixekizumab 80 mg Q4W. For PsARC response, ixekizumab did not significantly differ from other therapies, except for golimumab, infliximab and etanercept, which were superior to most other agents including ixekizumab. For PASI response, infliximab was numerically most effective, but was not statistically superior to ixekizumab, which was the next best performing agent. Analysis of safety end points identified few differences between treatments. CONCLUSION: Our NMA confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments.

Cost-effectiveness of TYRX absorbable antibacterial envelope for prevention of cardiovascular implantable electronic device infection.

AIMS: Infection is a major complication of cardiovascular implantable electronic device (CIED) therapy that usually requires device extraction and is associated with increased morbidity and mortality. The TYRX Antibacterial Envelope is a polypropylene mesh that stabilizes the CIED and elutes minocycline and rifampin to reduce the risk of post-operative infection. METHODS: A decision tree was developed to assess the cost-effectiveness of TYRX vs standard of care (SOC) following implantation of four CIED device types. The model was parameterized for a UK National Health Service perspective. Probabilities were derived from the literature. Resource use included drug acquisition and administration, hospitalization, adverse events, device extraction, and replacement. Incremental cost-effectiveness ratios (ICERs) were calculated from costs and quality-adjusted life-years (QALYs). RESULTS: Over a 12-month time horizon, TYRX was less costly and more effective than SOC when utilized in patients with an ICD or CRT-D. TYRX was associated with ICERs of £46,548 and £21,768 per QALY gained in patients with an IPG or CRT-P, respectively. TYRX was cost-effective at a £30,000 threshold at baseline probabilities of infection exceeding 1.65% (CRT-D), 1.95% (CRT-P), 1.87% (IPG), and 1.38% (ICD). LIMITATIONS AND CONCLUSIONS: Device-specific infection rates for high-risk patients were not available in the literature and not used in this analysis, potentially under-estimating the impact of TYRX in certain devices. Nevertheless, TYRX is associated with a reduction in post-operative infection risk relative to SOC, resulting in reduced healthcare resource utilization at an initial cost. The ICERs are below the accepted willingness-to-pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost-effective prevention option for CIED patients at high-risk of post-operative infection.

Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction.

BACKGROUND: People suffering from neurogenic bowel dysfunction (NBD) and an ineffective bowel regimen often suffer from fecal incontinence (FI) and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI) has been shown to reduce these symptoms and improve quality of life. AIM: To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC). METHODS: A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs), episodes of FI, urinary tract infections (UTIs), and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI), multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model. RESULTS: The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of £21,768 per patient was estimated for TAI versus continuing SBC alone. CONCLUSION: TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC.

Management of a soft tissue tumor in a child with Worster Drought syndrome using 810 nm diode laser - A case report.

BACKGROUND AND AIMS: An out-patient surgical procedure in the paediatric age group is a tough task for a surgeon, more so when compounded with mentally challenging conditions like cerebral palsy. Every step involved, either administration of local anaesthesia or handling sharp surgical instruments around the face or achieving haemostasis, can be a challenge, with compromise on patient safety. Neither undue restraint nor general anaesthesia is advisable, considering the magnitude of the procedure. In such cases, a safe, rapid and effective technique that can be comfortably performed under topical anaesthesia without use of sharp instruments or needles would be an ideal option. The purpose of this paper is to highlight one such situation, where an intra-oral soft tissue tumor was safely and effectively ablated using diode laser, under topical anaesthesia in a child with cerebral palsy concurrent with Worster Drought syndrome. RESULTS: Topical anaesthesia provided adequate conditions to ablate the tumor. A bloodless field was achieved, with no need for sutures. The procedure was completed in less than half the time required for a conventional approach. Postoperative follow-up of 3 months showed complete healing with no recurrence. CONCLUSIONS: Portable diode lasers are an effective tool for minor oral surgical procedures in paediatric population especially, children who are mentally challenged.

Cost-effectiveness of first-line induction and maintenance treatment sequences in non-squamous non-small cell lung cancer (NSCLC) in the U.S.

OBJECTIVES: Due to the lack of direct head-to-head trials, there are limited data regarding the comparative effectiveness of induction-maintenance sequences. The objective of this study was to develop a cost-effectiveness model to compare induction-maintenance sequences in the US for the treatment of advanced non-squamous NSCLC. MATERIALS AND METHODS: Decision analytic modelling was used to synthesize the treatment effect and baseline risk estimates for nine induction and maintenance treatment sequences, reflecting treatments used in the US. The model was structured using an area-under-the-curve approach and sensitivity analyses were conducted. Model validation was conducted by an independent third party. RESULTS: All active maintenance therapy-containing regimens, with the exception of gemcitabine+cisplatin (first-line)→erlotinib (maintenance), were more costly than induction-only regimens. Concerning treatments that may be cost effective, the incremental costs per life-year gained were $121,425, $148,994, and $191,270 for gemcitabine+cisplatin→erlotinib versus gemcitabine+cisplatin→best supportive care (BSC), pemetrexed+cisplatin→BSC versus gemcitabine+cisplatin→erlotinib, and for pemetrexed+cisplatin→pemetrexed versus pemetrexed+cisplatin→BSC, respectively. All other regimens were found to be dominated (carboplatin+paclitaxel→BSC; carboplatin+paclitaxel→erlotinib; carboplatin+paclitaxel→pemetrexed; bevacizumab+carboplatin+paclitaxel→bevacizumab) or extendedly dominated (cisplatin+gemcitabine→pemetrexed). Sensitivity analyses demonstrated stability. CONCLUSIONS: Depending on the specific cost-effectiveness threshold used by a decision maker, the most cost-effective treatment sequence may include the referent comparator gemcitabine+cisplatin and the studied regimens of gemcitabine+cisplatin→erlotinib, pemetrexed+cisplatin→BSC, or pemetrexed+cisplatin→pemetrexed.