Real-world utilization, patient characteristics, and treatment patterns among men with localized prostate cancer tested with the 17-gene genomic prostate score® (GPSTM) assay.

OBJECTIVES: Descriptive study focusing on real-world utilization and characteristics of men with prostate cancer tested with the 17-gene Genomic Prostate Score® (GPS™) assay by linking administrative claims and electronic health record (EHR) data with GPS results. METHODS: This retrospective, observational cohort study (January 1, 2013 to December 31, 2020) included men aged 40-80 years with localized prostate cancer claims, continuous enrollment in Optum's Integrated Claims data set, ≥1 day of EHR clinical activity, and a GPS result. Men were classified as undergoing definitive therapy (DT) (prostatectomy, radiation, or focal therapy) or active surveillance (AS). AS and DT distribution were analyzed across GPS results, National Comprehensive Cancer Network® (NCCN®) risk, and race. Costs were assessed 6 months after the first GPS result (index); clinical outcomes and AS persistence were assessed during the variable follow-up. All variables were analyzed descriptively. RESULTS: Of 834 men, 650 (77.9%) underwent AS and 184 (22.1%) DT. Most men had Quan-Charlson comorbidity scores of 1-2 and a tumor stage of T1c (index). The most common Gleason patterns were 3 + 3 (79.6%) (AS cohort) and 3 + 4 (55.9%) (DT cohort). The mean (standard deviation) GPS results at index were 23.2 (11.3) (AS) and 30.9 (12.9) (DT). AS decreased with increasing GPS result and NCCN risk. Differences between races were minimal. Total costs were substantially higher in the DT cohort. CONCLUSIONS: Most men with GPS-tested localized prostate cancer underwent AS, indicating the GPS result can inform clinical management. Decreasing AS with increasing GPS result and NCCN risk suggests the GPS complements NCCN risk stratification.

Patient and provider factors associated with colorectal cancer screening among average risk health plan enrollees in the US, 2015-2018.

BACKGROUND: To assess patient and primary care provider (PCP) factors associated with adherence to American Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF) guidelines for average risk colorectal cancer (CRC) screening. METHODS: Retrospective case-control study of medical and pharmacy claims from the Optum Research Database from 01/01/2014 - 12/31/2018. Enrollee sample was adults aged 50 - 75 years with ≥ 24 months continuous health plan enrollment. Provider sample was PCPs listed on the claims of average-risk patients in the enrollee sample. Enrollee-level screening opportunities were based on their exposure to the healthcare system during the baseline year. Screening adherence, calculated at the PCP level, was the percent of average-risk patients up to date with screening recommendations each year. Logistic regression modelling was used to examine the association between receipt of screening and enrollee and PCP characteristics. An ordinary least squares model was used to determine the association between screening adherence among the PCP's panel of patients and patient characteristics. RESULTS: Among patients with a PCP, adherence to ACS and USPSTF screening guidelines ranged from 69 to 80% depending on PCP specialty and type. The greatest enrollee-level predictors for CRC screening were having a primary/preventive care visit (OR = 4.47, p < 0.001) and a main PCP (OR = 2.69, p < 0.001). CONCLUSIONS: Increased access to preventive/primary care visits could improve CRC screening rates; however, interventions not dependent on healthcare system contact, such as home-based screening, may circumvent the dependence on primary care visits to complete CRC screening.

Adherence to fecal immunochemical test screening among adults at average risk for colorectal cancer.

PURPOSE: This study examined adherence to screening for fecal immunochemical test (FIT). METHODS: Adults (≥ 50-75) with a FIT between 1/1/2014 and 6/30/2019 in MarketScan administrative claims were selected (index = earliest FIT). Patients were followed for 10 years pre- and 3 years post-index. Patients at increased risk for CRC or with prior screening were excluded. Year over year adherence was measured post-index. RESULTS: Of 10,253 patients, the proportion adherent to repeat testing at year 2 was 23.4% and 10.6% at year 3. Of 76.6% not adherent in year 2, 5.4% were adherent in year 3. CONCLUSION: Results suggest adherence to FIT tests is poor, minimizing potential benefits. Future studies are needed to consider alternative test options and whether more choice will improve long-term adherence.

Incident colorectal cancer screening and associated healthcare resource utilization and Medicare cost among Medicare beneficiaries aged 66-75 years in 2016-2018.

BACKGROUND: While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. METHODS: Using 20% Medicare random sample data, the study population included 2016-2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66-75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an "incident screening". Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. RESULTS: Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). CONCLUSIONS: The 2016-2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.

Cross-sectional adherence with the multi-target stool DNA test for colorectal cancer screening in a large, nationally insured cohort.

PURPOSE: Colorectal cancer (CRC) is the second most deadly cancer in the USA. Early detection can improve CRC outcomes, but recent national screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test. We evaluated cross-sectional mt-sDNA test completion in a population of commercially and Medicare-insured patients. METHODS: Participants included individuals ages 50 years and older with commercial insurance or Medicare, with a valid mt-sDNA test shipped by Exact Sciences Laboratories LLC between January 1, 2018, and December 31, 2018 (n = 1,420,460). In 2020, we analyzed cross-sectional adherence, as the percent of successfully completed tests within 365 days of shipment date. RESULTS: Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance. Adherence increased with age: 60.8% for ages 50-64, 71.3% for ages 65-75, and 74.7% for ages 76 + years. Participants with mt-sDNA tests ordered by gastroenterologists had a higher adherence rate (78.3%) than those with orders by primary care clinicians (67.2%). Geographically, adherence rates were highest among highly rural patients (70.8%) and ordering providers in the Pacific region (71.4%). CONCLUSIONS: Data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test, supporting its role as an accepted, noninvasive option for average-risk CRC screening. Attributes of mt-sDNA screening, including home-based convenience and accompanying navigation support, likely contributed to high completion rates.

Piezo1 integration of vascular architecture with physiological force.

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

Cligosiban, A Novel Brain-Penetrant, Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents.

INTRODUCTION: Few treatments are available for men with premature ejaculation (PE); oxytocin (OT) receptor antagonism in the central nervous system (CNS) is a potential new approach. AIM: To determine if cligosiban selectively inhibits human OT receptors, penetrates the CNS, shows pharmacology in the CNS, and effects ejaculatory physiology in pre-clinical systems. METHODS: Experiments complied with United Kingdom legislation and were subject to local ethical review. In vitro potency and selectivity of cligosiban was assessed using recombinant and native OT receptor systems including both neuronal and non-neuronal cell types. Selectivity was determined over neighboring V1A, V1B, and V2 vasopressin receptors using a combination of recombinant and native vasopressin receptor assay systems. To determine an effect on central OT receptors and on ejaculation, cligosiban was evaluated in 2 anesthetized rat models-the electromyography model of ejaculatory physiology and a model of OT-mediated CNS neuronal firing. The CNS penetration of cligosiban was also determined by measuring cerebrospinal fluid and plasma drug concentrations following an intravenous (IV) infusion in rats. MAIN OUTCOME MEASURE: These were functional measures of pharmacology in vitro, in cell lines and tissues, and in vivo in rats. RESULTS: Cligosiban is a potent OT receptor antagonist, with a base dissociation constant of 5.7 nmol/L against native human uterine smooth muscle cell OT receptors. Cligosiban displays similar antagonistic potency against human recombinant and rat native OT receptors, including neuronal OT receptors. Cligosiban demonstrates >100-fold selectivity over human V1A, V1B, and V2 vasopressin receptors. In the electromyography model, cligosiban (0.9 mg/kg, IV bolus) reduced the bulbospongiosum burst pattern and contraction amplitude associated with ejaculation. In the anesthetized CNS neuronal firing model, the same dosing regimen of cligosiban (0.9 mg/kg IV bolus) modulated the OT-mediated response in the nucleus tractus solitarius. After systemic dosing to rats, cligosiban showed good CNS penetration. CLINICAL IMPLICATIONS: As the first highly selective and centrally penetrant OT receptor antagonist, cligosiban represents a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. STRENGTH & LIMITATIONS: The pharmacology and selectivity of cligosiban is determined using functional assays in recombinant cell lines, native cell lines, and tissue. Functional outcomes in in vivo systems are linked to CNS measures of pharmacology. The translation of the animal models of ejaculation to PE in man is unproven. CONCLUSION: Cligosiban, a potent, selective OT receptor antagonist, demonstrated CNS penetration and pharmacology and, using the same dosing regimen, inhibited apomorphine-induced ejaculation in rats. Cligosiban is a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. Wayman C, Russell R, Tang K, et al. Cligosiban, A Novel Brain Penetrant Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents. J Sex Med 2018;15:1698-1706.

Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells.

CRACR2A protein is described in T cells as an EF-hand-containing modulator of calcium-release-activated calcium (CRAC) channels. Here we sought relevance to calcium entry of endothelial cells. Unexpectedly, short interfering RNA designed to deplete CRACR2A had no effect on CRAC channels in endothelial cells but reduced the abundance of a protein with about twice the mass of CRACR2A. Reference to gene sequence data indicated the potential for a variant transcript encoding a C-terminal Rab GTPase extension of CRACR2A. Full-length cloning demonstrated expression of the long variant in endothelial cells. It was designated CRACR2A-L. Sequence analysis suggested it to be a previously unrecognised member of the Rab GTPase family. It made a positive contribution to endothelial tube formation. The data suggest that endothelial cells contain a long variant of CRACR2A which is an EF-hand-containing Rab protein that lacks impact on CRAC channels.

Polio survivors' perceptions of the meaning of quality of life and strategies used to promote participation in everyday activities.

INTRODUCTION: The term 'post-polio syndrome' (PPS) is used to describe new and late manifestations of poliomyelitis that occur later in life. Research in this area has focused upon health status rather than its effect on quality of life. AIM: To gain an in-depth understanding of the meaning of quality of life for polio survivors and to determine the type of strategies that are used by people with PPS and the support that they consider as important to facilitate participation in everyday life activities that have an impact on their quality of life. METHOD: Six focus groups were conducted with 51 participants from two regions in England. Data were audio-taped and analysed using thematic analysis. RESULTS: Our research found that polio survivors used terms used to describe quality of life which could be associated with that of happiness. Our research has identified resolvable factors that influence quality of life namely inaccessible environments, attitudes of health-care professionals and societal attitudes. Polio survivors have tried alternative therapies, chiefly acupuncture and massage, and found them to be effective in enhancing their quality of life. CONCLUSION: It is suggested that health-care professionals should consider factors which influence happiness and implement a person-centred approach with the views of the polio survivor being listened to. The three factors that influenced quality of life could be resolved by health-care professionals and by society. With regard to strategies used, we suggest that polio survivors should have access to the treatments that they perceive as important, although further research is required to design optimal interventions for this client group.

Using the Technology Acceptance Model to explore community dwelling older adults' perceptions of a 3D interior design application to facilitate pre-discharge home adaptations.

BACKGROUND: In the UK occupational therapy pre-discharge home visits are routinely carried out as a means of facilitating safe transfer from the hospital to home. Whilst they are an integral part of practice, there is little evidence to demonstrate they have a positive outcome on the discharge process. Current issues for patients are around the speed of home visits and the lack of shared decision making in the process, resulting in less than 50 % of the specialist equipment installed actually being used by patients on follow-up. To improve practice there is an urgent need to examine other ways of conducting home visits to facilitate safe discharge. We believe that Computerised 3D Interior Design Applications (CIDAs) could be a means to support more efficient, effective and collaborative practice. A previous study explored practitioners perceptions of using CIDAs; however it is important to ascertain older adult's views about the usability of technology and to compare findings. This study explores the perceptions of community dwelling older adults with regards to adopting and using CIDAs as an assistive tool for the home adaptations process. METHODS: Ten community dwelling older adults participated in individual interactive task-focused usability sessions with a customised CIDA, utilising the think-aloud protocol and individual semi-structured interviews. Template analysis was used to carry out both deductive and inductive analysis of the think-aloud and interview data. Initially, a deductive stance was adopted, using the three pre-determined high-level themes of the technology acceptance model (TAM): Perceived Usefulness (PU), Perceived Ease of Use (PEOU), Actual Use (AU). Inductive template analysis was then carried out on the data within these themes, from which a number of sub-thmes emerged. RESULTS: Regarding PU, participants believed CIDAs served as a useful visual tool and saw clear potential to facilitate shared understanding and partnership in care delivery. For PEOU, participants were able to create 3D home environments however a number of usability issues must still be addressed. The AU theme revealed the most likely usage scenario would be collaborative involving both patient and practitioner, as many participants did not feel confident or see sufficient value in using the application autonomously. CONCLUSIONS: This research found that older adults perceived that CIDAs were likely to serve as a valuable tool which facilitates and enhances levels of patient/practitioner collaboration and empowerment. Older adults also suggested a redesign of the interface so that less sophisticated dexterity and motor functions are required. However, older adults were not confident, or did not see sufficient value in using the application autonomously. Future research is needed to further customise the CIDA software, in line with the outcomes of this study, and to explore the potential of collaborative application patient/practitioner-based deployment.

Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin.

RATIONALE: Calcium entry is pivotal in the heart and blood vessels, but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitization, and antiatherosclerotic effects. OBJECTIVE: To investigate the relevance of calcium channels to adipocytes and the production of adiponectin. METHODS AND RESULTS: Microarray analysis led to identification of transient receptor potential canonical (TRPC)1 and TRPC5 as channel subunits that are induced when adipocytes mature. Both subunits were found in perivascular fat of patients with atherosclerosis. Intracellular calcium and patch-clamp measurements showed that adipocytes exhibit constitutively active calcium-permeable nonselective cationic channels that depend on TRPC1 and TRPC5. The activity could be enhanced by lanthanum or rosiglitazone, known stimulators of TRPC5 and TRPC5-containing channels. Screening identified lipid modulators of the channels that are relevant to adipose biology. Dietary ω-3 fatty acids (eg, α-linolenic acid) were inhibitory at concentrations that are achieved by ingestion. The adipocyte TRPC1/TRPC5-containing channel was functionally negative for the generation of adiponectin because channel blockade by antibodies, knock-down of TRPC1-TRPC5 in vitro, or conditional disruption of calcium permeability in TRPC5-incorporating channels in vivo increased the generation of adiponectin. The previously recognized capability of α-linolenic acid to stimulate the generation of adiponectin was lost when calcium permeability in the channels was disrupted. CONCLUSIONS: The data suggest that TRPC1 and TRPC5 contribute a constitutively active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which ω-3 fatty acids enhance the anti-inflammatory adipokine, adiponectin.

Trends in Colorectal Cancer Screening from the National Health Interview Survey: Analysis of the Impact of Different Modalities on Overall Screening Rates.

Colorectal cancer is the second leading cause of cancer-related mortality in adults in the United States. Despite compelling evidence of improved outcomes in colorectal cancer, screening rates are not optimal. This study aimed to characterize colorectal cancer screening trends over the last two decades and assess the impact of various screening modalities on overall colorectal cancer screening rates. Using National Health Interview Survey data from 2005 to 2021, we examined colorectal cancer screening [colonoscopy, multitarget stool DNA (mt-sDNA), fecal occult blood test (FOBT)/fecal immunochemical test, sigmoidoscopy, CT colonography] rates among adults ages 50-75 years (n = 85,571). A pseudo-time-series cross-sectional (pseudo-TSCS) analysis was conducted including a random effects generalized least squares regression model to estimate the relative impact of each modality on changes in colorectal cancer screening rates. Among 50 to 75 year olds, the estimated colorectal cancer screening rate increased from 47.7% in 2005 to 69.9% in 2021, with the largest increase between 2005 and 2010 (47.7%-60.7%). Rates subsequently plateaued until 2015 but increased from 63.5% in 2015 to 69.9% in 2018. This was primarily driven by the increased use of mt-sDNA (2.5% in 2018 to 6.6% in 2021). Pseudo-TSCS analysis results showed that mt-sDNA contributed substantially to the increase in overall screening rates (77.3%; P < 0.0001) between 2018 and 2021. While colorectal cancer screening rates increased from 2005 to 2021, they remain below the 80% goal. The introduction of mt-sDNA, a noninvasive screening test may have improved overall rates. Sustained efforts are required to further increase screening rates to improve patient outcomes and offering a range of screening options is likely to contribute to achieving this goal. PREVENTION RELEVANCE: This retrospective study highlights the importance of convenient stool-based colorectal cancer screening options to achieve the national goal of 80% for overall colorectal cancer screening rates. Empowering screening-eligible individuals with a choice for their colorectal cancer screening tests is imperative.

Colorectal cancer screening uptake and adherence by modality at a large tertiary care center in the United States: a retrospective analysis.

OBJECTIVE: Real-world data is crucial to inform existing opportunistic colorectal cancer (CRC) prevention programs. This study aimed to assess CRC screening adherence and utilization of various screening modalities within a Primary Care network over a three-year period (2017-2019). METHODS: A retrospective review of individuals aged 50-75 years at average CRC risk, with at least one clinic visit in the previous 24 months. The primary outcome, CRC screening adherence (overall and by modality) was examined among the entire eligible population and newly adherent individuals each calendar year. The final sample included 107,366 patients and 218,878 records. RESULTS: Overall CRC screening adherence increased from 71% in 2017 to 78% in 2019. For "up-to-date" individuals, colonoscopy was the predominant modality (accounting for approximately 74%, versus 4% of adherence for non-invasive options). However, modality utilization trends changed over time in these individuals: mt-sDNA increased 10.2-fold, followed by FIT (1.6-fold) and colonoscopy (1.1-fold). Among newly adherent individuals, the proportion screened by colonoscopy and FOBT decreased over time (89% to 80% and 2.4% to 1.2%, respectively), while uptake of FIT and mt-sDNA increased (7.7% to 11.5% and 0.9% to 6.8%, respectively). Notably, FIT and mt-sDNA increases were most evident in age and race-ethnicity groups with the lowest screening rates. CONCLUSIONS: In an opportunistic CRC screening program, adherence increased but remained below the national 80% goal. While colonoscopy remained the most utilized modality, new colonoscopy uptake declined, compared with rising mt-sDNA and FIT utilization. Among minority populations, new uptake increased most with mt-sDNA and FIT.

Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation.

RATIONALE: Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown. OBJECTIVE: The aim of this study was to investigate the relevance of Orai1 and CRAC channels to vascular endothelial growth factor (VEGF) and endothelial tube formation. METHODS AND RESULTS: In human umbilical vein endothelial cells, Orai1 disruption by short-interfering RNA or dominant-negative mutant Orai1 inhibited calcium release-activated (store-operated) calcium entry, VEGF-evoked calcium entry, cell migration, and in vitro tube formation. Expression of exogenous wild-type Orai1 rescued the tube formation. VEGF receptor-2 and Orai1 partially colocalized. Orai1 disruption also inhibited calcium entry and tube formation in endothelial progenitor cells from human blood. A known blocker of the immune cell CRAC channel (3-fluoropyridine-4-carboxylic acid (2',5'-dimethoxybiphenyl-4-yl)amide) was a strong blocker of store-operated calcium entry in endothelial cells and inhibited calcium entry evoked by VEGF in 3 types of human endothelial cell. The compound lacked effect on VEGF-evoked calcium-release, STIM1 clustering, and 2 types of transient receptor potential channels, TRPC6 and TRPV4. Without effect on cell viability, the compound inhibited human endothelial cell migration and tube formation in vitro and suppressed angiogenesis in vivo in the chick chorioallantoic membrane. The compound showed 100-fold greater potency for endothelial compared with immune cell calcium entry. CONCLUSIONS: The data suggest positive roles for Orai1 and CRAC channels in VEGF-evoked calcium entry and new opportunity for chemical modulation of angiogenesis.

Living with polio and postpolio syndrome in the United Kingdom.

The term Postpolio Syndrome (PPS) is used to describe new and late manifestations of poliomyelitis that occur later in life in polio survivors. Polio had been eradicated in the United Kingdom (UK) and most of Europe, although this is not the case in all countries. Research in this area has tended to focus upon the impact of polio and PPS on health status and functional health rather than its overall effect on people's lives. This study's two main aims were to explore the ways in which polio and PPS in the UK has affected the respondents' lives and to ascertain their views about how the quality of life could be improved. The two questions were as follows: (1) How has the health of people with polio and PPS affected their quality of life? (2) What would people with polio and PPS change to improve their quality of life? Deductive content analysis using existing qualitative data from a cross-sectional survey of 336 returned questionnaires from persons with polio and PPS was carried out. The average age of the participants was 54 years. Our research found that polio survivors valued social occupations and participation in family life. Our research has also shown that healthcare professionals still do not understand polio and PPS and this lack of understanding influences their clients' quality of life. Finances and accessibility of environments also influence participation in chosen occupations. Rehabilitation programmes for people with polio and PPS need to be targeted towards maintaining and improving accessible environments and participation in chosen occupations, and healthcare professionals need to ensure that persons with polio and PPS are referred to persons with specific expertise in this area.

Opportunities and Challenges in Screening for Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of mortality in the United States. Outcomes are greatly improved if CRC is detected early; hence, screening is currently recommended for adults aged 45 years and older at average risk for the disease. Despite this recommendation and the availability of accurate screening tests, the CRC screening rates are below those recommended. The goal of this study was to identify temporal trends (from 2015 to 2019) in CRC screening rates and the utilization of screening tests recommended for CRC detection among average-risk individuals within the St Elizabeth Healthcare system in Kentucky, United States. The primary population of interest was patients aged 50-75 years (the CRC screening was recommended for this age group at the time of the study). Deidentified data were sourced from patients' electronic health records, and the results showed that screening rates increased significantly from 26% in 2015 to 49% in 2019 (<0.0001). The incidence of any screening test also increased significantly from 2015 to 2019, for those who were due for screening (P < 0.05) and for the entire cohort (P < 0.1). The use of multitarget stool DNA (mt-sDNA) increased 40-fold over the study timeframe (P < 0.05). These study results confirm that CRC screening rates remain suboptimal, although incidence and adherence improved significantly in those aged 50-75 years from 2015 to 2019. The growing adoption and availability of mt-sDNA may be correlated with an increase in overall screening in this average-risk population.

Prospective Assessment of the Diagnostic Accuracy of Multi-site Photoplethysmography Pulse Measurements for Diagnosis of Peripheral Artery Disease in Primary Care.

Peripheral arterial disease (PAD) is associated with cerebral and coronary artery disease. Symptomatic PAD affects about 5% of people over 55 years; many more have asymptomatic PAD. Early detection enables modification of arterial disease risk factors. Diagnostically, assessment of symptoms or signs can be unreliable; ankle brachial pressure index (ABPI) testing is time-consuming and few healthcare professionals are properly trained. This study assessed the diagnostic accuracy of multi-site photoplethysmography (MPPG), an alternative non-invasive test for PAD, in primary care. PAD patients identified from general practice registers were age- and sex-matched with controls. Participants were assessed using MPPG, ABPI and duplex ultrasound (DUS). Outcome measures were sensitivity and specificity of MPPG and ABPI (relative to DUS) and concordance. MPPG test results were available in 249 of 298 eligible participants from 16 practices between May 2015 and November 2016. DUS detected PAD in 101/249 (40.6%). MPPG sensitivity was 79.8% (95% confidence interval [CI] 69.9-87.6%), with specificity 71.9% (95% CI 63.7-79.2%). ABPI sensitivity was 80.2% (95% CI 70.8-87.6%), with specificity 88.6% (95% CI 82-93.5%). With comparable sensitivity to ABPI, MPPG is quick, automated and simpler to do than ABPI; it offers the potential for rapid and accessible PAD assessments in primary care.

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

OBJECTIVES: To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. METHODS: This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. RESULTS: In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. CONCLUSIONS: Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Colorectal cancer (CRC) is a prominent healthcare concern the United States, which accounted for 149,500 new cases and 52,980 deaths in 2021. Screening is effective for diagnosing the condition at earlier more treatable stages, and reducing deaths. However, screening is largely underutilized in part due to perceived cost barriers. This observational study used insurance claims data to calculate healthcare costs, resource use, and lost productivity for CRC screening in an average-risk population aged 50­75 years. A total of 903,831 individuals were identified by test groups: multi-target stool DNA test (mt-sDNA test; 29,614 individuals), fecal immunochemical test (FIT; 254,002 individuals), guaiac-based fecal occult blood test (FOBT; 112,757 individuals) and colonoscopy (507,458 individuals). Adjusted costs for initial screening were $3,029 for colonoscopy, $752 for mt-sDNA, $45 for FIT, and $153 for FOBT. Adjusted colonoscopy-related costs combined across the six months following the initial screening were $146 for the colonoscopy cohort, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Overall, screening colonoscopy was accompanied by the highest productivity loss and up-front costs, suggesting potential cost benefits for noninvasive screening modalities ­ mt-sDNA, FIT, and FOBT; however, the more frequent screening interval required by FIT and FOBT resulted in a higher estimated average yearly screening cost.

Colorectal screening among average risk individuals in the United States, 2015-2018.

Colorectal cancer screening rates are important metrics for public health and quality indicators for health care systems; however, published estimates of colorectal cancer screening rates often include both high-risk and average-risk patients, and the use of different epidemiologic methods makes between-study comparisons tenuous. The objective of this study was to measure the proportion of average-risk American adults who are up to date with colorectal cancer screening guidelines and examine the impact of evaluation methods on screening rate estimates. This repeated cross-sectional study used administrative claims to identify individuals aged 50-75 years between 2015 and 2018 with ≥ 1-year of continuous health plan enrollment. Sensitivity analyses to replicate prior studies in the literature included: 1) retrospective cohort study requiring ≥ 10 years of continuous enrollment to identify the most current screening rates (2018), and 2) inclusion of individuals with higher colorectal cancer risk. A total of 2,579,898; 2,948,064; 3,312,882; and 2,752,864 individuals were included in the 2015, 2016, 2017, and 2018 populations, respectively. In the cross-sectional sample, the proportion of individuals with up-to-date colorectal cancer screening was 51.8%, 51.3%, 51.0%, and 51.1% in 2015, 2016, 2017, and 2018, respectively. The inclusion of high-risk individuals increased estimates approximately 37%. Using a retrospective cohort design, 67.5% of average-risk individuals were up to date in 2018. This study demonstrated the impact of methodological differences on rate estimates. Efforts to track screening rates require transparency in measurement methods to accurately evaluate progress in improving rates.

Rates of Follow-up Colonoscopy After a Positive Stool-Based Screening Test Result for Colorectal Cancer Among Health Care Organizations in the US, 2017-2020.

Importance: Noninvasive stool-based screening tests (SBTs) are effective alternatives to colonoscopy. However, a positive SBT result requires timely follow-up colonoscopy (FU-CY) to complete the colorectal cancer screening paradigm. Objectives: To evaluate FU-CY rates after a positive SBT result and to assess the association of the early COVID-19 pandemic with FU-CY rates. Design, Setting, and Participants: This mixed-methods cohort study included retrospective analysis of deidentified administrative claims and electronic health records data between June 1, 2015, and June 30, 2021, from the Optum Labs Data Warehouse and qualitative, semistructured interviews with clinicians from 5 health care organizations (HCOs). The study population included data from average-risk primary care patients aged 50 to 75 years with a positive SBT result between January 1, 2017, and June 30, 2020, at 39 HCOs. Main Outcomes and Measures: The primary outcome was the FU-CY rate within 1 year of a positive SBT result according to patient age, sex, race, ethnicity, insurance type, Charlson Comorbidity Index (CCI), and prior SBT use. Results: This cohort study included 32 769 individuals (16 929 [51.7%] female; mean [SD] age, 63.1 [7.1] years; 2092 [6.4%] of Black and 28 832 [88.0%] of White race; and 825 [2.5%] of Hispanic ethnicity). The FU-CY rates were 43.3% within 90 days of the positive SBT result, 51.4% within 180 days, and 56.1% within 360 days (n = 32 769). In interviews, clinicians were uniformly surprised by the low FU-CY rates. Rates varied by race, ethnicity, insurance type, presence of comorbidities, and SBT used. In the Cox proportional hazards regression model, the strongest positive association was with multitarget stool DNA use (hazard ratio, 1.63 [95% CI, 1.57-1.68] relative to fecal immunochemical tests; P < .001), and the strongest negative association was with the presence of comorbidities (hazard ratio, 0.64 [95% CI, 0.59-0.71] for a CCI of >4 relative to 0; P < .001). The early COVID-19 pandemic was associated with lower FU-CY rates. Conclusions and Relevance: This study found that FU-CY rates after a positive SBT result for colorectal cancer screening were low among an average-risk population, with the median HCO achieving a 53.4% FU-CY rate within 1 year. Socioeconomic factors and the COVID-19 pandemic were associated with lower FU-CY rates, presenting opportunities for targeted intervention by clinicians and health care systems.