The availability of Medicare Part D pharmacy coverage may increase veterans’ options for obtaining medications outside of the Department of Veterans Affairs (VA) pharmacies. However, availability of Part D coverage raises the potential that veterans may be receiving similar medications from VA and non-VA pharmacies. The VA’s personal health record portal, My HealtheVet, allows veterans to self-enter the non-VA medications that they obtained from community-based pharmacies, including those reimbursed by Medicare Part D. The Blue Button medication view feature of My HealtheVet allows veterans to view and download their VA and self-entered non-VA medication history.To examine whether the use by veterans of the Blue Button feature of My HealtheVet was associated with less acquisition of similar medications from VA and community-based pharmacies reimbursed by Medicare Part D.This study included a national sample of veterans who were new My HealtheVet users during fiscal year 2013  and who used the Blue Button medication view feature of My HealtheVet at least once (users). We compared these veterans with a random sample of veterans who were not registered to use My HealtheVet (nonusers). From these groups, we identified veterans who were enrolled in Part D. We used multiple logistic regression analysis to assess the association of Blue Button medication view use with obtaining medications from the same drug classes (with overlap of 7 or more days) from VA and Part D-reimbursed pharmacies.P < 0.001). A larger percentage of users than nonusers obtained medications from VA and Part D-reimbursed pharmacies with overlapping days supply from the same drug classes . However, for veterans who obtained greater numbers of 30-day supplies (82 or more), a significantly smaller percentage of users than nonusers obtained overlapping medications from VA and Part D-reimbursed pharmacies. Moreover, controlling for the total number of 30-day supplies that veterans received, the odds of obtaining medications from VA and Part D-reimbursed pharmacies with days supply that overlapped by at least 7 days for the same drug classes was 18% lower for users than nonusers (P=0.002).There were 7,973 My HealtheVet medication view users and 65,985 nonusers. During a 12-month period, medication view users received more 30-day supplies of medications  than nonusers, on average (152.1 vs 71.3, Veterans who used the Blue Button medication view feature of My HealtheVet obtained a larger number of 30-day supplies of medications from VA pharmacies than nonusers. For veterans who obtained a larger number of 30-day supplies of medications, use of the Blue Button medication view feature of My HealtheVet was associated with less overlap in days supply of medication from the same drug class from VA and Part D-reimbursed pharmacies. What is already known about this subjectHealth care providers and patients have previously reported that use of personal health portal features such as the Blue Button feature of the Department of Veterans Affairs (VA) My HealtheVet patient portal can improve aspects of care coordination; however, effects on medication use are unknown.What this study addsThis study found that veterans using the Blue Button medication view feature of the My HealtheVet patient portal received more medications from VA pharmacies.Among veterans receiving larger numbers of medications, use of the Blue Button medication view feature of the My HealtheVet patient portal was associated with less acquisition of similar medications from VA and community-based pharmacies reimbursed by the Medicare Part D prescription drug benefit.1 Moreover, 46.8% of the US veteran population (over 9.1 million veterans) are enrolled in or use Department of Veterans Affairs (VA) health care.2 Veterans who receive care at VA health care facilities may obtain prescription medications from VA pharmacies. Many of these veterans have complex health care needs because they have multiple chronic conditions, need highly specialized care, and receive health care from VA and non-VA providers.6 Consequently, many of these veterans may be receiving medications from VA and non-VA prescribers. The US Medicare system is a national health insurance program for individuals who meet the age requirement, have a disability, or have end-stage kidney disease. For veterans who meet 1 or more of these requirements, non-VA care may be covered by the Medicare insurance program. In the Medicare system, Medicare Part D is an optional federal government program, which went into effect in January 2006 to create an outpatient prescription drug benefit to help Medicare beneficiaries, including veterans who are also receiving care at VA health care facilities, pay for self-administered prescription drugs. The availability of the Medicare Part D prescription drug benefit may facilitate access to non-VA medications. In 2018, the Survey of Veteran Enrollees’ Health and Use of Health Care estimated that approximately 17% of veterans enrolled in VA health care were also enrolled in Medicare Part D.7Approximately 13% of all adults in the United States are veterans, including over 50% of men who meet Medicare’s age requirement (≥ 65 years).8The availability of Medicare Part D prescription drug coverage may increase options for veterans to obtain medications. For example, VA users who are enrolled in Medicare may be receiving medications from non-VA prescribers that are reimbursed under Medicare Part D because of recent stays at non-VA hospitals, preferences for specialty care outside the VA, or closer proximity of non-VA providers to their homes. This additional source of coverage raises the potential that veterans may be receiving similar medications from VA and non-VA pharmacies. If veterans are treated by multiple VA and non-VA prescribers with limited information sharing, the VA’s ability to limit possible duplication of therapy and prevent untoward consequences of polypharmacy might be inhibited.11 including information sharing with their health care providers about their medications.12 Veterans can access the My HealtheVet portal and use its various features through multiple platforms, including web browsers accessed on a computer, tablet, or smartphone. The Blue Button feature in the portal enables veterans to access and download a copy of their VA health records into a text, PDF, or XML file that can be read, printed, or saved and then shared with health care providers.14 The Blue Button medication view feature provides access to information about the prescriptions processed by VA pharmacies in the previous 15 months and all medications self-entered into My HealtheVet by the veteran.15Online personal health record portals such as the VA’s My HealtheVet portal have tremendous potential to support access and organization of information about an individual’s health,17 However, other pilot randomized controlled trials of Blue Button that have compared the medical records of providers who care for veterans receiving VA and community-based care did not reveal improvements in medication reconciliation.18 Whether use of personal health record features such as Blue Button is associated with decreased acquisition of similar medications from multiple health care systems remains unknown.Health care providers and patients have previously reported that use of personal health portal features such as Blue Button can improve aspects of care coordination.In this study, we examined whether veterans’ use of the Blue Button medication view feature of the My HealtheVet patient portal was associated with less acquisition of similar medications from VA and community-based pharmacies reimbursed by the Medicare Part D prescription drug benefit.eVet use among veterans receiving VA health care, including effects on VA health care use and dual use of services from VA and community providers reimbursed by Medicare. The focus of this analysis was the association of My HealtheVet use with acquisition of similar medications from VA and community pharmacies. The study included a national sample of veterans who were newly authenticated users of My HealtheVet during fiscal year 2013  and who used the Blue Button medication view feature at least once (users). We compared these Blue Button users with a random sample of veterans who were not registered to use My HealtheVet .Data were collected as part of a retrospective analysis that examined My HealtheVet Blue Button medication view feature, the index date was defined as the date of the first use of this feature. For nonusers of My HealtheVet, the index date was July 1, 2013. The mean number of months on Medicare Part D was 9.5 for veterans in the medication view user group and 10.8 in the My HealtheVet nonuser group during the 12-month period following the index date. This study was approved by the Institutional Review Board at the Edward Hines, Jr. VA Hospital.From these 2 groups, we identified veterans who were also enrolled in Medicare Part D for at least 1 month following the index date. Veterans who were deceased, aged younger than 18 years or older than 104 years, or missing data on variables included as covariates in adjusted models  were excluded from the sample. For veterans who used the My Health19 The Centers for Medicare & Medicaid Services (CMS) requires that insurance companies submit data to CMS on all prescriptions that have been dispensed and paid through the Part D program. These prescriptions are recorded in the Prescription Drug Event file. The Part D Slim file contains a subset of variables from this file that are of particular interest to researchers .Medication acquisition was assessed during the 12-month period following the index date. We obtained data from the VA Managerial Cost Accounting (MCA) National Data Extract (NDE) Pharmacy datasets and the Medicare Part D “Slim” file. Medication acquisition was measured as the number of 30-day medication supplies  and the number of different drug classes that veterans received from VA and Part D-reimbursed pharmacies. The drug classes were based on the VA Drug Classification system, which separates drugs, supplies, and diagnostics into different categories based on their characteristics. Drug classes in this system may vary in their level of specificity; however, this classification system provides general categories of drugs and mostly follows the American Hospital Formulary Service drug classifications.For medications from VA pharmacies, the VA drug classes were obtained from the VA MCA NDEs. To assign VA drug classes to medications in the Part D Slim file, we linked records in this file with the VA’s National Drug File using National Drug Code numbers. The VA National Drug File contains product-level information about medications dispensed by VA pharmacies such as the product’s National Drug Code number and VA drug class. To assess whether veterans obtained similar medications from VA and community-based pharmacies, we determined the percentage of veterans who received medications from the same drug class with overlapping days supply from VA and community-based pharmacies reimbursed by the Medicare Part D drug benefit.Data for medications from the community-based pharmacies that we used to assess overlapping days supply was obtained from the Medicare Part D Slim file. Overlap of medication supplies from VA or community-based pharmacies of 7 days or more was operationalized dichotomously .20 The distance between the nearest VA facility to the veteran and the center of the ZIP code associated with the veteran’s address was used to estimate distance to the nearest VA. A veteran’s VA enrollment group, a classification system used to determine copayments for VA services based on disability rating, income, and other factors , was determined using the VA Enrollment file. The socioeconomic status of the veteran’s geographic area was estimated using data on the median household income in the veteran’s county of residence from the Area Health Resources Files. ZIP code information was used to determine the urbanicity of the veteran’s residence.21 Overall health status was estimated through the CMS Hierarchical Condition Category (HCC) risk-adjustment model for community-dwelling populations.23Characteristics were assessed during the 12-month period after the index date. Information about veterans’ characteristics were obtained from the VA Medical SAS Databases and included sex, age, race, ethnicity, and US geographic region of residence .eVet usage data.Registration for My HealtheVet and use of the Blue Button medication view feature were obtained from VA My Health24 We calculated the propensity score for each veteran as the predicted probability of using the Blue Button medication view feature from multiple logistic regression analyses of patient characteristics shown in 24 We calculated the SDs in characteristics between the groups to ensure that characteristics were similar between comparison groups after weighting.Analyses were conducted using Stata version 14 (StataCorp). To balance characteristics between users and nonusers, we used propensity score weighting.25To examine the types and sources of medications, we assessed the number of 30-day supplies and the number of different medication classes that veterans received from VA, Part D-reimbursed, or both types of pharmacies. We compared these between users and nonusers. We also examined how medication acquisition was distributed between VA and Part D-reimbursed pharmacies. Additionally, for all pharmacy use groups, we examined the most frequently occurring drug classes for which the days supply of medications from VA or Part D-reimbursed pharmacies overlapped by 7 or more days, a time period used previously to assess medication overlap.26 We assessed whether a veteran had an overlap of medication supplies from VA or community-based pharmacies of 7 days or more as a dichotomous variable .To assess the association of Blue Button medication view use with obtaining medications from VA and community-based pharmacies with days supply from the same drug class that had overlap by 7 or more days, we used multivariable logistic regression analysis with double-robust estimation.26 Additionally, we determined the proportion of veterans in each group with 7 or more days supply overlap from the same drug class. We compared these proportions between the user and the nonuser groups overall and by decile of the number of 30-day supplies of medications that veterans obtained.With double-robust estimation, the logistic regression model included covariates and was estimated with inverse probability weighting as previously described. Results will be unbiased with double-robust estimation if either the propensity score or outcome (in this case logistic regression) model are specified correctly.There were 73,958 veterans who met the study inclusion and exclusion criteria: 7,973 were Blue Button medication view users, and 65,985 were nonusers. P < 0.001; P < 0.001). Combining VA and Medicare Part D-reimbursed pharmacies, users obtained on average (SD) 152.1 (106.0) total 30-day medication supplies; nonusers obtained, on average, 71.3 (49.1) total 30-day supplies (P < 0.001).During the 12-month period following the index date, users obtained on average (SD) 135.3 (108.4) 30-day supplies of medications from VA pharmacies, whereas nonusers obtained on average 41.9 (46.6) 30-day supplies of medications from VA pharmacies . On average, 49.0% of these classes (5.1/10.4) were from VA pharmacies only; 43.3% (4.5/10.4) were from non-VA pharmacies only; and 9.6% (1.0/10.4) classes were from both VA and non-VA pharmacies.Users obtained medications from an average (SD) of 12.0 (6.3) different VA drug classes. On average, 69.2% of these classes (8.3/12) were from VA pharmacies only; 22.5% (2.7/12) were from Part D-reimbursed pharmacies only; and 6.7% (0.8/12) classes were from both VA and Part D-reimbursed pharmacies . In compP < 0.001). However, the percentage of patients with overlap varied by the total number of 30-day supplies of medications that a veteran obtained. In P = 0.05); for veterans with more than 153 thirty-day supplies, the percentage of users with overlapping days supply of medication was 12 percentage points lower than for nonusers .For veterans with 82-96 thirty-day supplies, the percentage of users with overlapping days supply of medication was 4 percentage points lower than for nonusers , controlling for the number of 30-day supplies of medications that veterans received. Other characteristics associated with greater odds of having overlapping days supply of drug classes from VA and Part D-reimbursed pharmacies included age more than 45 years, living in an urban area, living further from a VA facility, and obtaining a larger number of 30-day supplies from VA pharmacies.Results from the double-robust estimation in The top drug classes for which the days supply from VA and non-VA pharmacies overlapped by 7 or more days are presented in eVet, this was because these users tended to have a higher number of prescriptions to fill.Veterans who were using the Blue Button medication view feature of the VA’s personal health record portal My HealtheVet obtained over 3 times the number of 30-day supplies of medications from VA pharmacies and over twice the number of total 30-day supplies from all sources  as nonusers. Nearly a third of users and nearly a quarter of nonusers obtained prescriptions with overlapping days supply of 7 or more days for medications from the same drug classes from both VA and Part D-reimbursed pharmacies. Although the overall percentage of veterans with overlapping days supply was significantly larger for veterans who used the Blue Button medication view feature of My HealtheVet’s health information management and communication features may be especially attractive to patients who are managing complex chronic diseases, and those managing multiple medications may be more likely to adopt the portal because of the convenience of online prescription refills and the Blue Button medication view feature.My HealthThe percentage of veterans with overlapping days supply from the same drug classes varied by the total number of 30-day supplies that veterans obtained. Among veterans with a need for a greater number of 30-day supplies of medications, the percentage with overlapping days supply was lower for veterans who used the Blue Button medication view feature than for nonusers. Moreover, adjusting for the number of medication supplies, the odds of obtaining overlapping days supply was over 18% lower for users.These findings highlight that a substantial portion of veterans receive medications with overlapping days supply from the same drug classes from both VA and non-VA pharmacies. However, among higher medication users, use of the Blue Button medication view feature of the VA’s personal health record portal was associated with less polypharmacy compared with veterans who had not signed up to use the VA’s personal record portal. Consequently, it might be useful for prescribers to encourage their patients who are obtaining larger numbers of medications to use the Blue Button medication view feature of My HealtheVet to assist with management of their prescription medications.28; however, patients remain the most important source of information about all medications that they are taking. This necessitates additional investigation and communication between providers and patients to ensure optimal medication reconciliation and continuity of care.For patients acquiring their medications from VA and non-VA pharmacies, the VA may have limited information of the patients’ non-VA medications. Efforts are underway to enhance information sharing across VA and non-VA settingsThis communication is particularly important because situations in which providers in one health care system do not know about medications prescribed by providers in another health care system may pose a safety risk, which is compounded by this study’s finding that some of the medications with overlapping days supply from VA and Part D-reimbursed pharmacies are drugs that can be dangerous if not used correctly. For example, among the 10 most frequent drug classes with overlapping days supply are opioid analgesics for which patients are at high risk of death secondary to opioid overdose.29 Use of the Blue Button medication view feature of the personal health record portal may enhance medication reconciliation and information sharing across health care systems, which may be warranted, since multiple previous studies have shown possible associations between dual health system use among veterans and increased morbidity and mortality.33 It should be noted that the Blue Button medication view includes only VA prescriptions and the non-VA medications that veterans self-enter into their personal health records, which may differ from the non-VA medication list in the VA’s electronic medical record. However, efforts are underway to make the non-VA medication list available in the patient portal too.There is limited information on medication reconciliation across health systems. One review suggests that medication reconciliation within health systems has the potential to identify many medication discrepancies and reduce potential harm.eVet—increased their ability to have an accurate medication list and assisted in making medication treatment decisions.16 Moreover, 50% reported that they did not order a laboratory test or another procedure because of information in the Continuity of Care document.16Results from previous studies assessing the potential for My HealtheVet to decrease duplication of services suggest that use of the Blue Button medication view feature might facilitate information sharing across health care systems. In an interventional study, 90% of providers stated that the Continuity of Care document—a standardized electronic file containing a VA health summary report that patients can share with health care providers available through the Blue Button feature of My Health18 Although not all veterans will download health care data and share it with their health care providers, a tool such as the VA Blue Button medication view feature of My HealtheVet may complement provider-mediated health information exchange until health care systems are designed to allow providers in different organizations to access key information, such as medications, across health care systems.In another study , veterans who were trained to share their Continuity of Care documents with non-VA providers had significantly fewer duplicate laboratory tests than the control group.There were limitations to these analyses. We only examined non-VA pharmacy data for veterans enrolled in Medicare Part D. Private-sector data were not available for medications that were not reimbursed by a Part D prescription plan. Consequently, our results provide a lower bound estimate of the percentage of VA enrollees who have overlapping medications from VA and non-VA pharmacies.There may be multiple approaches to assessing misuse of medications. In this study, we focused on a potential issue  that could arise when veterans are obtaining medications from VA pharmacies and community-based pharmacies that are covered by the Medicare Part D drug benefit. Additionally, the Blue Button medication view includes VA medications but only non-VA medications that veterans have self-entered into their personal health records. The non-VA medication list in the VA electronic medical record may differ from the Blue Button non-VA medication list. The effect of this potential inconsistency is uncertain.It should also be noted that ZIP codes were used to determine rural/urban status, but a veteran may have relocated during the study period. We used the HCC risk score to estimate overall health status of veterans; however, this health status may change over time.eVet features , reduced medication overlap could be a result of these services, as well.There may be different implications from overlapping days supply due to the same drug vs overlap due to a physician-directed change in treatment. However, we were unable to make this source distinction from our data. Moreover, because the viewing of the medication is highly likely to be correlated with other My HealtheVet may be different from those not using the feature because of unobservable factors .17Tying polypharmacy to adverse drug events was beyond the scope of this study; however, we recognize that this would be an important topic for future research. In addition, veterans using the Blue Button medication view feature of My HealthVeterans who used the Blue Button medication view feature of My HealtheVet obtained a larger number of 30-day supplies of medications from VA pharmacies than nonusers. For veterans who obtained a larger number of 30-day supplies of medications, use of the Blue Button medication view feature of My HealtheVet was associated with less overlap in days supply of medication from the same drug class from VA and Part D-reimbursed pharmacies than for nonusers. These results highlight the importance of sharing information and the need to educate patients about communicating with VA and non-VA providers about their medications.


Breast cancer, the most common malignant cancer in women worldwide, is typically diagnosed by x-ray mammography, which is an unpleasant procedure, has low sensitivity in women with dense breasts, and involves ionizing radiation. Breast magnetic resonance imaging (MRI) is the most sensitive imaging modality and works without ionizing radiation, but is currently constrained to the prone imaging position due to suboptimal hardware, therefore hampering the clinical workflow.The aim of this work is to improve image quality in breast MRI, to simplify the clinical workflow, shorten measurement time, and achieve consistency in breast shape with other procedures such as ultrasound, surgery, and radiation therapy.To this end, we propose “panoramic breast MRI”—an approach combining a wearable radiofrequency coil for 3 T breast MRI (the “BraCoil”), acquisition in the supine position, and a panoramic visualization of the images. We demonstrate the potential of panoramic breast MRI in a pilot study on 12 healthy volunteers and 1 patient, and compare it to the state of the art.With the BraCoil, we demonstrate up to 3-fold signal-to-noise ratio compared with clinical standard coils and acceleration factors up to 6 × 4. Panoramic visualization of supine breast images reduces the number of slices to be viewed by a factor of 2–4.Panoramic breast MRI allows for high-quality diagnostic imaging and facilitated correlation to other diagnostic and interventional procedures. The developed wearable radiofrequency coil in combination with dedicated image processing has the potential to improve patient comfort while enabling more time-efficient breast MRI compared with clinical coils. As a result, approximately every second woman undergoes imaging, which is not well suited to her anatomy.6 X-ray–based screening is not recommended below the age of 45 years in most national screening programs7 due to the risks of ionizing radiation together with lower incidence rates and lower diagnostic performance due to a higher proportion of women with dense breasts. In addition, DM requires breast compression, causing discomfort or pain and can consequently reduce attendance rates.8Digital x-ray mammography (DM) is the standard screening modality due to its procedural simplicity, accessibility, and proven effectiveness regarding patient outcomes.10—independent of breast density.11 Breast MRI examinations commonly involve the intravenous administration of gadolinium-based contrast agents to evaluate tumor vascularization. Contrast-enhanced breast MRI can reliably distinguish between benign and malignant breast lesions.13 In addition, the imaging method has been shown to be the superior assessment modality for early detection of breast cancer, both in women with high risk of breast cancer and very dense breasts,17 and was recently suggested for tailored screening.9The limitations of x-ray–based breast imaging modalities can be alleviated by the use of magnetic resonance imaging (MRI) as it does not rely on ionizing radiation, yields excellent soft tissue contrast, and has the highest sensitivity for detection of breast cancerTypically, breast MRI is performed with the patient lying on her front (prone) with exposed breasts hanging into cup-shaped molds of a rigid radiofrequency (RF) coil. This current clinical setup does not exploit the full potential of breast MRI for the following reasons:19 whereas acquisition in the supine position facilitates image fusion22 and tumor localization during US-guided biopsy, surgery, or radiation therapy.23 In addition, the prone posture is uncomfortable for the patient, and the lack of physical support of the hanging breasts may lead to motion artifacts, which compromise image quality.24 The feasibility of performing breast MRI in the supine position has been demonstrated.18 These arguments call for a new methodological approach enabling supine breast MRI.First, due to gravitational breast tissue deformation in the prone position, diagnosis and treatment are complicated since the breast shape differs considerably from the posture in supine ultrasound (US) or surgery,27 to flexible,29 and even stretchable coils.33 A flexible coil vest prototype for supine breast MRI has recently been briefly presented,34 but not described or tested in detail. Coaxial transmission line resonators  with 1 gap in the inner and outer conductor of a coaxial cable were already described in 194635 and the idea to use them as flexible receive coils for MRI dates back to Zabel et al.36 Based on several recent studies39 characterizing coaxial coils, the potential of this technology for flexible coil design has been reconsidered by the community.42 Radiofrequency coils suitable for supine breast MRI are either semiflexible  or fully flexible coils . Although some of these coils allow for proof-of-concept supine breast MRI, they are not optimized for breast MRI leading to low SNR, potentially unwanted aliasing artifacts and practical restrictions. Therefore, a flexible coil for supine breast MRI, overcoming the limitations of existing research prototypes and product coils, is needed.Second, standard coils for (prone) breast MRI are designed to accommodate rather large breasts, which leads to reduced signal-to-noise ratio (SNR) for small breasts and precludes the measurement of very large breasts. Radiofrequency coils that can be form-fitted to the anatomical region of interest have been in the focus of recent developments. In particular, when the anatomical intersubject variability is high, as it is the case with the female breast, they can be better adapted to the subject's shape and thereby achieve higher SNR. Existing approaches and research prototypes range from rigid-adjustableThird, prone breast images are conventionally displayed upside down in an axial Cartesian view. However, for supine imaging, this view is suboptimal, since the breast tissue is flattened and distributed over the chest wall making the axial cross-section of the breast considerably thinner. A coronal view may be more suited for supine images, but is still not optimal for viewing the lateral parts of the breasts. In both cases, the high number of slices leads to long reading times. Consequently, a new visualization paradigm for supine breast MRI is required.44 and has benefits, especially for imaging techniques such as DWI.45 The BraCoil is designed to strongly improve comfort, enable consistency in the breast shape with other imaging and therapeutic modalities, reduce preparation and acquisition time, and increase SNR. In addition, we introduce a panoramic visualization of both breasts similar to dental panoramic x-ray, overcoming the limitations of the Cartesian view in supine breast MRI. We validate the panoramic breast MRI approach in a healthy volunteer study against 2 commercial coils and demonstrate the fundamental aptitude of this technique for clinical assessment in an exemplary case of a breast cancer patient.All these issues underline the necessity of technical advancements in dedicated hardware and image processing for supine breast MRI. In this work we, therefore, propose “panoramic breast MRI,” which stands for the combination of a wearable RF coil, supine acquisition, and a panoramic visualization of breast MR images. We present and characterize the “BraCoil,” a flexible, vest-like receive-only coil array made of coaxial coil elements for 3 T MRI that can be used both in supine and prone positioning. The coil was developed for 3 T MRI, since the higher achievable SNR compared with lower field strength allows for acquisitions with higher in-plane resolution and/or thinner slices, which can improve the detection of small lesions in the breast47 to accommodate a large range of body shapes and breast sizes while sufficiently covering both breasts and allowing for assessment of the axillary lymph nodes.A flexible breast coil array that can be worn like a sports bra was conceived and implemented. The shape of the textile parts of the vest and the matching coil array layout were developed based on prior consultation of experienced breast radiologists and population statistics2 with the sensitive imaging area exceeding the array size at all sides. Each module contains 4 circular, single-gap coaxial coils of 8 cm diameter made from thin and very flexible coaxial cable with an interruption (gap) in both inner and outer conductor to achieve self-resonance close to the Larmor frequency of 123.2 MHz for a 3 T MR scanner . The electrical circuit schematic for a single coaxial coil's interfacing to the MR scanner is sketched in the supplementary material . In contrast to another design,34 the BraCoil's layout is confined to expected regions of breast tissue, and thereby avoids potential fold-over artifacts from the abdomen and unnecessary hardware and weight.The resulting design Fig. A is a flhttp://links.lww.com/RLI/A818). Bench and phantom MR tests for coil characterization and patient safety testing were performed before volunteer and patient measurements .The vest can be adjusted to the subject's contours with waist and shoulder belts to ensure a tight fit and optimize the achievable SNR. Thanks to the small weight of ≈1.5 kg distributed on the subject , the array can be worn comfortably in supine position  following the Declaration of Helsinki of 1975, and volunteers as well as the patient included in this study declared informed consent. The clinical investigation according to Regulation (EU) 2017/745 Article 62 was approved by the Austrian Federal Office for Safety in Health Care. The BraCoil is an investigational device and has neither FDA approval nor CE marking.2, age 31 ± 5  years, and bra sizes ranging from 70A to 90D, which corresponds to breast volumes ranging from 495 mL to 3020 mL. Bra sizes are indicated according to the Joint European standard for size labeling of clothes (EN13402). The sample size was chosen on the basis of a desired measurable difference by a factor of 1.2 between the BraCoil and reference coil's SNR . Using a power of 0.8 and significance level α of 0.05 together with an estimated 20% dropout rate, a sample size of 10 was set as the minimum requirement for our study. The prospectively defined inclusion criteria for volunteers were female sex, age between 19 and 80 years, and a breast size between 70A and 90D, which can be considered representative for a larger population.47 To demonstrate the suitability of the BraCoil for breast cancer assessment, a 26-year-old female patient with a suspected breast lesion assigned BI-RADS 4, body mass index of 26 kg/m2, and bra size of 85E  was included in this study.The study population consisted of 12 healthy female volunteers with mean body mass index 23 ± 4  kg/mHealthy volunteers were measured with the BraCoil and 2 reference product coils in a chronologically randomized order: a dedicated breast coil “16-channel Sentinelle Breast Coil” (reference coil Ref1) and a semiflexible 18-channel multipurpose coil “Body 18” (reference coil Ref2) . The patient was measured with the BraCoil and reference coil Ref1. One measurement session was performed per volunteer/patient and per coil.To assess the preparation times required with the BraCoil in comparison to Ref1, an operator experienced with both coils repeated the coil setup on the patient table and patient positioning 5 times. The same experiment was performed with 2 experienced operators working together. In addition, an inexperienced user only familiar with the use of head coils performed the coil setup and positioning 3 times to evaluate the learning curve.R, and by the so-called geometry-factor (or short “g-factor”48), which is dependent on the correlation of signals between the individual coil channels and is spatially variable. Thus, another end point of this study were g-factor maps in a coronal slice with acceleration in left-right and head-foot direction. The number of slices containing breast tissue with and without panoramic reconstruction was evaluated.Prospectively selected end points for which MR data were collected were mean SNR and SNR homogeneity in the breast volume. With parallel imaging, the SNR is decreased by the square root of the acceleration factor g-factors <2) due to the high channel count of the BraCoil, and a reduction of the overall number of slices to read after panoramic reconstruction as compared with a Cartesian axial or coronal view.The overall purpose of this study was to evaluate the BraCoil's MR and bench performance and combine novel hardware with efficient panoramic reconstruction methods. Prespecified research hypotheses or objectives were as follows: equal or increased mean SNR and SNR homogeneity in the breast volume compared with clinical standard reference products, high acceleration possibilities . The BraCoil's performance was compared with reference coils Ref1 and Ref2. Two subject positioning variants—supine and prone—were tested with the BraCoil and Ref2. For the measurements in prone position with the BraCoil, a simple plate with holes on the patient bed was used to accommodate the module housings. Ref1 only allows for imaging with the subject in prone position. All supine measurements were acquired with volunteers and a compliant patient briefed to perform abdominal breathing rather than chest breathing to limit motion artifacts.http://links.lww.com/RLI/A820).Magnetic resonance sequence parameters used for the technical coil performance evaluation conducted with the healthy volunteer group and the multiparametric clinical protocol, which was tested on volunteers and finally used for the patient measurement are listed in the supplementary material  acquisition to assess the coils' sensitive area. For SNR evaluation, a T1-weighted 3D gradient echo (GRE) sequence with low contrast between fat and water was chosen. To this end, the flip angle was adapted so that the MR signals originating from fat and water were similar in amplitude. For g-factor calculation T1-weighted 2D GRE scans of a few relevant coronal slices through the breast were acquired with the BraCoil in prone subject position. A noise-only scan (without RF transmit pulse) was acquired to obtain the noise correlation matrix used for SNR calculations.The technical protocol included a T1-weighted fast low angle shot  and a standard clinical protocol using Ref1 (prone). During the patient examination, dynamic contrast-enhanced T1-weighted imaging with fat suppression was performed. The gadolinium-based contrast agent used was 0.1 mmol/kg body weight of Dotarem . While with the BraCoil, 1 native and 7 fast T1-weighted scans were acquired within approximately 5.5 minutes (pause for contrast agent administration excluded); with Ref1, 1 native and only 4 postcontrast T1-weighted scans were acquired within the same scan time.The clinical protocol consisted of a high resolution and a fast dynamic T1-weighted 3D FLASH acquisition with spectrally attenuated inversion recovery (SPAIR) fat suppression, a T2-weighted turbo spin echo scan and a diffusion-weighted imaging (DWI) RESOLVE51 Further, noise-only data were used to calculate the normalized noise correlation matrix for the smallest , a medium-sized , and the largest  subject .Three-dimensional SNR maps for a nonaccelerated acquisition, that is, fully encoded k-space matrix, were calculated offline in MATLAB 2021b  from GRE imaging data and noise-only scans using the pseudo multiple replica method.54). The mean 3D SNR achieved with the BraCoil and the reference coils was compared using single-sided paired t tests.The mean 3D SNR was evaluated in a manually segmented region of interest (ROI) covering the entire breast tissue for all 5 measured setups  using open-source image processing software .Relative SNR homogeneity was assessed as the standard deviation divided by the mean SNR over the segmented breast volumes. The results for all subjects were compared between the different coil and positioning setups by single-sided paired g-factor maps with simulated acceleration factors of R = 2, 4, 6, and 8 in left-right (LR) and head-foot (HF) direction using open source Matlab code56 also based on the pseudo multiple replica method. Resulting g-factor maps were plotted in a coronal slice for 3 differently sized breasts.To investigate the BraCoil's parallel imaging performance, we additionally calculated 2D SNR and 54 to reconstruct panoramic breast images:Since the breast tissue is distributed along the curved shape of the thorax when lying in the supine position, we hypothesize that displaying the images along the shape of the thorax rather than in Cartesian axial or coronal slice direction could be beneficial. We expect that such a “panoramic” visualization would lead to more breast tissue visible in each slice, thereby reducing the number of slices containing breast tissue. In addition, we believe that the panoramic view could be an intuitive new approach for assessing the anatomy and relative position of image features. Therefore, panoramic breast images were created by using 2 consecutive curved planar reformatting transforms along the sternum and along the breast shape in the axial view, respectively  and the patient data were created according to the workflow above.To quantify the effect of the panoramic breast view, the total number of image slices comprising breast tissue was compared between supine BraCoil acquisitions in panoramic/axial/coronal view and prone acquisitions with Ref1 in axial view. To this end, the breast tissue segmentations used for SNR calculation were transformed into the panoramic view. The volumes were then tightly cropped to the extent of the breast tissue with more than 10 breast tissue voxels. The sizes of the remaining volumes in HF and AP direction were measured, and the relative size reductions of the flattened volume to the references were calculated.http://links.lww.com/RLI/A821). From S-parameter measurements, coil impedance matching to 50 Ω and coupling between channels were determined for the smallest, the medium sized, and the largest subject within the cohort. Globally, matching (Sii) was better than −10 dB for all channels and subjects. Averaged over all channels, matching was −18.6 dB/−18.5 dB/−16.9 dB for the smallest, the medium, and the largest subject, respectively. The corresponding interelement coupling (Sij) was below −12.4 dB/−11.7 dB/−12.3 dB. The normalized noise correlation was between 6% and 7% on average. These bench values indicate proper implementation and functioning of the coil array.The scattering (S-) parameter and the normalized noise correlation matrix were measured and are displayed in the supplementary material , with a particular benefit for smaller breasts. The SNR gain over the standard breast coil Ref1 ranges from almost 3-fold SNR in the smallest breasts to equal SNR in the largest breasts. The SNR gain over the semiflexible coil Ref2 is roughly constant with an average of ≈1.7, that is, +70%.The results of the SNR comparison are shown in Figure http://links.lww.com/RLI/A822).Because of the nature of surface coils, the BraCoil's SNR rapidly decreases with distance to the coil elements; therefore, the relative SNR homogeneity within the breast volume was compared with the reference coils for all subjects of the study cohort. The homogeneity of the BraCoil is not significantly different from the clinical standard coil Ref1  and 6 in head-foot (HF) direction are shown in Figure http://links.lww.com/RLI/A823). The maximum acceleration factor with g-factors <2, which can be considered reasonable, was determined as 6 × 4 = 24. The higher value in LR direction is in agreement with the higher channel count of the coil array in that direction.The high SNR and high channel count of the BraCoil can be used to accelerate image acquisition by using parallel imaging techniques. Maps of http://links.lww.com/RLI/A824). For experienced operators, preparation times with the BraCoil are approximately 1 minute shorter than with Ref1. An inexperienced operator achieved the same preparation time in the third run of setting up the BraCoil. In addition, coil setup is easily achievable with only 1 operator with the BraCoil, whereas Ref1 may require 2 operators to lift the heavy and large coil onto the patient table.The results of the evaluation of preparation times are summarized in the supplemental material  on the MR scanner console, robust techniques for intensity correctiong-factors below 2, which will be advantageous to accelerate the current clinical imaging protocol while conserving high SNR. Alternatively, one could keep standard examination times but add highly specific pulse sequences, for example, high-resolution DWI, which are currently often left out due to long scan times and the related high examination cost. Further, simultaneous multislice imaging techniques, particularly in 2D imaging sequences such as T2-weighted imaging and DWI, would benefit from the BraCoil's low g-factors in both left-right and head-foot direction. Therefore, pulse sequence protocols tailored to the strengths of the BraCoil will need to be further developed to exploit its full potential.The BraCoil enables acceleration factors of up to 6 × 4 with The supine positioning enabled by the BraCoil can bring significant advantages regarding patient comfort, coil usability, and similarity of the breast shape to other modalities. A quantitative evaluation of patient comfort by means of a questionnaire after breast MRI examinations using the clinical breast coil and the BraCoil is part of an ongoing study. To date, the sample size of study participants is still too low to report conclusions. However, qualitative feedback received by all volunteers in our study revealed that they subjectively preferred the examination using the novel flexible coil in supine (or even in prone) position over standard clinical prone breast MRI. Further, in future investigations, feedback from technologists preparing the MRI setup and executing the examination will be collected. Preliminary data suggest that preparation times with the BraCoil are shorter than with the clinical reference coil and the setup can easily be performed with a single operator.60 in the presented study, it was of little concern in healthy volunteers, since they were instructed to perform abdominal breathing to minimize chest movement. However, motion issues clearly need to be addressed in patients, as they are in a much more stressful situation. A potential solution to enable free breathing examinations would be expiratory gating with navigators61 or a respiratory detection device, combined with phase-encode reordering,62 which, however, comes at the cost of longer acquisition times. A promising alternative could be to equip the coil with on-board motion sensors64 or other motion-sensitive technology65 combined with online retrospective motion correction techniques.66As highlighted by the clinical showcase, supine acquisition with the BraCoil can improve lesion localization and facilitate second look US and US-guided biopsy, and, hence, reduce the number of costly MR-guided biopsies. However, lying on the back entails challenges such as motion of the patient's chest due to breathing. In addition, while the positioning is similar to breast US or the surgical table and, thus, would improve translation of imaging findings into targeted biopsies and precise surgery, the breast is less extended so that the exact localization of lesions and their relation with anatomical structures such as the nipple line may be more difficult to assess. Whether the supine position is more susceptible to gross motion of the breasts and would, for example, make follow-up examinations or the assessment of imaging features (lesion margins and heterogeneity) more difficult is subject to future investigation. Although breathing induced motion artifacts can deteriorate image quality,The prone position with the BraCoil yields very similar SNR compared with the supine measurement and avoids motion issues since the breasts are not moving with respiration in that case. The breast shape in this setup Fig.  can be i67 The technical refinement of the panoramic viewing technique is an open task, which can be addressed in the near future. Also, it is not obvious that a reduction in the number of slices with a panoramic view directly leads to shortened image interpretation times. Therefore, in future studies, we will monitor reading times of radiologists with different levels of expertise and collect their feedback regarding image quality ratings and general acceptance of the panoramic breast view in practice. Other aspects that will require a long-term investigation in the future are repeatability studies and the evaluation of the novel breast MRI technique in suitable larger patient cohorts, for example, for general breast assessment, surgery planning, or breast cancer screening.The proposed panoramic breast view reduced the number of slices to be read by a factor of 2–4 compared with the Cartesian view. Currently, it still requires manual interaction for drawing 2 curves across the breast and along the sternum, which should be automated in the future. Also, since the flattening of the breast is based only on these 2 lines, the flattening algorithm becomes less accurate toward the corners of the panoramic image. This shortcoming could be addressed by reformatting the images along a 3D curved manifold following the shape of the chest wall as suggested in reference.68 and MR-based screening.69Panoramic breast MRI together with dedicated visualization tools for diagnosis, radiation therapy and surgery planning, and artificial intelligence for lesion detection and classification, could achieve a level of diagnostic performance that would enable contrast-agent free breast examinations for assessmentAlthough the clinical impact of the presented approach is yet to be demonstrated and is subject of ongoing research, we envision that panoramic breast MRI will improve cost-effectiveness, simplify the translation of diagnostic information from imaging into clinical decision making for a more personalized treatment, and will ultimately improve patient outcomes.


MSM/Ms mouse derived from the Japanese wild mouse has unique characteristics compared to the widely used C57BL/6 mouse. To examine the usefulness of the MSM/Ms mouse for the comparative genomic analysis, expression of small RNAs were analyzed by the large-scale sequence analysis for two strains of mouse, C57BL/6 and MSM/Ms. As a trial, expression of box C/D snoRNAs, which are the most abundant small RNAs in the cell, were analyzed. By the comparison of the read number for each fragment, 11 snoRNAs with single nucleotide polymorphisms (SNPs) were detected. One of the snoRNAs, SNORD53, shows the expression only for MSM/Ms and this snoRNA has a mutation in the box sequence in C57BL/6. Thus, it was demonstrated that the proposed experimental system using SNPs can give new insight for the gene expression regulation. Mus musculus), C57BL/6 mouse (B6) has been one of the most popular strains used in a variety of research fields [Among the experimental mouse strains  were found during an analysis of transcription from the sense–antisense transcripts (SAT) loci , 14. TheIn the present study, we focused on the expression of small nucleolar RNAs (snoRNAs) as a trial expression analysis because these are the most abundant small RNAs in cells. There are two types of snoRNA, C/D box snoRNA (SNORD) and H/ACA box snoRNA (SNORA), where SNORD forms a loose stem-loop and SNORA forms a tight two-hairpin structure . Many snTo analyze small RNAs, we performed the next generation sequencing (NGS) analysis of small RNA fractions to find several novel structured small RNAs from the brain of B6 . In the RNAs were extracted from male mouse  and MSM/Ms  brain by using TRIzol reagent (Invitrogen) according to the manufacturer’s protocol. Brains from typically two mice were homogenized for each subspecies before RNA extractions. Total RNA (60 μg) was then separated by 12% polyacrylamide/7M urea denaturing gel electrophoresis. The gel was stained with ethidium bromide and irradiated with UV light to detect RNA bands. Small RNAs of about 40 to 140 nt in length were recovered from the gel to obtain 2.2 and 3.2 μg/μl samples for B6 and MSM, respectively. Mouse experiments were performed in accordance with the institutional guidelines of Chiba Institute of Technology and Kochi University, and approved by the Animal Care and Use committees of both institutions under the approval numbers of 18002 and J-00022, respectively. The mice were properly sacrificed by cervical dislocation.DNA libraries for sequencing were prepared with three kinds of preparation kits; TruSeq Small RNA Library Prep Kit  , NEBNexthttps://genome.ucsc.edu) or subjected to the BLAST search in the snoRNA orthological gene database snOPY [The obtained RNA sequences in length of 10–292 were processed by mainly Microsoft Excel and home-made programs in part. Sequences for mouse brains of B6 and MSM were compared to each other and the sequences with more than 100-fold change between MSM and B6 or more than 100 for one strain and 0 for the other strain in read number per million total read number (rpm) were selected. Each sequence was mapped on the mouse genome (GRCm39/mm39) using BLAT in UCSC Genome Browser  as gene clusters . AlthougIn the present study, most of SNPs were located neither on the box sequences nor complementary sequences for the target RNAs , suggestIn this study, differential expressions between two mouse strains, B6 and MSM, of box C/D snoRNA were analyzed by the large-scale sequence analysis. In most cases, differential expressions were found to be due to SNPs rather than different regulation of gene expression. In most cases, no SNPs were found in functional sequences such as the box sequences or the complementary sequences to target RNAs. As described below, SNORD53 was identified only for MSM, indicating that SNP-based analysis is effective for the analysis of differential expressions between strains. Thus, it was demonstrated that the comparison between the two strains give new insight for the gene expression regulation. It should be noted that SNORD115 and SNORD116, which form large gene clusters, are also basically distinguishable by SNPs despite the polymorphisms in these loci. For SNORD115 as example, B6-1 to 5 are B6 specific and MSM-1 and 2 are MSM specific as shown in Expression of SNORD53 may be different between the two strains; this snoRNA was found only for MSM. In fact, the sequence of SNORD53 was extracted from the three data for B6 to find negligible read numbers . Because SNORD53 in B6 has a mutation in the box sequences and this may cause the gene silencing or degradation of the product. Thus, it was demonstrated that the comparison between the two strains give new insight for the gene expression regulation. Because the genome sequence of MSM has been determined, it is possible to identify snoRNAs with SNPs. However, the method in this study can show the existence of SNPs and expression levels simultaneously. In addition, this method can be applied to strains for which the genome sequence is not determined. Further analysis will give more information on the differential expression of small RNAs.As shown in Some snoRNAs are located at the imprinted loci and are affected by the expression mechanism of the imprinted gene . It is kAll mammals, including human, inherit a set of chromosomes from father and mother, and both parents-derived genes are expressed . HoweverS1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.


Vascular services in England are organized into regional hub-and-spoke models, with hubs performing arterial surgery. This study examined time to revascularization for chronic limb-threatening ischaemia (CLTI) within and across different care pathways, and its association with postrevascularization outcomes.Three inpatient and four outpatient care pathways were identified for patients with CLTI undergoing revascularization between April 2015 and March 2019 using Hospital Episode Statistics data. Differences in times from presentation to revascularization across care pathways were analysed using Cox regression. The relationship between postoperative outcomes and time to revascularization was evaluated by logistic regression.versus 12 (7–19) days; P < 0.001). Shorter times to revascularization were also observed for patients presenting to outpatient clinics at arterial hubs compared with spoke hospitals (13 (6–25) versus 26 (15–35) days; P < 0.001). Within most care pathways, longer delays to revascularizsation were associated with increased risks of postoperative major amputation and in-hospital death, but the effect of delay differed across pathways.Among 16 483 patients with CLTI, 9470 had pathways starting with admission to a hub or spoke hospital, whereas 7013 (42.5 per cent) were first seen at outpatient visits. Among the inpatient pathways, patients admitted to arterial hubs had shorter times to revascularization than those admitted to spoke hospitals (median 5 (i.q.r. 2–10) For patients with CLTI, time to revascularization was influenced by presentation to an arterial hub or spoke hospital. Generally, longer delays to revascularization were associated with worse outcomes, but the impact of delay differed across pathways. This study examined time to revascularization from presentation for patients with chronic limb-threatening ischaemia (CLTI) within and across different care pathways within the reginal hub-and-spoke models of vascular service networks, using Hospital Episode Statistics data between April 2015 and March 2019. The data suggested that, among the patients with CLTI, time to revascularization was influenced by presentation to an arterial hub or spoke hospital. This study also suggested that, generally, longer delays to revascularization were associated with worse postrevascularization outcomes of major amputation and in-hospital death, but the impact of delay differed across care pathways. The symptoms result from reduced blood flow in the legs, and revascularization is required to improve blood flow and reduce the risk of limb loss. Revascularization may be performed using either endovascular techniques (angioplasty and/or stenting), open surgery  or a hybrid combination of procedures, depending on the patient’s risk, severity of limb threatening ischaemia, and anatomical patterns of disease1–4.Chronic limb-threatening ischaemia (CLTI) is a severe form of peripheral arterial disease (PAD) in the lower limbs characterized by rest pain and/or tissue loss, such as ulceration or gangrene (Fontaine classification III or IV)6. In response to the evidence that greater surgeon and vascular unit volumes improve patient outcomes7–9, there has been a centralization of vascular arterial surgical services in the National Health Service (NHS)10, with a hub-and-spoke model11 introduced within geographical regions. In these regional vascular networks, arterial hubs provide arterial surgery and complex endovascular interventions. Non-arterial spoke hospitals provide outpatient services including local assessment and diagnostic services, and, where appropriate, day-case peripheral angioplasty and stenting10. Patients admitted to a non-arterial spoke hospital are transferred to the regional vascular arterial hub when they require an operative procedure12. Through reconfiguration, the number of NHS acute Trusts that perform lower limb bypass operations in England fell from 110 in 201113 to 70 in 201714.Centralization has been a common strategy for highly specialized surgery in healthcare systems in Europe and North America15. National guidance from the Vascular Society in the Provision of Vascular Services 2018 (POVS 2018)10 and the Peripheral Arterial Disease Quality Improvement Framework (PAD QIF) in 201916 recommends revascularization within 5 days of hospital admission for patients with severe CLTI, or within 14 days of outpatient referral for those who present with stable disease. To ensure patients have rapid access to both endovascular and surgical revascularization, vascular networks need to have effective referral pathways. Failure to achieve this could result in extended delays, particularly for patients who first present at a spoke hospital before having revascularization at an arterial centre. The POVS 2018 guidance10 states that ‘equal access to treatment should occur irrespective of where in the network a patient presents’. Therefore, the aim of this study was to examine how time to revascularization for patients with CLTI might vary depending on their care pathway across NHS hospitals in England. This study also investigated the impact of time to revascularization on adverse short-term outcomes, including in-hospital mortality and the risk of subsequent major lower limb amputation during the same admission following revascularization.There has been a long-standing concern that late presentation and delayed management of CLTI contributes to increased rates of lower limb amputation and mortalityTable S1) to a NHS hospital in England for a lower limb revascularization procedure (codes listed in Table S2) between 1 April 2015 and 31 March 2019. Because patients who had previous revascularization procedures may have followed different care pathways with potentially more adverse outcomes, only the first revascularization procedure for each patient was included. Patients were excluded if they had other lower limb revascularization procedures recorded within 2 years before the start of the study interval (1 April 2015). The OPCS procedure codes were used to distinguish between endovascular (angioplasty/stent), open (bypass/endarterectomy), and hybrid procedures. A hybrid procedure was recorded where both endovascular and open surgical operations were performed on the same date. Patients with end-stage renal disease and on dialysis were excluded, because special care might be required to accommodate their dialysis requirements and potentially prolong waiting times to revascularization. Patients who had both revascularization and major amputation on the date of the first lower limb procedure were defined as those undergoing a primary amputation and also excluded. The analysis was restricted to NHS hospitals in England which had not changed their status from an arterial centre (hub) to a non-arterial centre (spoke) during the study interval as a result of reconfiguration of vascular services, and to patients who resided in England at the time of revascularization.The study used a data set extracted from the inpatient Hospital Episode Statistics (HES) database held by NHS England. The inpatient database codes diagnostic information using ICD-10, and operative procedures using OPCS-4. The study cohort consisted of patients aged 35 years and over, admitted as an emergency with CLTI-related diagnostic codes , or referred to an outpatient clinic for specialist assessment before a treatment decision was made (outpatient pathway). The first contact with vascular services preceding revascularization was identified using patient records from both inpatient and outpatient HES data sets. When patients had an outpatient visit with a specialist in vascular surgery, diabetic medicine, podiatry or general surgery within 30 days before admission for revascularization, they were classed as following outpatient care pathways. This definition was used owing to the multidisciplinary nature of foot care, and because some vascular surgeons were still coded as performing as specialists in general surgery. The earliest outpatient visit was defined as the first contact with vascular services. Patients were classed as following inpatient care pathways if they had no vascular-related outpatient visits preceding revascularization and were admitted non-electively. This included patients who  were transferred to another hospital, and/or discharged and then readmitted for revascularization. The interval between discharge and readmission was limited to 30 days.Table S3). These were collated to form seven pathways that captured the type of first contact (inpatient or outpatient), whether that contact was at a hospital with an arterial hub, and whether or not the patient was discharged from hospital before revascularization. Patients starting with an admission were grouped into three inpatient care pathways, whereas those who were initially seen at an outpatient clinic were grouped into four outpatient care pathways (Table 1). To reduce heterogeneity in the overall cohort and focus on the most common pathways in current clinical practice, a small number of patients were excluded from these seven categories: those who initially presented to an arterial hub hospital and subsequently underwent revascularization at a different arterial centre, and patients who presented to an arterial hub hospital and had a subsequent endovascular procedure at a non-arterial spoke hospital.There was a total of 19 distinct pathways starting with either an admission or outpatient visit to an arterial vascular hub or a non-arterial spoke hospital . The study adopted the POVS 201817. The severity of CLTI was categorized into two groups, depending on whether or not patients presented with tissue loss .Patient characteristics taken from the admission episode were used for analyses. Patient demographics included age on admission, sex, and region of residence. Socioeconomic deprivation was measured using the English Index of Multiple Deprivation of a patient’s residential area and converted to quintiles based on a national ranking18, which was derived using primary and secondary diagnostic codes from the index hospital admission (admission for revascularization) as well as admissions during the 12 months preceding the index admission. Acute conditions  were included in the number of co-morbidities only if they were present in a record of a hospital admission preceding the index admission. Diagnostic codes for PAD and diabetes were excluded from the RCS Charlson co-morbidity score in this study. The PAD codes formed part of the inclusion criteria for the study, whereas diabetes status was examined as a separate variable.Co-morbidities were captured using the Royal College of Surgeons (RCS) Charlson scoreU test. Cox regression was used to assess the association between time to revascularization and patient and clinical characteristics. The NHS Trusts performing revascularization were included as random effects in the multivariable Cox regression models to account for similarities in vascular services received among patients in the same Trust compared with the whole population. A half day was applied to time to revascularization in the Cox regression models where the first contact was on the same date as revascularization. A hazard ratio of less than 1 for a subgroup indicated that the time to revascularization tended to be longer for patients in that subgroup compared with patients in the reference group.Descriptive statistics were used to describe the demographic and clinical characteristics of the patient cohort. The distribution of time to revascularization for each care pathway was summarized using the median and quartiles, and presented graphically in a box plot. Differences in time to revascularization between patients following different care pathways were examined using the Mann–Whitney 20. A multivariable logistic regression model was used to assess their associations with time to revascularization, adjusting for other covariates of interest. Linear and quadratic terms of log transformation of time to revascularization were explored in the models. The NHS Trusts were included as random effects in the models to account for similarities in the postoperative outcomes among patients treated in the same organization compared with the whole population.An initial exploration of the relationship between time to revascularization and the short-term risks of postoperative mortality and major amputation during the same admission was performed visually using a symmetric nearest-neighbour smootherP < 0.050 was considered statistically significant. All analyses were done using Stata® MP version 15 .Separate regression analyses were carried out for patients following inpatient and outpatient care pathways. Owing to the possibly inaccurate clinical coding in administrative hospital data, sensitivity analyses that included additional patients with a primary diagnostic code for acute limb ischaemia and secondary diagnostic codes for CLTI were undertaken for all Cox and logistic regression analyses conducted in the main analysis. Sensitivity analyses were also conducted to explore the impact of outpatient specialties, and the time limit between the outpatient visit and the admission for revascularization. The analyses involved using a 15-day limit, a 60-day limit, and specialist in vascular surgery only. All statistical tests were two-sided and The study identified 23 274 patients aged at least 35 years who underwent lower limb procedures with an emergency admission for CLTI between April 2015 and March 2019. Of these, 17 623 (75.7 per cent) underwent revascularization as the first lower limb procedure, whereas 5651 (24.3 per cent) underwent primary amputation and were excluded. Of those undergoing revascularization, the following were excluded: 404 patients (2.3 per cent) who were on dialysis at the time of revascularization; 458 (2.6 per cent) treated at eight hospitals that had changed status from an arterial hub to a non-arterial spoke site; 142 (0.8 per cent) whose first contact for CLTI was at an arterial hub, but who subsequently underwent revascularization elsewhere; and 136 (0.8 per cent) whose time to revascularization exceeded 70 days. These exclusions left 16 483 patients for analysis.Table 2. The majority were men (65.3 per cent), and aged 70 years and over (62.3 per cent). More than half of the patients (54.8 per cent) had diabetes, and two-thirds (67.1 per cent) had at least one other Charlson co-morbidity. At the time of revascularization, 59.0 per cent of patients had tissue loss. Overall, 9470 patients (57.5 per cent) followed care pathways that started with a hospital admission, whereas 7013 (42.5 per cent) followed care pathways that started with an outpatient visit. Among those who followed an outpatient pathway, 60.4 per cent had diabetes, whereas 50.6 per cent of those who followed an inpatient pathway were diabetic. A slightly higher proportion of patients had tissue loss at the time of revascularization among those who followed an outpatient pathway than those who followed an inpatient pathway (62.4 versus 56.6 per cent respectively). The proportion of patients who followed each care pathway varied across English regions .Characteristics of patients included in the analyses are summarized in Tables 3 and 4, and Fig. 1 . Of the seven pathways, patients admitted to an arterial hub hospital as an emergency admission (pathway 1) tended to have the shortest time to revascularization, with a median of 5 (i.q.r. 2–10) days among 5560 patients. The 1783 patients admitted to a non-arterial spoke hospital (pathway 2) had a median time of 12 (7–19) days, well in excess of the target 5 days and more than twice as long as that for patients admitted to an arterial hub hospital (P < 0.001). However, the 2127 patients who were discharged after the initial emergency admission (pathway 3) experienced even longer delays to revascularization, with a median of 20 (12–30) days, and only 7.0 per cent had a procedure within 5 days.The summary of time to revascularization for each care pathway is presented in P < 0.001). As noted previously, patients who were discharged in the middle of the care pathway (pathway 7) had significantly longer delays to revascularization, with only 14.6 per cent having a procedure within 14 days. The distribution of delays for each pathway are shown in Fig. S3.For patients who followed the outpatient care pathways and were subsequently admitted to an arterial hub hospital for revascularization (3530 and 1473 patients on pathways 4 and 5 respectively), the median times to revascularization were similar, regardless of the type of hospital (hub or spoke) that patients presented to during the initial outpatient visit (median 13 (6–25) days). However, the 634 patients who were admitted to a non-arterial spoke hospital following the initial outpatient visit (pathway 6) tended to experience longer delays to revascularization (median 26 (15–35) days) than patients who followed pathways 4 and 5 (Tables 3 and 4) highlight a distinct difference between arterial hubs and spoke hospitals, regardless of how patients first attended. For the 10 563 patients  whose first admission was to an arterial hub hospital , just over half underwent revascularization within the times recommended by the Vascular Society of Great Britain and Ireland (VSGBI) . However, more than three-quarters of patients missed the time targets among the 2417  whose first admission was to a non-arterial spoke hospital (pathways 2 and 6). The proportion of patients meeting the recommended time targets was statistically significantly lower among patients following pathways 2 and 6, compared with that for patients following pathways 1, 4, and 5 .These figures for each pathway (Table S4) and the 14-day target (Table S5), notably whether or not a patient presented with tissue loss and an increasing number of co-morbidities. However, patient factors did not fully explain the differences in times to revascularization across the various types of care pathway. Figure 2 shows the adjusted hazard ratios describing the association between time to revascularization and the various inpatient and outpatient care pathways, as well as the influence of different patient and clinical characteristics. Among patients who followed the inpatient care pathways, longer delays to revascularization were associated with increasing age, patients presenting with tissue loss, and a greater number of co-morbidities . Among the patients who followed the outpatient care pathways, the associations with longer times were also statistically significant for patients presenting with tissue loss, a greater number of co-morbidities, and a diagnosis of diabetes .There were some marked differences across patient characteristics in the proportion of patients who exceeded the 5-day target (Tables 3 and 4). The univariable relationships between delays to revascularization and the risk of each postoperative outcome after revascularization across care pathways are shown in Figs S4 and S5. Generally, within the time interval containing most patients, longer delays to revascularization were associated with worse postoperative outcomes in most care pathways , after adjustment for patient and clinical characteristics. The relationship between the adjusted rate of in-hospital amputation and time to revascularization was also qualitatively different for inpatient pathways 1 and 2 compared with the others. As the delay increased, the rate of major amputation decreased slightly for pathways 1 and 2, whereas it increased for outpatient pathways and the inpatient pathway 3.Overall, 1018 patients (6.2 per cent) underwent major amputation in the postoperative phase within the same admission, whereas 864 (5.2 per cent) died in hospital after revascularization. In all, 14 733 patients (89.4 per cent) were alive and amputation-free at discharge , the change being greatest for pathway 1. The risk of in-hospital postoperative death for the outpatient pathways was also estimated to increase with longer delays, but these did not have the higher risk associated with the shortest delays . Table S6 shows the model regression coefficients for these estimates.For in-hospital death, the adjusted relationship with longer time to revascularization was also qualitatively different for the inpatient and outpatient pathways. For patients who were first admitted , the risk of postoperative death in hospital was lowest when the time to revascularization was between 3 and 7 days, and increased for both shorter and longer delays . Nonetheless, about 45 per cent of patients missed the target of a 14-day maximum delay for patients following outpatient care pathways 4 and 5. Finally, the results suggested that, after around 7 days, longer delays are associated with a slightly but statistically significantly increased risk of postoperative major amputation and in-hospital death. An additional interesting observation was the higher risk of in-hospital death among patients who were admitted as an emergency to an arterial hub (pathway 1) and fairly rapid revascularization was performed within 3 days, which could reflect the likelihood that those treated soonest were the sickest patients, often with the most considerable degree of ischaemia.This study used a novel approach to describe the complex care pathways to revascularization for patients with CLTI within the hub-and-spoke models of vascular networks in England. The results highlight a number of issues. It is of concern that patients with CLTI who were first seen at non-arterial spoke hospitals experienced longer delays to accessing revascularization procedures than those who were first seen at an arterial hub hospital. Patients admitted to a non-arterial spoke hospital (pathway 2) waited on average more than twice as long for revascularization than patients admitted to an arterial hub hospital (pathway 1). Similar differences were observed in relation to the outpatient pathways when patients were treated only at a hub or spoke (pathways 4 and 6). There were almost identical times to revascularization among patients who had an initial outpatient assessment, regardless if that was at an arterial hub or a non-arterial spoke, before subsequent admission to an arterial hub unit for revascularization  had about 1 in 10 patients waiting longer than 48 hours for transfer from a non-arterial spoke unit to an arterial hub unit14. The present study supports the survey findings, and highlighted that patients with CLTI who were transferred from a non-arterial spoke hospital to an arterial hub for revascularization (pathways 2 and 6) experienced longer delays to revascularization. An unexpected finding was the longer time to revascularization among patients presenting with tissue loss. It is possible that these patients had more severe co-morbidity or frailty, and so needed longer for investigations and preoperative optimization.The findings regarding time to revascularizsation across care pathways within the hub-and-spoke vascular networks are in agreement with those of previous studies, although few studies have investigated the relationship between delays to revascularization and postoperative outcomes in patients with CLTI. Pankhurst and Edmonds15. A Finnish study22 reported that a delay of more than 2 weeks from the primary care assessment to revascularization was an independent predictor of major amputation in patients with diabetes and CLTI presenting with tissue loss , compared with a delay of less than 2 weeks. The UK National Vascular Registry (NVR) 2020 Annual Report23 also documented higher in-hospital mortality rates in patients admitted as an emergency whose time from admission to revascularization exceeded 5 days than among those whose preoperative duration of hospital stay was 5 days or less. In the present study, postoperative outcomes were worse when associated with longer delays to revascularization, although patterns varied across care pathways. Among patients who followed the outpatient care pathways, in particular pathways 4 and 6, there were small but positive trends between time to revascularization and the adverse postoperative outcomes of major amputation and in-hospital death. For patients who were initially admitted directly to an arterial hub hospital as an emergency (pathway 1), the risk of in-hospital death was least when revascularization was performed between 3 and 7 days of admission, and then increased markedly as delays lengthened. A possible explanation is that inpatients who experienced delayed revascularization may have had a greater burden of co-morbidity requiring additional time to optimize concurrent medical co-morbidities  before revascularization was attempted. A greater proportion of high-risk patients in this group might also explain the greater risk of death among patients with the shortest times to revascularization. For the inpatients who were discharged and subsequently readmitted for revascularization (pathway 3), longer delays also appeared to be associated with an increased risk of postoperative major amputation after adjusting for other patient characteristics; however, this finding was only marginally statistically significant. Further investigations into the reasons for interim discharge and subsequent readmission for revascularization may be required to improve postoperative outcomes and reduce the amputation rates in this group of patients.There has been a long-standing concern that late presentation and delayed management of patients with CLTI could contribute to increased major lower limb amputation rates10. Centres of excellence for amputation prevention have been encouraged worldwide for managing patients with CLTI1. In 2019, the VSGBI16 introduced the PAD QIF with a 5-day target from referral to revascularization procedures for patients with CLTI who follow non-elective admission pathways, and a 14-day target for those who follow outpatient pathways. In the present study, the 5-day inpatient target was met in 50.3 per cent of patients who were admitted directly to an arterial hub hospital as an emergency, and in only 18.8 per cent of those who were admitted to a non-arterial spoke hospital preceding transfer to the regional arterial hub centre. Similar patterns were found in respect of the 14-day target among patients who followed the outpatient care pathways. There is room to improve the time to revascularization from specialist healthcare assessment for patients with CLTI in England. The Leicester Vascular Unit instituted a vascular limb salvage clinic on an outpatient basis in 2018, with the aim of meeting the 14-day target, and reported improved 12-month outcomes and reduced amputation rates for patients with CLTI compared with those managed through traditional clinical pathways24. Only 42.5 per cent of patients in this study followed outpatient care pathways, which could imply that most patients with CLTI were managed with late presentation, and a further investigation could be of importance.There is always a risk to life or limb in major arterial surgery, and vascular surgery is classified as an urgent care service in the UK25). Therefore, a combination of emergency admission, ICD-10 diagnostic codes, and OPCS-4 procedure codes was used to define the study cohort. The study was limited to emergency admissions as the NVR 2021 Annual Report26 documented that more than 95 per cent of non-elective lower limb bypass procedures performed in 2019 were due to CLTI (Fontaine score III–IV). This approach omitted patients with CLTI who had an elective revascularization, but the study was considered to capture the majority of patients with CLTI and to be representative of the whole population. Second, the cohort inclusion criteria relied on the 30-day limit and the range of outpatient specialties used to define the outpatient pathways. Sensitivity analyses that replaced the 30-day limit with 15- or 60-day limits showed that the distribution of time to revascularization for the outpatient care pathways was dependent on this limit. However, a 30-day limit was considered a reasonable interval between the outpatient visit and the admission for revascularization. Third, there is a risk of residual confounding owing to unmeasured confounding variables. This might explain the increased risk of in-hospital death for the shortest times to revascularization among patients on care pathway 1. Finally, HES only collects data on secondary care. Delays that occurred in the community between the onset of symptoms and specialist assessment by vascular services were not captured in this study.The main strength of this study is the use of both inpatient and outpatient data for all English NHS hospitals, which enabled the study to capture the complex care pathways in the real world for patients with CLTI in a comprehensive manner. This study included most patients with CLTI in England who required urgent care and underwent their first lower limb revascularization during the study interval within the hub-and-spoke model of vascular networks. This study also has several potential limitations. First, there are no explicit diagnostic codes for CLTI in the version of ICD-10 used by the HES database (in contrast to the modifications used elsewhereznac109_Supplementary_DataClick here for additional data file.


Negative Binomial Generalized Linear Mixed Models with random  and fixed (covariates) effects were performed. The results show that the number of visits to the doctor decrease significantly over time for the co-residential spousal caregivers as compared to the non-co-residential caregivers. This result highlights the fact that the Portuguese co-residential spousal caregiver group is at a higher risk of not using healthcare, thus jeopardizing their own health and continuity of care. Promoting more accessible healthcare services and implementing public policies adjusted to the needs of informal caregivers are important to improve the health and healthcare use of Portuguese spousal co-residential caregivers.Co-residential care is associated with poor caregiver health and a high burden. Although Portugal relies heavily on co-residential care by individuals aged 50 and over, studies on the impact of co-residential care provision on Portuguese caregivers’ healthcare use are lacking. This study aims to analyze the impact of co-residential care  on healthcare use of the Portuguese population aged 50 plus. Data from waves 4 ( Population ageing represents a significant challenge for long-term care systems . In EuroThe literature points out that the association between informal care provision and caregiver health is influenced by the context  in which informal care is provided, the relationship to the care recipient , and the European region ,11,12. MThe available research into the relationship between informal care provision and healthcare use by informal caregivers shows mixed results. These studies also use different measures of healthcare use assessment. A recent study  drew attThe OECD data show that Portugal is the fourth country with the highest percentage of the population aged 65 and over, with projections indicating a doubling of the population aged 80 and over between 2019 (6.4%) and 2050 (12.8%) . SeveralGiven that Portugal relies heavily on co-residential care provision by individuals aged 50 and over, our aim was to conduct the first longitudinal study analyzing the association between the provision of co-residential care and the use of healthcare among the Portuguese population aged 50 years or older. Specifically, we compared healthcare utilization by the co-residential spousal caregiver group and the non-spousal co-residential caregiver group with the non-caregiver group over time (between wave 4 and wave 6). As we focused on the middle-aged and older population—those most at risk of experiencing health problems—and informal caregivers usually provide care for long periods of time ,54, longTaking into account existing Portuguese vulnerabilities in terms of healthcare access, long-term care, and formal support to informal caregivers, as well as the vulnerabilities of the spousal caregiver group  compared with the non-caregiver group, we hypothesized that the Portuguese spousal caregiver group experiences a significant decrease in the number of visits to the doctor over time.This longitudinal study uses data from waves 4 and 6 of the SHARE  project, version 7.1.0 . SHARE is a multidisciplinary, multi-national study that includes representative samples of respondents aged 50 and over and their partners, regardless of age, from 27 European countries and Israel.http://www.share-project.org/, accessed on 1 December 2022). Portugal was part of the SHARE study in wave 4 (2011) and to the present date has conducted: wave 4 (2011); wave 6 (2015); wave 7 (2017–2018—Life Stories); COVID-19 survey wave 8 (2020); COVID-19 survey wave 9 (2021); and wave 9 (2021–2022). For more methodological details of the SHARE project, please see Börsch-Supan et al. [Since 2004, SHARE has collected data every two years, providing internationally comparable longitudinal micro-data that offer a perspective on European individuals’ public health and socio-economic living conditions  and 6 (n = 1460). With regard to Portugal, the variables of interest are only available in waves 4, 6, and 9, and the data from wave 9 are not yet available. We therefore restricted our sample to Portuguese people aged 50 and over who participated in waves 4  care  to someone living in the same household. If the answer was yes, the respondents were asked to whom they provide care. This variable was categorized into three groups: non-co-residential caregivers (if the respondent answered no to the first question); co-residential spousal caregivers (if the respondent answered yes to the first question and reported in the second question caring for the spouse living with him/her); and non-spousal co-residential caregivers (if the respondent answered yes to the first question and reported in the second question caring for other people living with him/her but not for their spouse).Based on the literature, a set of covariates were included in the model. Age at the time of the interview and gender were inserted as control variables. The employment status variable was categorized into retired and other categories . The level of education was assessed through the International Standard Classification of Education (ISCED 97), which was grouped into three levels: low education level ; medium education level ; and high education level . Financial distress was analyzed through the following question: Thinking of your household’s total monthly income, would you say that your household is able to make ends meet: 1. With great difficulty; 2. With some difficulty; 3. Fairly easily; 4. Easily. This question was assessed using a dichotomous variable, with options 1 and 2 representing the presence of financial stress (1) and options 3 and 4 representing the absence of financial stress (0).Regarding health, the number of chronic diseases and having been hospitalized in the last 12 months were also considered. We used the EURO-D scale with 12 items  to assesF) and Tukey’s post hoc tests for continuous variables and the chi-square test (X2) for categorical ones. As the SHARE sample does not have a uniform design, we used calibrated individual weights only for percentages and means. Thirdly, Generalized Linear Mixed Models for count data were applied to analyze the longitudinal association between co-residential care provision and healthcare use among the Portuguese population aged 50 and over. The Generalized Linear Mixed Models are an extension of the Generalized Linear Models, allowing correlation between observations through the insertion of random effects. The systematic component integrates fixed effects and random effects, which makes it possible to analyze data with correlated observations; that is, data repeated over time for the same individual:We first performed a descriptive analysis of all selected variables of waves 4 and 6. Since the health and economic variables had missing values greater than 5% , the impp < 0.001), Generalized Linear Mixed Models with Negative Binomial response were conducted [In this study, Generalized Linear Mixed Models with random  and fixed (covariates) effects were used. As the Generalized Linear Mixed Models with Poisson response indicated the presence of overdispersion ;−Model 1 ;−Model 2 );−Model 3 .In this sense, four Generalized Linear Mixed Models with Negative Binomial response using the maximum likelihood estimation, Laplace approximation, were analyzed:p established was 0.05.The analyses were conducted in R 4.0.2 software, library nlme, and the significance level of p  =  0.466), financial stress (p  =  0.069), number of hospitalizations in the last 12 months (p  =  0.805), physical inactivity (p  =  0.895), social activities (p  =  0.838), or doctor visits in the last 12 months (p  =  0.154).Model 3 further shows that having a higher educational level  was associated with a 24% increase in the number of visits to the doctor. Along the same lines, individuals who reported having been hospitalized in the last 12 months , those who reported four or more depressive symptoms , and those who were physically inactive  were associated with an increase of 72%, 26%, and 16%, respectively, in the number of visits to the doctor. Furthermore, each additional chronic disease reported is associated with 14%  more visits to the doctor. Lastly, each additional time (wave) is associated with an increase of 8%  in the number of visits to the doctor. The interaction term between providing co-residential care and gender was also tested  as compared to non-co-residential caregivers. Our findings do not support the results cited by Zwart et al. , which sTo our knowledge, this is the first study analyzing the longitudinal association between providing co-residential care and healthcare usage in the Portuguese population aged 50 plus. This study aims to contribute to the literature by focusing on co-residential care provision in Portugal and by differentiating between two groups of co-residential care providers: spousal caregivers and non-spousal caregivers. Nevertheless, this study has limitations. The dependent variable number of visits to the doctor in the last 12 months is based on memory and may be subject to underreporting (memory bias). Furthermore, this question underwent some changes between waves, which may have affected the analysis . Because Portugal only joined the SHARE study at wave 4 and our variables of interest are only available for waves 4 and 6, our analysis only covered two waves. In addition, the SHARE study does not indicate the number of hours of informal care provided by the informal caregivers, which prevented us from analyzing the intensity of care provided by informal caregivers.Given the different levels of development of social and health systems and different intensities of informal care provision in European countries, further research into healthcare use among informal caregivers should adopt a country perspective. It should also consider the place where the care is provided and the type of caregiver/care recipients relationship. The long-term impacts of informal caregiving on caregiver healthcare use, including after the death of the person cared for, can also help us better understand the real impact of informal caregiving on caregiver health and on healthcare use.Our study showed that between wave 4 (2011) and wave 6 (2015), compared to the non-caregiver group, the Portuguese co-residential spouse caregiver group showed a statistically significant decrease in the number of visits to the doctor. The decrease may indicate that these co-residential spouse caregivers are not able to meet their health needs, thus jeopardizing their health and continuity of care. As access to healthcare is a prerequisite for the fundamental right of health , it is cTo achieve this, we recommend increased economic investment in long-term care services, as well as the implementation of social and health public policies adjusted to the needs and types of informal caregivers. Since informal care in Portugal is associated with a social and family duty and a large proportion of informal caregivers do not regard themselves as such, health and social professionals should provide them with advice about their status, their rights, and the support to which they may be entitled. Formal status for Portuguese informal caregivers should also include an assessment of informal caregivers’ needs. This should lead to the provision of psychosocial support and medical support  for co-residential spouse caregivers. Lastly, to ensure that co-residential spouse caregivers have time to rest and to promote their health, the Portuguese government should establish more effective informal caregiver respite care policies. Overall, there is a need to promote more accessible healthcare services and to implement public social and health policies that are tailored to the needs of informal caregivers in order to improve the health and healthcare use of Portuguese co-residential spousal caregivers.