Publications

Long COVID (LC) affects approximately 45% of COVID-19 survivors,1 featuring persistent symptoms lasting over 4 weeks without an alternative explanation.2 The recent development of LC services aims to provide structured or integrated care.3 Given the current challenges in the UK healthcare system, we explored access to care for people with LC. We compared this to other long-term conditions (LTCs), concerning four filters for accessing care as defined in the Pathways-to-Care model,4 to inform policy and service planning across diseases and specialities. Those filters include the person's decision to seek care (filter 1), the decision of the General Practitioner (GP) to provide diagnosis and treatment in primary care (filter 2), the GP's decision to refer the patient to specialist care (filter 3), and the arrival of the patient in outpatient specialist care (filter 4). The second filter concerns a complex process combining the patient's perspective of their health problems being recognized by the GP and diagnostic, treatment, or referral actions taken by GPs that indicate that the GP recognized the patient's problem. We expanded this recognition concept to include other healthcare professionals (HCPs) in primary care. We conducted an online survey from April to June 2022 as part of the STIMULATE-ICP-Delphi study. Using snowball sampling, we recruited 283 participants, including patients and HCPs, with experience in LC and LTCs. We incorporated patient and public involvement and used descriptive statistics. The protocol for this Delphi study was approved by the University of York Department of Health Sciences Research Governance Committee in 2021 (HSRGC/2021/ 478/A: STIMULATE-ICP) and has been published.5 The process of seeking treatment, treatment(s) offered, and referring for specialist support was explored among patients, GPs, and other HCPs. Respondents' age, sex, relationship and employment status, ethnicity, and locations were collected. The survey included questions about the relevant disease experience as a patient or HCP. For filters 2, 3, and 4, patients were asked to indicate if they received any care and to specify the care offered (e.g., tests) using drop-down and free-response formats. Regarding filter 2—recognition by the HCP—this was operationalized as whether patients were offered diagnostic tests or treatment in primary care or referred by the GP to specialist care. Patients were also asked to provide their perspectives on their health problems being recognized by their HCP. Similar questions were asked of HCPs for filters 2, 3, and 4. Table S1 provides demographic information for 283 participants. Figure S1 outlines participant screening, and Figure S2 displays responses and missing data. Ninety-six percent of patients with LC and 98% with LTCs sought health care (filter 1). The most common symptom leading to care-seeking for both groups was tiredness (for the full list, Table S2). LC patients had varying symptom durations, while most LTCs patients had symptoms lasting over 18 months (Table S2). All patients with LC and with LTCs visiting their GP were provided access to care: diagnostic tests or treatment in primary care or referral to specialist services (filter 2). The proportion of LC and LTC patients who received diagnostic tests (mostly blood tests) and treatments was similar. For LC, 71% of HCPs indicated they provided diagnostic tests and 57% treatment in their practice. For LTCs, this was reported as 80% and 90%, respectively. Although all patients received access to primary care, only 51% of LC patients and 62% with LTCs reported that their HCPs recognized their problem when explicitly asked. GPs referred 71% (LC patients) and 76% (LTC patients) to specialists. Of those with LC, 65 (35%) received referrals to post-COVID clinics, while others were referred to clinics relevant to their dominant symptoms, such as cardiology, neurology, or respiratory clinics. More than one referral was made for 46% of LC patients and 28% of LTC patients. All GPs reported referring patients with LC to a specialist, and all reported that they referred patients with LTCs for specialist care (filter 3). Two-thirds of referred patients attended specialist appointments, while around one-third in each group were on a waiting list (filter 4). Figure 1 presents a revised model, reflecting the proportion of participants who progressed from seeking health care to accessing specialist care. The original pathway-to-care model for mental health care described by Goldberg and Huxley has a pyramidal shape. However, the model emanating from our study, as reported by patients and HCPs, looks more block-shaped. Patients with LC and LTCs share similar experiences navigating the four filters to access care. Almost all patients with symptoms seek care, and all of those are provided access to primary care by the GP through diagnosis and treatment. This access level is 100%, whereas, in Goldberg and Huxley's findings, only 61% of patients passed filter 2 for mental health care. This might be explained by a difference in access to mental health services versus access to somatic health services. Another factor could be improved access to primary care since the 1980s. Primary care, led by GPs, has evolved to manage complex and multimorbid patients, with expanded support from practice nurses and allied health professionals. A Kings Fund report showed that the productivity of the NHS in terms of service provision has increased massively, and the majority of NHS activity is in primary care.6 Also, LC clinics have been set up to address the new demands during the pandemic. Referral rates to specialists were also high; however, in both groups, access to specialists for those referred needed to be completed. This might be caused by delays due to waiting lists, as the number of people deciding not to access specialist care was low. The percentage of people on a waiting list was alarming and this was a problem that had been highlighted by the King's Fund for elective hospital treatments. This study showed it also applied to outpatient specialist access to care and might need a similar, concerted, vigorous approach as suggested by the King's Fund.7 Most patients referred to specialists would be seen, assessed, and treatment recommendations made before being discharged to primary care. Specialists would only hold onto patients if further investigations were planned or if treatment required ongoing secondary care input. The study highlighted the need for enhanced data exchange between primary and secondary care via a shared electronic health record. Such improvements support ongoing monitoring, case identification, and resource allocation decisions. The concept of the “learning health system,” with data flowing between routine care, science, and evidence, was crucial8 to avoid difficulties moving forward and to prevent worsening inequalities. Alternative care models, such as the Nuka model in Alaska, could be explored to improve access to specialist knowledge in primary care. The Nuka System of Care uses secondary care expertise to inform primary care practice, with multidisciplinary teams providing integrated health and care services in primary care centers and the community, coordinating with other services.9 Other alternative models relevant to integrating primary and secondary care, especially for comorbid somatic and psychiatric LTCs, could be psychiatric consultation models in primary care. These were effective in comorbid depression and long-term somatic conditions, especially if embedded in collaborative care10 and if after the consultation, a consultation letter was provided by the psychiatry consultant to the primary care team, to facilitate discussion with the patient about their future treatment. The discrepancy between patients' perceived recognition of the problem and the high level of actions taken by HCPs was striking. In both patient' groups, having access did not necessarily mean that the HCP recognized their problem. For LC, this discrepancy might be explained by the fact that it was a new condition for which much was still unknown, or by the limited time for engagement between patients and their GPs. In other LTCs, this might be due to the delegation of treatment to practice nurses, resulting in less contact with GPs, as was typical for diabetes, or cardiovascular conditions. This study was the first to explore barriers and facilitators to care access for people with LC and with other LTCs using the pathway-to-care filter model. The large and diverse sample provided the perspectives of patients and clinicians for all relevant filters. The finding that patient responses were similar to those of HCPs suggested that this survey gave a balanced perspective on pathways to care for LC and LTCs. Self-reporting in this context could be considered as equivalent to a confirmed medical diagnosis, and the classification of LC or a LTC was probably correct in this sample.11 Nevertheless, there might be bias in the classification of the main symptom. For example, breathlessness could be classified as cardiological but also as respiratory. Future research could examine the factors that impede or promote access to care for patients with LC and other LTCs such as health inequalities and demographic characteristics. The extent to which primary care provided a holding relationship12 for patients with LC and LTCs still needs to be explored, especially the interaction between primary care, specialist care, and A&E services. Research could help shape the reorganization of primary care services integrated with secondary care. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Whole body exercise provides protection against endothelial ischemia-reperfusion (IR) injury. In this crossover study, we examined the effects of <i>1</i>) single bout of local exercise (handgrip, squats) on endothelial responses to IR, and <i>2</i>) if 7 days of daily local exercise bolsters these effects in individuals with cardiovascular disease (CVD) risk factors. Fifteen participants (9 women, 58 ± 5 yr, ≥2 CVD risk factors) attended the laboratory for six visits. Subsequent to familiarization (<i>visit 1</i>), during <i>visit 2</i> (control) brachial artery flow-mediated dilation (FMD) was measured before and after IR (15-min upper-arm ischemia, 15-min reperfusion). One week later, participants were randomized to 4 × 5-min unilateral handgrip (50% maximal voluntary contraction, 25 rpm) or squat exercises (15 rpm), followed by IR plus FMD measurements. Subsequently, home-based exercise was performed (6 days), followed by another visit to the laboratory for the IR protocol plus FMD measurements (18-24 h after the last exercise bout). After a 2-wk washout period, procedures were repeated with the alternative exercise mode. For a single exercise bout, we found a significant IR injury × exercise mode interaction (<i>P</i> < 0.01) but no main effect of injury (<i>P</i> = 0.08) or condition (<i>P</i> = 0.61). A lower post-IR FMD was evident after control (pre-IR: 4.3 ± 2.1% to post-IR: 2.9 ± 1.9%, <i>P</i> < 0.01) but not after handgrip (pre-IR: 3.8 ± 1.6% to post-IR: 3.4 ± 1.5%, <i>P</i> = 0.31) or squats (pre-IR: 3.9 ± 1.8% to post-IR: 4.0 ± 1.9%, <i>P</i> = 0.74). After 7 days of daily exercise, we found no change in FMD post-IR following handgrip (pre-IR: 4.3 ± 1.9% to post-IR: 4.7 ± 3.2%) or squats (pre-IR: 3.7 ± 2.1% to post-IR: 4.7 ± 3.0%, <i>P</i> > 0.05). Single bouts of dynamic, local exercise (handgrip, squats) provide remote protection against endothelial IR-induced injury in individuals with CVD risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.<b>NEW & NOTEWORTHY</b> We show that single bouts of dynamic handgrip and squat exercise provide remote protection against endothelial ischemia-reperfusion (IR)-induced injury in individuals with cardiovascular disease (CVD) risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.

The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner.

<sec> <title>BACKGROUND</title> Chronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. </sec> <sec> <title>OBJECTIVE</title> This study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. </sec> <sec> <title>METHODS</title> The analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (&amp;lt;75 nmol/L) and high (≥75 nmol/L). To assess participants’ baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures. </sec> <sec> <title>RESULTS</title> A total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did not achieve statistical significance among all participants, with a hazard ratio (HR) of 1.05 and a 95% CI ranging from 0.98 to 1.13 (&lt;i&gt;P&lt;/i&gt;=.16). However, a notable interaction was identified between Lp(a) and UACR in relation to CKD risk (&lt;i&gt;P&lt;/i&gt; for interaction=.04), whereas no significant interaction was observed between Lp(a) and eGFR (&lt;i&gt;P&lt;/i&gt; for interaction=.96). When compared with the reference group with low Lp(a) and low-normal UACR (&amp;lt;10 mg/g), the group with high Lp(a) and low-normal UACR exhibited a nonsignificant association with CKD risk (HR 0.98, 95% CI 0.90-1.08; &lt;i&gt;P&lt;/i&gt;=.74). By contrast, both the low Lp(a) and high-normal UACR (≥10 mg/g) group (HR 1.16, 95% CI 1.08-1.24; &lt;i&gt;P&lt;/i&gt;&amp;lt;.001) and the high Lp(a) and high-normal UACR group (HR 1.32, 95% CI 1.19-1.46; &lt;i&gt;P&lt;/i&gt;&amp;lt;.001) demonstrated significant associations with increased CKD risks. In individuals with high-normal UACR, elevated Lp(a) was linked to a significant increase in CKD risk, with an HR of 1.14 and a 95% CI ranging from 1.03 to 1.26 (&lt;i&gt;P&lt;/i&gt;=.01). Subgroup analyses and sensitivity analyses consistently produced results that were largely in line with the main findings. </sec> <sec> <title>CONCLUSIONS</title> The analysis revealed a significant interaction between Lp(a) and UACR in relation to CKD risk. This implies that Lp(a) may act as a risk factor for CKD even when considering UACR. Our findings have the potential to provide valuable insights into the assessment and prevention of CKD, emphasizing the combined impact of Lp(a) and UACR from a public health perspective within the general population. This could contribute to enhancing public awareness regarding the management of Lp(a) for the prevention of CKD. </sec>

Despite the huge progress made in the both understanding the mechanisms and the management of atrial fibrillation (AF) this arrhythmia still represents an important health and social burden. Atrial fibrillation is increasing in frequency and is a major cause of death, stroke, heart failure, cognitive decline, and hospitalizations. New data have emerged emphasizing the multidisciplinary approach to better management of this common arrhythmia. Despite the availability of AF management guidelines, practice among European centres may differ from the current guideline recommendations. The scope of the current European Heart Rhythm Association (EHRA) survey is to evaluate the extent of the disparities between clinical practice and the 2016 AF European Society of Cardiology (ESC) guidelines. Our survey examined important topics such as screening for AF, initial therapy, rhythm strategy, and stroke and bleeding risk assessment. In general, there was a high adherence to the new ESC AF guidelines among European cardiologists.

A new diagnosis of retinal vascular occlusion in patients without prior AF was associated with increased risk of incident AF, particularly amongst patients with RAO. Awareness of AF in patients with retinal vascular occlusions is advised.

Approximately half of the AF patients received optimal ATT according to guideline recommendations, which was associated with a lower risk of stroke. Furthermore, there was no interaction for the 2 populations and the influence of ATT adherence.

Abstract Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOAC). However, it comes with an increased risk of bleeding and therefore, counselling patients on their individual risk is important. Although majority of patients initiated on DOAC have been represented within the clinical trials, there are some cohorts which are under-represented in whom clinicians are unable to practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, 5 recent open-label industry sponsored AF trials were compared with Real-World data (RWD) was sourced from the HealthVerity Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs 65.3 ±10.7 years old, p&amp;lt;0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs 2.87 ± 1.73, p&amp;lt;0.001) and HAD-BLED scores (2.13 ± 1.02 vs 1/04 ± 0.93, p&amp;lt;0.001) when compared to the trial data. When comparing the incidence of first major bleed at 12 months post treatment initiation, rates in the RWD cohort was significantly higher (10.69 vs 18.97 per 100 person-years). The impact of comorbidities such as age, CHA2DS2VASc and HAD-BLED scores were similar in both cohorts, however, there was an under-representation of older, females and more co-morbid patients within the clinical trial cohort. Conclusion DOAC treated patients have higher bleeding incidence rate in the RWD cohort as compared to clinical trials. This can be explained by the older patient age group with more complex medical histories and higher HAS-BLED scores. The under-representation of higher risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real world clinical practice.

Abstract Background Patients with atrial fibrillation and valvular heart disease (VHD) beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have been associated with a higher risk of thromboembolism compared with patients with atrial fibrillation and no VHD. A minor but important proportion of patients with atrial fibrillation and EHRA Type 2 VHD has 0 or 1 coexisting CHA2DS2-VASc stroke risk factors, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are “truly low” risk of stroke has not been investigated. We aimed to describe the risk of thromboembolism in non-anticoagulated atrial fibrillation patients with and without EHRA Type 2 VHD and with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score. Methods Cohort study of atrial fibrillation patients with and without EHRA Type 2 VHD identified in nationwide Danish registries from 2000–2018. 1-year risk of thromboembolism was estimated for the study population divided into four subgroups in relation to non-sex CHA2DS2-VASc score comorbidities (except for previous thromboembolism) and age category (&amp;lt;65 or 65–74 years). Results We identified 1,907 and 53,707 incident atrial fibrillation patients with and without EHRA Type 2 VHD. Median age was 57 years and 55 years in patients with and without EHRA Type 2 VHD and 0 comorbidities and 67 years in patients with and without EHRA Type 2 VHD and 1 comorbidity. Percentage of females was approximately 44% in patients with and without EHRA Type 2 VHD and 0 comorbidities and 33% and 36% in patients with and without EHRA Type 2 VHD and 1 comorbidity. In patients with 1 comorbidity, the most prevalent stroke risk factor of the CHA2DS2-VASc score was hypertension. Cumulative incidence of thromboembolism according to presence of EHRA Type 2 VHD and age category in patients with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score are presented in the figure (the curve for patients with EHRA Type 2 VHD aged 65–74 years and with 0 comorbidities was omitted due to few events). At 1 year after atrial fibrillation diagnosis, patients with and without EHRA Type 2 VHD aged &amp;lt;65 or 65–74 years and with 0 or 1 comorbidity of the CHA2DS2-VASc score had a risk of thromboembolism ranging 1.3–2.2% and 0.5–1.7% according to age category and number of comorbidities of the CHA2DS2-VASc score. In patients with EHRA Type 2 VHD aged &amp;lt;65 years with 0 or 1 comorbidity, the risk was 1.5% and 2.2% at 1 year after the diagnosis of atrial fibrillation. Conclusion In atrial fibrillation patients with EHRA Type 2 VHD, we observed a risk of thromboembolism that may exceed the level above which oral anticoagulation is considered beneficial. No trial has specifically examined patients with EHRA Type 2 VHD and low CHA2DS2-VASc scores and, therefore, our observations may be important to patients who are not recommended oral anticoagulant therapy according to contemporary guidelines. Figure 1. Cumulative incidence of thromboembolism Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The study was supported by “The BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA) 2018” and the Obel Family Foundation.

The use of DOAC in AF significantly reduces dementia risk compared with warfarin, particularly in Asian patients. The possible reversal of this effect with increasing age merits further randomized trials with long-term follow-up. (Dementia Risk of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation: A Systematic Review and Meta-Analysis; CRD42022365634).

CR was associated with significantly lower 12-month MACE in patients with simple ConHD with concomitant HF compared to usual care.

Atrial fibrillation -Stroke prevention -General 611ponents among non-valvular atrial fibrillation (NVAF) patients prescribed NOACs or warfarin, stratified by index NOAC dosage.Methods: A retrospective observational study of NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from 01JAN2013-30SEP2015 was conducted using CMS Medicare data and four other US commercial claims databases, covering >180 million beneficiaries annually (∼56% of US population).After propensity score matching in each database between each standard NOAC dose and warfarin (5mg BID apixaban-warfarin, 150mg BID dabigatranwarfarin, and 20mg QD rivaroxaban-warfarin), as well as each lower NOAC dose and warfarin (2.5mg BID apixaban-warfarin, 75mg BID dabigatran-warfarin, and 10 or 15mg QD rivaroxaban-warfarin), the resulting patient records were pooled.Cox models were used to estimate S/SE and MB hazard ratios (identified by inpatient claims).S/SE included ischemic stroke, hemorrhagic stroke, and SE; MB included gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), and other MB.Results: Patients initiating lower and standard NOAC doses had different baseline characteristics, such as age and renal disease.Patient data were assessed for a mean of 7-8 months.Standard-and lower-dose apixaban patients were each associated with lower rates of S/SE and MB versus warfarin.Standardand lower-dose dabigatran patients each had similar rates of S/SE compared to warfarin.Standard-dose dabigatran patients had a lower rate of MB and lowerdose dabigatran patients had a similar rate of MB versus warfarin.Standard-dose rivaroxaban patients were associated with a lower S/SE rate, and lower-dose rivaroxaban patients had a similar rate of S/SE compared to warfarin.Standardand lower-dose rivaroxaban patients were each associated with higher MB rates compared to warfarin.All doses of NOACs were associated with lower rates of ICH compared to warfarin.The hazard ratios for the S/SE, MB, and their components are shown in the figure .Conclusions: In this large observational study, apixaban was the only NOAC associated with lower rates of S/SE and MB for both doses compared to warfarin.Dose selection criteria cannot be ascertained from current data sources.Future studies of patients who were appropriately dosed should be warranted.