Highly polymorphic interaction of KIR3DL1 and KIR3DS1 with HLA class I ligands modulates the effector functions of natural killer (NK) cells and some T cells. This genetically determined diversity ...affects severity of infections, immune-mediated diseases, and some cancers, and impacts the course of immunotherapies, including transplantation. KIR3DL1 is an inhibitory receptor, and KIR3DS1 is an activating receptor encoded by the KIR3DL1/S1 gene that has more than 200 diverse and divergent alleles. Determination of KIR3DL1/S1 genotypes for medical application is hampered by complex sequence and structural variation, requiring targeted approaches to generate and analyze high-resolution allele data. To overcome these obstacles, we developed and optimized a model for imputing KIR3DL1/S1 alleles at high-resolution from whole-genome SNP data. We designed the model to represent a substantial component of human genetic diversity. Our Global imputation model is effective at genotyping KIR3DL1/S1 alleles with an accuracy ranging from 88% in Africans to 97% in East Asians, with mean specificity of 99% and sensitivity of 95% for alleles >1% frequency. We used the established algorithm of the HIBAG program, in a modification named Pulling Out Natural killer cell Genomics (PONG). Because HIBAG was designed to impute HLA alleles also from whole-genome SNP data, PONG allows combinatorial diversity of KIR3DL1/S1 with HLA-A and -B to be analyzed using complementary techniques on a single data source. The use of PONG thus negates the need for targeted sequencing data in very large-scale association studies where such methods might not be tractable.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractBackgroundAcute Coronary Syndrome (ACS) is currently diagnosed using a 12‑lead Electrocardiogram (ECG). Our recent work however has shown that interpretation of the 12‑lead ECG is complex and ...that clinicians can be sub-optimal in their interpretation. Additionally, ECG does not always identify acute total occlusions in certain patients. PurposeThe aim of the present study was to undertake an exploratory analysis to compare protein expression profiles of ACS patients that may in the future augment ECG diagnosis. MethodsPatients were recruited consecutively at the cardiac catheterization laboratory at Altnagelvin Hospital over a period of 6 months. A low risk control group was recruited by advertisement. Blood samples were analysed using the multiplex proximity extension assays by OLINK proteomics. Support vector machine (SVM) learning was used as a classifier to distinguish between patient groups on training data. The ST segment elevation level was extracted from each ECG for a subset of patients and combined with the protein markers. Quadratic SVM (QSVM) learning was then used as a classifier to distinguish STEMI from NSTEMI on training and test data. ResultsOf the 344 participants recruited, 77 were initially diagnosed with NSTEMI, 7 with STEMI, and 81 were low risk controls. The other participants were those diagnosed with angina (stable and unstable) or non-cardiac patients. Of the 368 proteins analysed, 20 proteins together could significantly differentiate between patients with ACS and patients with stable angina (ROC-AUC = 0.96). Six proteins discriminated significantly between the stable angina and the low risk control groups (ROC-AUC = 1.0). Additionally, 16 proteins together perfectly discriminated between the STEMI and NSTEMI patients (ROC-AUC = 1). ECG comparisons with the protein biomarker data for a subset of patients (STEMI n = 6 and NSTEMI n = 6), demonstrated that 21 features (20 proteins + ST elevation) resulted in the highest classification accuracy 91.7% (ROC-AUC = 0.94). The 20 proteins without the ST elevation feature gave an accuracy of 80.6% (ROC-AUC 0.91), while the ST elevation feature without the protein biomarkers resulted in an accuracy of 69.3% (ROC-AUC = 0.81). ConclusionsThis preliminary study identifies panels of proteins that should be further explored in prospective studies as potential biomarkers that may augment ECG diagnosis and stratification of ACS. This work also highlights the importance for future studies to be designed to allow a comparison of blood biomarkers not only with ECG's but also with cardio angiograms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND:Prisoners are disproportionately affected by cardiovascular disease and its risk factors. However, primary prevention of cardiovascular disease in correctional settings has been widely ...neglected, and there is little information on interventions to improve the cardiovascular health of prisoners while incarcerated.
OBJECTIVE:The aim of this study was to systematically review published literature to identify interventions to improve the health factors or behaviors of the cardiovascular health of prisoners during incarceration.
METHODS:Selected databases were searched using terms related to prisoners and cardiovascular disease. Studies were included if they had prisoners as participants and measured outcomes of cardiovascular health. Narrative synthesis was used to organize the evidence from the studies.
RESULTS:Twelve articles detailing 11 studies were identified. Most of the studies involved only men. Interventions were classified into 4 typesstructured physical activity, nutrition, mixed with physical activity and educational sessions, and smoking cessation. Most studies measured short-term outcomes relating to cardiovascular health such as changes in blood pressure and weight. Only 4 studies were of high quality. Structured physical activity interventions, nutrition interventions, and smoking cessation interventions delivered in a group setting had significant effects on at least 1 measured outcome. The effect of mixed interventions could not be determined.
CONCLUSIONS:Structured physical activity interventions, nutrition interventions, and smoking cessation interventions delivered in a group setting can improve health factors or behaviors of the cardiovascular health of prisoners during incarceration. More high-quality research is needed to increase the evidence base on the effectiveness of these interventions in the correctional setting.
Objectives(1) Assess whether cardiac rehabilitation (CR) is a feasible and acceptable model of rehabilitation for postsurgical colorectal cancer (CRC) survivors, (2) evaluate trial procedures. This ...article reports the results of the first objective.Design and settingA pragmatic pilot randomised controlled trial with embedded qualitative study was conducted in 3 UK hospitals with CR facilities. Descriptive statistics were used to summarise trial parameters indicative of intervention feasibility and acceptability. Interviews and focus groups were conducted and data analysed thematically.ParticipantsPeople with CRC were considered for inclusion in the trial if they were ≥18 years old, diagnosed with primary CRC and in the recovery period postsurgery (they could still be receiving adjuvant therapy). 31% (n=41) of all eligible CRC survivors consented to participate in the trial. 22 of these CRC survivors, and 8 people with cardiovascular disease (CVD), 5 CRC nurses and 6 CR clinicians participated in the qualitative study.InterventionReferral of postsurgical CRC survivors to weekly CR exercise classes and information sessions. Classes included CRC survivors and people with CVD. CR nurses and physiotherapists were given training about cancer and exercise.ResultsBarriers to CR were protracted recoveries from surgery, ongoing treatments and poor mobility. No adverse events were reported during the trial, suggesting that CR is safe. 62% of participants completed the intervention as per protocol and had high levels of attendance. 20 health professionals attended the cancer and exercise training course, rating it as excellent. Participants perceived that CR increased CRC survivors’ confidence and motivation to exercise, and offered peer support. CR professionals were concerned about CR capacity to accommodate cancer survivors and their ability to provide psychosocial support to this group of patients.ConclusionsCR is feasible and acceptable for postsurgical CRC survivors. A large-scale effectiveness trial of the intervention should be conducted.Trial registration numberISRCTN63510637.
Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery, as this is safer than the femoral approach. However, ...despite improvements in technology and techniques, complications can occur. The most common complication, arterial spasm, can cause intense pain and, in some cases, procedural failure. The incidence of spasm is dependent on several variables, including operator experience, artery size, and equipment used. An anti-spasmolytic cocktail can be applied to reduce spasm, which usually includes an exogenous nitric oxide (NO) donor (glyceryl trinitrate). NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention. However, systemic administration can result in unwanted side-effects, such as hypotension. A method that adopts local delivery of NO might be advantageous. This review article describes the mechanisms involved in radial artery spasm, discusses the advantages and disadvantages of current strategies to reduce spasm, and highlight the potential of NO-loaded nanoporous materials for use in this setting.
Background
An acute cardiac incident is a life-changing event that often necessitates surgery. Although surgery has high success rates, rehabilitation, behavioral changes, and self-care are critical ...to long-term health. Recent systematic reviews have highlighted the potential of technology in this area; however, significant shortcomings have also been identified, particularly with regard to patient experience.
Objective
This study aims to improve future systems and to explore the experiences of cardiac patients during key phases after hospitalization: recuperation, initial rehabilitation, and long-term self-management. The key objective is to provide a holistic understanding of behavioral factors that impact people across these phases, understand how experiences evolve over time, and provide user-centered recommendations to improve the design of cardiac rehabilitation and self-management technologies.
Methods
Semistructured interviews were conducted with people who attended rehabilitation programs following hospitalization for acute cardiac events. Interviews were developed and data were analyzed via the Theoretical Domains Framework, a pragmatic framework that synthesizes prior theories of behavioral change.
Results
Three phases that arise posthospitalization were examined, namely, recuperation, rehabilitation, and long-term self-management. Through these phases, we describe the impact of key factors and important changes that occur in patients’ experiences over time, including the desire for and redefinition of normal life, the need for different types of formal and informal knowledge, the benefits of safe zoning and connectedness, and the need to recognize capability. The use of the Theoretical Domains Framework allows us to show how factors that influence behavior evolve over time and to identify potential sources of tension.
Conclusions
This study provides empirically grounded recommendations for the design of technology-mediated cardiac rehabilitation and self-management systems. Key recommendations include the use of technology to support a normal life, leveraging social influences to extend participants’ sense of normality, the use of technology to provide a safe zone, the need to support both emotional and physical well-being, and a focus on recognizing capability and providing recommendations that are positive and reinforce this capability.
There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF).
...The objective was to describe prescribers' experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations.
A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes.
One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents' descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances.
While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Introduction: Primary percutaneous coronary intervention (PPCI) establishes flow in an obstructed coronary artery. Before this, the electrocardiogram (ECG) is used to signpost patients to PPCI. We ...evaluate the factors that may have influenced the decision pathway. Methods: Case reports from patients referred for PPCI were evaluated as part of a compulsory audit. Demographics, symptoms, computer ECG interpretation, activator interpretation, time of referral, 30 day and 12 month mortalities were recorded. Computer and activator interpretations were simplified to being suggestive of acute myocardial infarction (MI). Results: 942 patients (68% male), mean age 68 + 17 years referred for PPCI were appropriately turned down for catheterisation. 62% (584) of these referrals were 'out of hours', with less referrals made on Saturdays and Sundays. Peak referral times occurred at 11am (75/9418%), 3pm (57/941 6%) and 8pm (63/941 7%). 12 month mortality rates were highest if patients were referred at 3am (7/22 32%). 76 (8.1%) patients died within 30 days and 108 (11.5%) within 12 months. 373 (39.6%) had chest pain, 142 (15.1%) had resolved chest pain leaving 427 (45.4%) who did not experience chest pain. 394 (42%) computerised diagnoses were suggestive of acute MI whereas 327 (35%) activator diagnoses were suggestive of acute MI. There were 182 (19%) cases where the human and computer agreed that there was an acute MI. They agreed more often when there was not an acute MI (403 43% of cases). Overall agreement rate was 62%. There were 145 (15.4%) cases where the computer did not suggest an acute MI but the activator did. There were 212 (22.5%) cases where the computer suggested acute MI but the activator did not. Age (p<0.001), a computerised acute MI diagnosis and being an out of hour referral increased the odds of mortality after one year (Table 1). Activator and computer acute MI agreement and having chest pain (p<0.01) reduced the odds of mortality after one year. The odds of mortality within 12 months of referral was lower in patients with chest pain compared to those patients without chest pain. Conclusion: Mortality in patients appropriately turned down for PPCI is higher than the reported mortality for STEMI patients at 12 months. Agreement between computerised and human interpretation is poor perhaps leading to a high inappropriate referral rate. Work is needed to improve machine and human decision making to ensure that patients are signposted to the correct treatment facility for time critical therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment.
The purpose of this study was to investigate cardiovascular mortality and medication use after ...takotsubo syndrome.
In a case-control study, all patients with takotsubo syndrome in Scotland between 2010 and 2017 (n = 620) were age, sex, and geographically matched to individuals in the general population (1:4, n = 2,480) and contemporaneous patients with acute myocardial infarction (1:1, n = 620). Electronic health record data linkage of mortality outcomes and drug prescribing were analyzed using Cox proportional hazard regression models.
Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow-up. This exceeded mortality rates in the general population (N = 374 15%; HR: 1.78 95% CI: 1.48-2.15,
< 0.0001), especially for cardiovascular (HR: 2.47 95% CI: 1.81-3.39,
< 0.001) but also noncardiovascular (HR: 1.48 95% CI: 1.16-1.87,
= 0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR: 0.76 95% CI: 0.62-0.94,
= 0.012), which was attributable to lower rates of cardiovascular (HR: 0.61 95% CI: 0.44-0.84,
= 0.002) but not non-cardiovascular (HR: 0.92 95% CI: 0.69-1.23,
= 0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (
= 0.01), anti-inflammatory (
= 0.002), and psychotropic (
< 0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome.
In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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