Determining patient value profiles in psoriasis.

BACKGROUND: Healthcare professionals (HCPs) should strive to create the maximum value for their patients in which value is defined as the patient-relevant health outcomes achieved per costs made. However, currently it remains difficult to determine which outcomes matter to an individual psoriasis patient. OBJECTIVE: To define outcome profiles, or so called 'patient value profiles', within a cohort of psoriasis patients that can be translated to daily practice to increase value for the individual patient. METHODS: Hierarchical clustering on principal components (HCPC) was used to identify groups of patients sharing the same profile within an outcome ranking exercise. Once the clusters were defined, their characterization was provided based on a V-test. In a final step, a multi-class decision tree (MDT) based on relevant socio-demographic and clinical variables was built to allocate patients to a cluster. RESULTS: In the ranking exercise 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2) and median duration of psoriasis was 17.0 (IQR 20.0) years. Primary treatment varied from topicals to biologicals. We found three distinct patient value profiles in this cohort (QoL, cost and treatment). A MDT was built which had an accuracy of 64%. CONCLUSION: We found three distinct patient value profiles in a cohort of psoriasis patients and patients can be easily assigned to one of these profiles based on a MDT. HCPs can use these profiles to steer psoriasis management accordingly allowing for a more goal-orientated approach.

Practical recommendations for systemic treatment in psoriasis in case of coexisting inflammatory, neurologic, infectious or malignant disorders (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis; part 2).

BACKGROUND: Psoriasis patients carry an increased risk for associated comorbidities. Dermatologists have to be aware of the effects of systemic treatments not only on psoriasis but also on co-occurring diseases. In case of other coexisting inflammatory diseases, the right psoriasis treatment may improve both disorders. For infectious and malignant disorders, some treatments have to be avoided as they may be harmful. OBJECTIVE: The primary objective of this project was to collect evidence for the creation of practice guidelines for systemic treatment of psoriasis (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis). METHODS: Evidence-based recommendations were formulated using a quasi-Delphi methodology after a systematic search of the literature and a consensus procedure involving eight psoriasis experts. RESULTS: Recommendations are given on the use of systemic treatment in psoriatic arthritis, inflammatory bowel disease, demyelinating disorders, hepatitis B and C, HIV and cancer. CONCLUSION: This expert opinion is a practical guide for dermatologists when handling psoriasis patients with these specific conditions.

Practical recommendations for systemic treatment in psoriasis according to age, pregnancy, metabolic syndrome, mental health, psoriasis subtype and treatment history (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis; part 1).

BACKGROUND: Impressive progress in new therapeutic options has been made for psoriasis. Treatments include topical steroids, phototherapy, conventional, synthetic disease-modifying drugs and an expanding list of biologics. OBJECTIVE: The primary objective of this work was to collect evidence for the creation of practice guidelines for systemic treatment of psoriasis (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis). METHODS: Evidence-based recommendations were formulated using a quasi-Delphi methodology after a systematic search of the literature and a consensus procedure involving 8 psoriasis experts. RESULTS: In this part, the use of systemic treatment in different age groups, during pregnancy, in metabolic syndrome, in patients with mental health problems, in different psoriasis subtypes and in previously systemically treated patients treatment is discussed. CONCLUSION: Guidance on therapeutic choice in specific clinical situations in psoriasis is provided in order to facilitate the decision-making in clinical practice.

Fever, Malaise, and Dyspnea in a Diabetic Heart Transplant Patient: A Case Report.

Patients with solid-organ transplants usually present at the emergency department with nonspecific symptoms. The physician should consider a great variety of syndromes and diseases, given the greater risk that solid-organ transplant patients carry because of immunosuppression and transplant-related conditions. Myocardial infarction caused by cardiac allograft vasculopathy must be always suspected and ruled out, even when initial symptoms do not orientate in that direction. We present a case that conjugates signs that can be present in different pathologies. It shows that fever is not always related to infection or rejection but could also appear in acute cardiac allograft vasculopathy. It emphasizes the need of a multi-disciplinary team led by a heart transplant specialist when dealing with this sort of clinical case.

Role of the HLA-C*06 allele in clinical response to ustekinumab: evidence from real life in a large cohort of European patients.

BACKGROUND: Little is known about the role of the HLA-C*06 allele in the response to psoriasis treatments. OBJECTIVES: To confirm the role of HLA-C*06 as a pharmacogenetic marker of response to ustekinumab in a new, large cohort of patients involving four European centres. METHODS: In this retrospective multicentre study we reviewed data of 255 patients with psoriasis genotyped for HLA-C*06 who started ustekinumab treatment between January 2014 and March 2015. The severity of psoriasis and response to treatment were evaluated using the Psoriasis Area and Severity Index (PASI) score at baseline and then at follow-up visits on weeks 4, 12, 28, 40 and 52. The primary end point was the proportion of patients achieving ≥ 50% reduction in PASI score (PASI 50) at week 4. A ≥ 75% reduction in PASI score (PASI 75) and a ≥ 90% reduction in the PASI score (PASI 90) after 12 weeks were secondary end points. RESULTS: At week 4, PASI 50 was seen in 71·7% of HLA-C*06-positive (C*06POS) and 35·2% of HLA-C*06-negative (C*06NEG) patients. At week 12, PASI 75 was reached by 69.1% of C*06POS patients and 40·5% of C*06NEG patients. After 52 weeks, PASI 75 was reached by 83.7% of C*06POS patients and 58.8% of C*06NEG patients. CONCLUSIONS: The results from our new, large cohort of European patients treated with ustekinumab in daily clinical practice confirm the role of HLA-C*06 as a potential predictor of response to ustekinumab.

Quality of Life According to Urgency Status in De Novo Heart Transplant Recipients.

INTRODUCTION: Elective heart transplantation (HTX) aims to improve physical ability, increase survival, and improve health-related quality of life (HRQoL) in patients with chronic heart failure. Nevertheless, most patients who undergo urgent HTX are previously healthy, and a transplant could be perceived as a limitation. The aim of this study is to compare HRQoL between elective and urgent heart transplant recipients. METHODS: Cohort study including patients undergoing heart transplantation between January 1998 and March 2012 in a single center. Patients with retransplantation or multiorgan transplantation were excluded. Clinical variables including comorbidities were collected. For assessment of HRQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ) was completed by the survivors on March 2013. Univariate analysis (Mann-Whitney U test) was performed. RESULTS: Questionnaires were collected from 95 of 106 elective recipients and 28 of 33 urgent recipients. Urgent heart recipients were younger, with more cardiovascular risk factors, and ischemic etiology was the leading cause of transplant. All domain results were higher in elective heart transplant recipients, but after univariate analysis only the punctuation of the self-efficacy domain remained superior in the elective HTX group (87.5 vs 79.7, P = .034). CONCLUSION: Both urgent and elective heart transplant patients reported a good HRQoL, and there were no significant differences between their scores.

Association of Presence of Band Cells and Toxic Neutrophils with Systemic Inflammatory Response Syndrome and Outcome in Horses with Acute Disease.

BACKGROUND: Band cells and toxic neutrophils are thought to indicate acute and severe systemic illness but no studies have investigated their importance in adult equine emergency admissions. OBJECTIVES: The objective of this study was to evaluate the association of band cells and toxic neutrophils with systemic inflammatory response syndrome (SIRS) and outcome in horses. ANIMALS: One hundred and five adult horses admitted on emergency basis to a private primary referral practice. METHODS: Prospective observational study with sample collection. All horses admitted on emergency basis over the study period were included in the study if they had a CBC and a blood smear collected on admission. RESULTS: The detection of band neutrophils on admission was associated with the SIRS status of the horse (RR = 2.80; 95% CI = 1.57-4.99; P < .001) and with poor outcome (RR = 1.88; 95% CI: 1.05-3.37; P = .038). Similarly, the presence of a neutrophil toxic grade higher than 3 was associated with SIRS (RR = 1.71; 95% CI: 1.03-2.82; P = .034) and death (RR = 2.34; 95% CI: 1.22-4.50, P = .007). The information gained from the blood smear review could not be captured by looking at only the WBC or neutrophil count. CONCLUSIONS AND CLINICAL IMPORTANCE: The microscopic review of blood smears from critically ill horses to detect band cells or neutrophil toxic change is valuable and could help in assessing disease severity and prognosis in adult equine emergency admissions.

Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease.

BACKGROUND: Chronic heart failure (CHF) is characterized by an inflammatory status with high levels of cytokines such as IL-6. We hypothesized that patients with CHF may develop immunosenescence due to inflammation and that this may be associated with a worse stage of the disease. METHODS AND RESULTS: We compared the immunological features of 58 elderly CHF patients (ECHF), 40 young CHF patients (YCHF), 60 healthy elderly controls (HEC) and 40 healthy young controls (HYC). We characterized leukocyte and lymphocyte subpopulations by flow cytometry, and IL-6 concentration by ELISA. The extent of CHF was classified according to functional and/or morphological criteria: New York Heart Association functional class, AHA/ACC heart failure stages, left ventricular ejection fraction, and left ventricular hypertrophy. CHF patients showed an increased number of leukocytes, neutrophils and monocytes, but a decreased number of lymphocytes. CHF patients had significantly lower levels of B-cells and CD4+ T-cells, increased NK-cells in YCHF, and increased CD8+ T-cells only in ECHF. CHF was associated with high differentiation in CD4+ and CD8+ T-lymphocyte subsets. Aging of T-lymphocyte subpopulations and high IL-6 levels were associated with a worse clinical status. IL-6 also correlated positively with the number of highly differentiated T-lymphocytes and with their accelerated aging. CONCLUSIONS: We conclude that CHF patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and IL-6 levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system.

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: calcineurin-inhibitors conversion or minimization?

BACKGROUND: In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS: In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS: Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION: In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Diagnostic yield of echocardiography in stroke: should we improve patient selection?

INTRODUCTION: Last year the European Society of Echocardiography published recommendations for the use of echocardiography in identifying potential sources of embolism as a cause of ischemic stroke in the absence of other cerebrovascular diseases. Both transthoracic echocardiography and transesophageal echocardiography play a fundamental role in the assessment, diagnosis and management of the embolic source. Due in part to the increased longevity of the population and improved survival of cardiac patients, we are now seeing a gradual increase in the application of echocardiographic studies as a diagnostic test. This has led us to critically analyse their performance in detecting various pathologies. OBJECTIVE: Our aim was to analyse the diagnostic yield of transthoracic echocardiography in patients with cerebrovascular accident in a tertiary hospital. MATERIAL AND METHODS: To this end, we retrospectively analysed all echocardiographic studies during 2010 requested from the Neurology Department with a diagnosis of stroke. We have studied the diagnostic yield of the test and its contribution to the etiological diagnosis based on major and minor echocardiographic criteria as recommended by the European Society of Echocardiography. RESULTS: We found major echocardiographic criteria in 6 patients (5%) with embolic stroke and in 2 (0.7%) non embolic, P=.005. In view of our results, the performance of transthoracic echocardiography in patients with embolic stroke has a low diagnostic yield, which leads us to question systematic use of this technique.

Steroid withdrawal during 5 years following heart transplantation, and the relationship between steroid dosage at 1-year follow-up and complications during the next 2 years: results from the RESTCO study.

BACKGROUND: Little information is available regarding the controversial issue of steroid withdrawal following heart transplantation (HT), or instead in the incidence of adverse steroid effects at dosages typically employed in Spain. METHODS: We analyzed the 5-year follow-up records of 1209 patients (82.5% men, aged ≥ 18 years) who underwent HT between 2000 and 2005 and survived at least 1 month in 13 Spanish centers. The incidences of first steroid withdrawal before 1, 3, and 5 years post-HT were expressed as Kaplan-Meier probability estimates. Three patient groups defined in accordance with steroid dosage at 1-year follow-up (0, ≤ 5, and >5 mg/d; groups A, B, and C, respectively) were compared with regard to the incidence of de novo hypertension, diabetes, and bone fractures over the following 2 years. RESULTS: The 5-year incidence of withdrawal was 28%, 21% of whom required reintroduction of steroids. Kaplan-Meier probabilities of withdrawal before 1, 3, and 5 years post-HT were 8.8% (95% confidence interval ([CI] 7.3%-10.7%), 27.8% (CI 25.2%-30.6%), and 30.2% (CI 27.5%-33.2%), respectively. At 1-year follow-up, 9.9% of patients were steroid-free, 28.9% were taking ≤ 5 mg/d, and 61.3% >5 mg/d. The 2-year incidence of de novo hypertension increased significantly (P = .012) from 13.5% to 29.6% to 35.3% in groups A, B, and C respectively. These groups did not differ significantly in regard to the 2-year incidence of diabetes or bone fractures. CONCLUSIONS: Reintroduction of steroids was required by 21% of the 28% of Spanish HT patients who has been weaned from steroids within 5 years of HT. The incidence of de novo hypertension between 1 and 3 years post-HT increased with steroid dosage at 1-year follow-up. De novo diabetes and bone fractures showed no similar significant association.

Effect of CYP3A5, CYP3A4, and ABCB1 genotypes as determinants of tacrolimus dose and clinical outcomes after heart transplantation.

BACKGROUND: Tacrolimus (Tac) is mainly metabolized by cytochrome P450 3A isoenzymes. In a cohort of heart transplant recipients, we investigated the effect of CYP3A5, CYP3A4, and ABCB1/MDR1 polymorphisms on Tac dose requirements and the risk of developing new-onset diabetes after transplantation (NODAT). METHODS: A total of 65 heart transplant recipients were genotyped for 3 single nucleotide polymorphisms (SNPs) in the CYP3A5 (SNP rs776746), CYP3A4 (SNP rs2740574), and ABCB1 (SNP rs104564). The mean Tac dose values were compared between the genotypes. RESULTS: CYP3A5 3 homozygotes (nonexpressers; n = 55, 85%) received significantly higher Tac dose compared with CYP3A5 1 carriers (expressers). No different NODAT frequencies were found between the genotypes. CONCLUSIONS: The CYP3A5 polymorphism was the main determinant of Tac dose requirements among heart transplant recipients. This common functional polymorphism had no influence on the risk of developing NODAT.

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

A protocol of trauma care in the emergency service including MDCT imaging.

Trauma is the principal cause of young peo ple's death. Care should be appropriate to the severity of the injuries and involves a multidisciplinary team around the clock. In this article, we examine a protocol of care based on ATLS (Advanced Trauma Life Support) recom mendations, including advances in imaging technology, which have greatly increased quality care in our institu tion. The protocol is based on patient stability and on injury mechanisms. The challenge is to avoid wasting time in the definitive treatment of lesions. Multi-detector computed tomogra phy (MDCT) has brought complete and rapid imaging in stable traumas but it shouldn't delay immediate surgical operations. When patients are unstable despite reanima tion, three important x-rays are taken right on the stretch er (pelvis, neck, and chest) before going into surgery. The head of the trauma team makes a decision on the pertinence of such procedure.

Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients--a large European trial.

We compared efficacy and safety of tacrolimus (Tac)-based vs. cyclosporine (CyA) microemulsion-based immunosuppression in combination with azathioprine (Aza) and corticosteroids in heart transplant recipients. During antibody induction, patients were randomized (1:1) to oral treatment with Tac or CyA. Episodes of acute rejection were assessed by protocol biopsies, which underwent local and blinded central evaluation. The full analysis set comprised 157 patients per group. Patient/graft survival was 92.9% for Tac and 89.8% for CyA at 18 months. The primary end point, incidence of first biopsy proven acute rejection (BPAR) of grade >/= 1B at month 6, was 54.0% for Tac vs. 66.4% for CyA (p = 0.029) according to central assessment. Also, incidence of first BPAR of grade >/= 3A at month 6 was significantly lower for Tac vs. CyA; 28.0% vs. 42.0%, respectively (p = 0.013). Significant differences (p < 0.05) emerged between groups for these clinically relevant adverse events: new-onset diabetes mellitus (20.3% vs. 10.5%); post-transplant arterial hypertension (65.6% vs. 77.7%); and dyslipidemia (28.7% vs. 40.1%) for Tac vs. CyA, respectively. Incidence and pattern of infections over 18 months were comparable between groups, as was renal function. Primary use of Tac during antibody induction resulted in superior prevention of acute rejection without an associated increase in infections.

Dynamical and cellular electrophysiological mechanisms of ECG changes during ischaemia.

The interpretation of normal and pathological electrocardiographic (ECG) patterns in terms of the underlying cellular and tissue electrophysiology is rudimentary, as the existing theories rely on geometrical aspects. We relate effects of sub-endocardial ischaemia on the ST-segment depression in ECG to patterns of transmural action potential propagation in a one-dimensional virtual ventricular wall. Our computational study exposes two electrophysiological mechanisms of ST depression: dynamic-predominantly positive spatial gradients in the membrane potential during abnormal repolarization of the wall, produced by action potential duration changes in the ischaemic region; and static-a negative spatial gradient of the resting membrane potential between the normal and ischaemic regions. Hyperkalaemia is the major contributor to both these mechanisms at the cellular level. These results complement simulations of the effects of cardiac geometry on the ECG, and dissect spatio-temporal and cellular electrophysiological mechanisms of ST depression seen in sub-endocardial ischaemia.

[Emergency practice: specifics in the management of complex multiple trauma]. / Pratique d'urgence: particularités dans la prise en charge des polytraumatisés complexes.

Almost twenty years ago, Trunkey showed that deaths due to trauma followed a trimodal distribution over time. Half of these deaths were delayed by at least one to two hours after the initiating insult. This interval (the "golden hour") can be exploited, especially in specialized trauma centers (where the most severely injured patients are cared for), to aggressively treat these patients, thereby reducing morbidity and mortality. In Belgium, this hierarchy of trauma care centers is non-existent; patients are distributed within the healthcare system randomly, depending on the localisation of the accident and the directives of the unified "100" call centre. Because this limits the number of cases any one centre treats, this type of arrangement acts to inhibit the acquisition of competency in the handling of these complex patients. The relative lack of experience of individual emergency departments leads to difficulties in establishing diagnostic and treatment priorities for the most severely injured trauma victims. The approach to these patients must follow very precise guidelines, established scientifically in order to minimize the impact of the injury on life and maximize chances of satisfactory functional recovery. In this paper, we describe the general principles of the initial approach to victims of complex multiple trauma.