Use Of Clinical Factors Research Articles

Factors predicting long-term outcomes following physiotherapy in patients with subacromial pain syndrome: a secondary analysis

BackgroundAlthough patients with shoulder complaints are frequently referred to physiotherapy, putative predictive factors for outcomes are still unclear. In this regard, only a limited amount of scientific data for patients with subacromial pain syndrome exist, with inconsistent results. An improved knowledge about the ability of baseline variables to predict outcomes could help patients make informed treatment decisions, prevent them from receiving ineffective treatments, and minimize the risk of developing chronic pain.AimThe aims of this secondary longitudinal analysis are threefold: First, to investigate baseline differences between patients with and without successful long-term outcomes following physiotherapy. Second, to compare the predictive ability of two sets of putative predictive variables on outcomes, one based on the literature and one based on the data of the original trial. Third, to explore the contribution of short-term follow-up data to predictive models.MethodsDifferences between responders and nonresponders were calculated. The predictive ability of variables defined through literature and of variables based on the Akaike Information Criterion (AIC) from the original trial dataset on the Shoulder Pain and Disability Index and the Patients’ Global Impression of Change at the one-year follow-up were analyzed. To test the robustness of the results, different statistical models were used. To investigate the contribution of follow-up data to prediction, short-term data were included in the analyses.ResultsA sample of 87 patients with subacromial pain syndrome was analyzed. 77% (n = 67) of these participants were classified as responders. Higher expectations and short-term change scores were positive, and higher fear avoidance beliefs, greater baseline disability and pain levels were negative predictors of long-term outcomes in patients with subacromial pain syndrome.ConclusionsAlthough our results are in line with previous research and support the use of clinical factors for prediction, our findings suggest that psychological factors, especially patient expectations and fear avoidance beliefs, also contribute to long-term outcomes and should therefore be considered in the clinical context and further research. However, the hypotheses and recommendations generated from our results need to be confirmed in further studies due to their explorative nature.Trial registrationThe original trial was registered at Current Controlled Trials under the trial registration number ISRCTN86900354 on March 17, 2010.

A new anticoagulant strategy: the factor XI inhibitors

In the last 10 years the introduction of the direct oral anticoagulants (DOACs) has revolutionized the anticoagulant treatment, one of the cornerstones of the therapy for cardiovascular diseases. Thanks to their efficacy at least not inferior compared to vitamin K antagonists and their better safety profile, particularly with regard to intracranial bleeding, DOACs are now the first choice for the prevention of cardioembolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism (VTE). Other areas of clinical use for DOACs include the prevention of VTE in orthopedic and oncology surgery and in outpatient cancer patients treated with anticancer therapy, or the use of low-dose in association with aspirin in patients with coronary or peripheral artery disease.An increased risk of gastrointestinal bleeding has been reported for some DOACs. In addition, DOACs have also experienced some failures including stroke prevention in patients with mechanical prosthetic valves or rheumatic diseases and VTE therapy in patients with antiphospholipid antibody syndrome. Also, no data are available on DOACs in some particular areas, including severe renal impairment and thrombocytopenia.In recent years, the clinical use of factor XI and factor XII inhibitors has been proposed. Currently, factor XI inhibitors have more clinical data than factor XII inhibitors. This article will report the rationale for the clinical use and the main evidences currently available on factor XI inhibitors.

Usefulness of clinical factors for diagnosing and differentiating types of testicular malposition in boys: A retrospective study.

To investigate useful objective variables and factors supporting the diagnosis of retractile testis and cryptorchidism by primary care providers, including urologists. This retrospective study included 512 boys diagnosed with retractile testis or cryptorchidism at our institute. Boys with retractile testis were followed up and underwent orchiopexy once the testis became undescended, while boys with cryptorchidism underwent orchiopexy immediately. We investigated trends in the prevalence of testicular malposition and explored useful diagnostic factors for retractile testis and cryptorchidism. Of 512 boys, 199 were diagnosed with retractile testis and 313 were diagnosed with cryptorchidism. Comparison of clinical information between retractile testis and cryptorchidism showed that age at diagnosis, laterality, and location of the testis were significantly different between the groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The comparison of surgical information also showed that epididymal abnormality and state of processus vaginalis is patency or closure were significantly different between the groups (P = 0.0088 and P = 0.0003, respectively). Multivariate analysis showed that diagnosis at age 0-1 years, unilaterality, and canalicular testis were predictive factors for cryptorchidism (P = 0.001, P < 0.0001, and P < 0.0001, respectively). Age at diagnosis, laterality, and location of the testis could be factors to aid the diagnosis of retractile testis and cryptorchidism.

Radiomics Analysis of PET and CT Components of 18F-FDG PET/CT Imaging for Prediction of Progression-Free Survival in Advanced High-Grade Serous Ovarian Cancer.

ObjectiveTo investigate radiomics features extracted from PET and CT components of 18F-FDG PET/CT images integrating clinical factors and metabolic parameters of PET to predict progression-free survival (PFS) in advanced high-grade serous ovarian cancer (HGSOC).MethodsA total of 261 patients were finally enrolled in this study and randomly divided into training (n=182) and validation cohorts (n=79). The data of clinical features and metabolic parameters of PET were reviewed from hospital information system(HIS). All volumes of interest (VOIs) of PET/CT images were semi-automatically segmented with a threshold of 42% of maximal standard uptake value (SUVmax) in PET images. A total of 1700 (850×2) radiomics features were separately extracted from PET and CT components of PET/CT images. Then two radiomics signatures (RSs) were constructed by the least absolute shrinkage and selection operator (LASSO) method. The RSs of PET (PET_RS) and CT components(CT_RS) were separately divided into low and high RS groups according to the optimum cutoff value. The potential associations between RSs with PFS were assessed in training and validation cohorts based on the Log-rank test. Clinical features and metabolic parameters of PET images (PET_MP) with P-value <0.05 in univariate and multivariate Cox regression were combined with PET_RS and CT_RS to develop prediction nomograms (Clinical, Clinical+ PET_MP, Clinical+ PET_RS, Clinical+ CT_RS, Clinical+ PET_MP + PET_RS, Clinical+ PET_MP + CT_RS) by using multivariate Cox regression. The concordance index (C-index), calibration curve, and net reclassification improvement (NRI) was applied to evaluate the predictive performance of nomograms in training and validation cohorts.ResultsIn univariate Cox regression analysis, six clinical features were significantly associated with PFS. Ten PET radiomics features were selected by LASSO to construct PET_RS, and 1 CT radiomics features to construct CT_RS. PET_RS and CT_RS was significantly associated with PFS both in training (P <0.00 for both RSs) and validation cohorts (P=0.01 for both RSs). Because there was no PET_MP significantly associated with PFS in training cohorts. Only three models were constructed by 4 clinical features with P-value <0.05 in multivariate Cox regression and RSs (Clinical, Clinical+ PET_RS, Clinical+ CT_RS). Clinical+ PET_RS model showed higher prognostic performance than other models in training cohort (C-index=0.70, 95% CI 0.68-0.72) and validation cohort (C-index=0.70, 95% CI 0.66-0.74). Calibration curves of each model for prediction of 1-, 3-year PFS indicated Clinical +PET_RS model showed excellent agreements between estimated and the observed 1-, 3-outcomes. Compared to the basic clinical model, Clinical+ PET_MS model resulted in greater improvement in predictive performance in the validation cohort.ConclusionPET_RS can improve diagnostic accuracy and provide complementary prognostic information compared with the use of clinical factors alone or combined with CT_RS. The newly developed radiomics nomogram is an effective tool to predict PFS for patients with advanced HGSOC.

Factor VIII Inhibitor Bypassing Activity (FEIBA) Reversal for Apixaban and Rivaroxaban in Patients With Acute Intracranial and Nonintracranial Hemorrhage.

The clinical use of factor VIII inhibitor bypassing activity (FEIBA) for factor Xa (FXa) inhibitor reversal is derived from small studies with notable variation in patient eligibility for use, dosage regimens, concurrent supportive care, and outcome measures. Consequently, additional effectiveness and safety data are warranted to expand the literature evaluating FEIBA for FXa inhibitor reversal. This study sought to determine the incidence of observed effective hemostasis within 24 hours of post-FEIBA® administration as well as in-hospital and 30-day post-discharge incidences of thromboembolic event (TEE) and mortality between apixaban and rivaroxaban in the intracranial hemorrhage (ICH) and non-ICH populations. This case series evaluated patients between January 1, 2014 through July 1, 2019 who received at least one FEIBA® dose for apixaban or rivaroxaban reversal secondary to acute ICH or non-ICH. Patient demographics, FEIBA® dosages, adjunct treatments, effectiveness, and safety outcomes were retrospectively collected from electronic medical record review. Modified hemostasis outcomes, adapted from criteria previously published by Sarode et al., TEE, and mortality between apixaban and rivaroxaban in the ICH and non-ICH populations were evaluated. Among the 104 patients evaluated, 62 received apixaban and 42 rivaroxaban. Thirty apixaban and 25 rivaroxaban users experienced ICH, whereas 32 apixaban and 17 rivaroxaban users experienced non-ICH. Among the combined ICH and non-ICH populations, effective hemostasis occurred in 89%, TEE in 8%, and mortality in 13%. No statistically significant differences were observed within ICH and non-ICH populations receiving apixaban or rivaroxaban regarding effective hemostasis, TEE, or mortality. The combined ICH and non-ICH overall rates of effective hemostasis, TEE, and mortality were comparable to preexisting studies of FEIBA for factor Xa inhibitor reversal. The limitations inherent to the study design warrant a randomized controlled trial with an active comparator to confirm these observations.

Can we predict patient outcome before extracorporeal membrane oxygenation for refractory cardiac arrest?

BackgroundRefractory cardiac arrest resistant to conventional cardiopulmonary resuscitation (C-CPR) has a poor outcome. Although previous reports showed that extracorporeal cardiopulmonary resuscitation (E-CPR) can improve the clinical outcome, there are no clinically applicable predictors of patient outcome that can be used prior to the implementation of E-CPR. We aimed to evaluate the use of clinical factors in patients with refractory cardiac arrest undergoing E-CPR to predict patient outcome in our institution.MethodsThis is a single-center retrospective study. We report 112 patients presenting with refractory cardiac arrest resistant to C-CPR between January 2012 and November 2017. All patients received E-CPR for continued life support when a cardiogenic etiology was presumed. Clinical factors associated with patient outcome were analyzed. Significant pre-ECMO clinical factors were extracted to build a patient outcome risk prediction model.ResultsThe overall survival rate at discharge was 40.2, and 30.4% of patients were discharged with good neurologic function. The six-month survival rate after hospital discharge was 36.6, and 25.9% of patients had good neurologic function 6 months after discharge. We stratified the patients into low-risk (n = 38), medium-risk (n = 47), and high-risk groups (n = 27) according to the TLR score (low-flow Time, cardiac arrest Location, and initial cardiac arrest Rhythm) that we derived from pre-ECMO clinical parameters. Compared with the medium-risk and high-risk groups, the low-risk group had better survival at discharge (65.8% vs. 42.6% vs. 0%, p < 0.0001) and at 6 months (60.5% vs. 38.3% vs. 0%, p = 0.0001). The low-risk group also had a better neurologic outcome at discharge (50% vs. 31.9% vs. 0%, p = 0.0001) and 6 months after discharge (44.7% vs. 25.5% vs. 0%, p = 0.0003) than the medium-risk and high-risk groups.ConclusionsPatients with refractory cardiac arrest receiving E-CPR can be stratified by pre-ECMO clinical factors to predict the clinical outcome. Larger-scale studies are required to validate our observations.

Radium 223 treatment in metastatic prostate cancer: Exploring use of clinical factors for prognostication in routine practice.

e17550 Background: Skeletal metastases are seen in over 90% of metastatic castrate resistant prostate cancer (mCRPC) patients during the course of their disease and is a major cause for significant morbidity and mortality in them. Radium 223 (Ra-223) is a bone seeking calcium mimetic alpha emitter that has demonstrated significant improvement in survival and reduction in skeletal related events (ALSYMPCA trial). Ra-223 treatment was well tolerated and showed benefit before or after chemotherapy. In this study we aimed to assess efficacy of Ra-223 in mCRPC patients treated in our centre and their survival in relation to some common clinical variables that may assist patient selection in routine clinical practice. Methods: We conducted a retrospective audit of mCRPC patients treated with Ra-223 from June 2015 – December 2019. We analysed treatment outcomes and use of Haemoglobin (Hb), Albumin (Alb) and Alkaline Phosphatase (ALP) as potential prognostic factors. Results: There were 46 patients in total with a median age of 76 years (range; 56-90) and 26% were ≥80 years of age. The median follow-up was 10 months (range; 2-38 months). Median baseline PSA was 103.7 (range; 7.2 - 2534) and median baseline ALP was 188 U/L (range; 51 - 2262). Ra-223 was given as 1st or 2nd line treatment in 65% of our patients. Median number of cycles of Ra-223 administered was 4 and 41% of patients completed 6 cycles of treatment. Biochemical response (drop in PSA &gt; 50%) was only seen in 11% of patients but good response in ALP levels (drop in ALP &gt; 50%) was seen in 35%. Median overall survival (OS) was 10 months. Median OS for patients who received Ra-223 as 1st or 2nd line vs subsequent line was 13 and 8.5 months respectively. Median OS for patients with Haemoglobin (Hb) ≥12gm/dl) and lower Hb were 11 and 7 months respectively. Patients with normal albumin at baseline had median OS of 15 months compared to 6 months for those with low albumin. Favourable prognostic group patients (Normal Hb, Normal albumin at baseline and normal ALP after treatment) had a median OS of 31 months compared to 9 months for those in less favourable group. Patients who completed at least 5 cycles had a better survival (13 vs 8.5 months). Fractures were reported in 3 patients (6.5%). Conclusions: Ra-223 treated patients in our centre had a reasonable survival despite having a larger proportion of elderly population compared to the registration trial. Ra-223 treatment seems to be more effective when given at earlier lines in mCRPC setting. Pre-treatment Albumin lower than normal seems to be a predictor for poor overall survival.

Predicting the effect of 5-fluorouracil-based adjuvant chemotherapy on colorectal cancer recurrence: A model using gene expression profiles.

ABSTRACTIt is critical to identify patients with stage II and III colorectal cancer (CRC) who will benefit from adjuvant chemotherapy (ACT) after curative surgery, while the only use of clinical factors is insufficient to predict this beneficial effect. In this study, we performed genetic algorithm (GA) to select ACT candidate genes, and built a predictive model of support vector machine (SVM) using gene expression profiles from the Gene Expression Omnibus database. The model contained four ACT candidate genes (EDEM1, MVD, SEMA5B, and WWP2) and TNM stage (stage II or III). After using Subpopulation Treatment Effect Pattern Plot to determine the optimal cutoff value of predictive scores, the validated patients from The Cancer Genome Atlas database can be divided into the predictive ACT‐benefit/‐futile groups. Patients in the predictive ACT‐benefit group with 5‐fluorouracil (5‐Fu)–based ACT had significantly longer relapse‐free survival (RFS) compared to those without ACT (P = .015); However, the difference in RFS in the predictive ACT‐futile group was insignificant (P = .596). The multivariable analysis found that the predictive groups were significantly associated with the effect of ACT (P interaction = .011). Consequently, we developed a predictive model based on the SVM and GA algorithm which was further validated to define patients who benefit from ACT on recurrence.

Use of clinical factors to predict imaging appearance of bony metastases in colorectal cancer: A retrospective analysis.

e15152Background: The purpose of this study was to evaluate imaging features of bony metastases in patients with CRC and to assess if initial tumor stage and serum biomarkers (CEA levels) can predi...

Prediction of Primary Treatment Outcome Using Gene Expression Profiling of Pre-Treatment Biopsies Obtained from Childhood and Adolescent Hodgkin Lymphoma Patients

Introduction: Hodgkin lymphoma (HL) is a common malignancy of children and adolescents and is highly curable with a 5-year overall survival (OS) rate of > 97%, yet dose-intensified chemotherapy regimens in combination with radiation therapy come with a high cost in form of long-term toxicity and morbidity (Castellino et al., Blood 2011). This major clinical challenge has resulted in the evaluation of risk-adapted treatment regimens in clinical trials aiming to achieve the optimal equilibrium between high survival rates and prevention of treatment-related toxicity. However, risk stratification is currently limited to the use of clinical factors as there are no validated integral biomarkers that can be employed to either improve risk stratification or as surrogate markers of treatment outcome in pediatric HL. The aim of our study was to perform gene expression profiling (GEP) to uncover disease biology underlying treatment response and develop a prognostic model to tailor first-line therapy in pediatric HL.Methods: We selected 203 formalin-fixed, paraffin-embedded tissue (FFPET) specimens from patients enrolled in a randomized phase 3 clinical trial (AHOD0031) of the Children's Oncology Group (COG) based on the availability of archived FFPET blocks. That trial was designed to assess the value of early chemotherapy response for tailoring subsequent therapy in intermediate-risk pediatric HL. We performed GEP on RNA extracted from pre-treatment FFPET biopsies using NanoString technology and a customized codeset encompassing probes for 784 genes. These genes were either previously reported to be associated with prognosis and outcome in HL or represent the cellular diversity of the tumor microenvironment. Event free survival (EFS) and OS were estimated using the Kaplan-Meier method. Gene expression data were used to develop a predictive model for EFS using penalized Cox regression with parameters trained using leave-one-out cross-validation.Results: Of the 203 tissue samples obtained from the Biopathology Center at the Cooperative Human Tissue Network, 182 (89.7%) passed quality assurance testing, similar to the pass rate achieved for adult HL samples obtained from the Eastern Cooperative Oncology Group trial E2496 (Scott et al., JCO 2013). We applied our previously published 23-gene predictor for OS (Scott et al., JCO 2013), developed using biopsies from adult HL patients to our pediatric cohort. After calibrating the new codeset, 53 patients were classified as "high-risk" and 129 as "low-risk". Importantly, the model failed to predict inferior outcomes in the "high-risk" group (5-year OS 100% vs 95%, log-rank P = 0.125; 5-year EFS 82% vs 70%, log-rank P = 0.159), with patients in the "high risk" group trending to have superior outcomes than the "low risk" patients. Moreover, only 2 genes from this model, IFNG and CXCL11, were significantly associated with EFS in univariate Cox regression analysis (P = 0.003 and 0.048, respectively) but with inverse hazard ratios in the pediatric group compared to adult patients. Therefore, we sought to develop a novel EFS predictive model for pediatric patients treated in the AHOD0031 trial. Using univariate Cox regression we identified 79 genes significantly associated with EFS (raw P < 0.05). Using the expression of these 79 genes as the input to penalized Cox regression, we developed a 16-gene model to predict EFS in our training cohort. Using an optimized cut-off for the model score, 31% of patients were designated high-risk and had significantly inferior post-treatment outcome (5-year EFS 38% vs 89%, log-rank P < 0.0001). When multivariate analyses were performed including our EFS-model score, disease stage and initial treatment response as variables, only the model score was significantly associated with EFS (P < 0.0001, HR 11.3 (95% CI 5.5-23.4)).Conclusions: Failure of the GEP-based model developed in adult HL suggests distinct biology underlies treatment failure in the pediatric age group. We describe the development of a novel predictive model for EFS in intermediate-risk pediatric HL patients that will be validated in an independent cohort of patients treated in the AHOD0031 trial. Successful validation of the model may provide a clinically relevant biomarker for pediatric and adolescent HL patients allowing refinement of risk stratification and the combination of molecular and clinical risk factors at diagnosis. DisclosuresScott:Celgene: Consultancy, Honoraria; NanoString: Patents & Royalties: Inventor on a patent that NanoString has licensed.

Comparison of dosing algorithms for acenocoumarol and phenprocoumon using clinical factors with the standard care in the Netherlands

BackgroundIt has not been investigated how much the use of clinical factors in a dosing algorithm improves the percentage of time in therapeutic range (TTR). The present study aimed to compare the effect of dosing algorithms for acenocoumarol and phenprocoumon including clinical patient characteristics with standard care in the Netherlands.Setting: The pre-EU-PACT study, an observational study in the Netherlands, was used to obtain standard care data. Data from the Dutch patients in the EU-PACT trial (comparing the use of a clinical algorithm with and without genetic information) was used for the clinical dosing algorithm. MethodsFor both acenocoumarol and phenprocoumon, the percentage of time in, below and above therapeutic International Normalized Ratio (INR) range during 12weeks after treatment initiation were assessed in both studies. ResultsDuring the weeks 2-12, the clinical dosing algorithm of acenocoumarol (80 patients) led to a higher TTR (74.3% versus 68.0% in range 2.0-3.5, 95% Confidence interval [CI] difference: 0.5% to 11.8%), and a reduced percentage of time below INR 2 and above INR 3.5, compared with standard care (272 patients). For phenprocoumon, compared with standard care (484 patients), 80 patients treated by the dosing algorithm did not obtained a significantly higher TTR in range 2.0-3.5 or a lower percentage of time above 3.5, however, they spent more time with INR below 2. ConclusionThe use of a clinical dosing algorithm for acenocoumarol seemed to improve the quality of anticoagulation therapy during the treatment of initial 2-12 weeks. For phenprocoumon, there was no statistically difference in anticoagulation control.

Genetic and Clinical Factors Associated with Chronic Postsurgical Pain after Hernia Repair, Hysterectomy, and Thoracotomy: A Two-year Multicenter Cohort Study.

Chronic postsurgical pain (CPSP) has been linked to many surgical settings. The authors aimed to analyze functional genetic polymorphisms and clinical factors that might identify CPSP risk after inguinal hernia repair, hysterectomy, and thoracotomy. This prospective multicenter cohort study enrolled 2,929 patients scheduled for inguinal hernia repair, hysterectomy (vaginal or abdominal), or thoracotomy. The main outcome was the incidence of CPSP confirmed by physical examination 4 months after surgery. The secondary outcome was CPSP incidences at 12 and 24 months. The authors also tested the associations between CPSP and 90 genetic markers plus a series of clinical factors and built a CPSP risk model. Within a median of 4.4 months, CPSP had developed in 527 patients (18.0%), in 13.6% after hernia repair, 11.8% after vaginal hysterectomy, 25.1% after abdominal hysterectomy, and 37.6% after thoracotomy. CPSP persisted after a median of 14.6 months and 26.3 months in 6.2% and 4.1%, respectively, after hernia repair, 4.1% and 2.2% after vaginal hysterectomy, 9.9% and 6.7% after abdominal hysterectomy, and 19.1% and 13.2% after thoracotomy. No significant genetic differences between cases and controls were identified. The risk model included six clinical predictors: (1) surgical procedure, (2) age, (3) physical health (Short Form Health Survey-12), (4) mental health (Short Form Health Survey-12), (5) preoperative pain in the surgical field, and (6) preoperative pain in another area. Discrimination was moderate (c-statistic, 0.731; 95% CI, 0.705 to 0.755). Until unequivocal genetic predictors of CPSP are understood, the authors encourage systematic use of clinical factors for predicting and managing CPSP risk.

Use of Clinical Factors Alone in Tailoring Edoxaban Dose in Atrial Fibrillation

Edoxaban is a new target-specific oral anticoagulant that directly inhibits factor Xa (FXa). In a recent trial, edoxaban was shown to be noninferior to warfarin in preventing thromboembolic events and less likely to result in major bleeding or cardiovascular mortality in patients with atrial fibrillation. Now, in an industry-funded study, investigators analyzed whether edoxaban dose reductions made based on patient clinical characteristics resulted in reduced efficacy or safety in comparison with …

Pathology Consultation on Anticoagulation Monitoring

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Clinical use of factor VIII and factor IX concentrates.

Factor VIII (FVIII) and factor IX (FIX) are the cofactor and the pro-enzyme, respectively, acting in the tenase complex, a key mechanism of physiological haemostasis in which a phospholipide-dependent reaction produces the activation of factor X1. Mutations in the genes encoding for coagulation FVIII or IX, both located in the X chromosome, are responsible for haemophilia A and haemophilia B, respectively. These congenital bleeding disorders occur overall in approximately 1 in 5,000 male live births without racial predilection. However, the prevalence of haemophilia A is estimated 4–6 times higher than haemophilia B2–3. According to the residual endogenous FVIII/FIX concentrations, individuals with plasma factor levels 5–40 IU/dL are defined as moderate and mild haemophiliacs4. Although the bleeding phenotype is recognised to be heterogeneous and affected by many genetic and environmental factors5–6, this classification reflects rather closely the severity of clinical symptoms. Thus, patients with mild haemophilia experience excessive bleeding in the large majority of cases in response to surgery, other invasive procedures or major injuries4,7. On the other hand, patients with moderate haemophilia experience excessive bleeding after relatively minor trauma and those with severe haemophilia bleed spontaneously or after trivial trauma4,8. In the latter, haemarthrosis, particularly into hinged joints (ankle, knee, elbow), is largely the most frequently reported bleeding symptom8,9. Recurrent joint bleeding is associated with progressive joint morbidity (haemophilic arthropathy), leading to chronic pain and disability, that often warrant orthopaedic surgery and joint replacement10. Soft-tissue haematomas, mucosal, parenchimal and delayed post-surgical bleeding are less common manifestations, including life-threatening intracranial, neck-throat and gastro-intestinal haemorrhages8,9,11. Replacement therapy with intravenously delivered plasma-derived or recombinant FVIII and FIX concentrates, aimed at correcting the coagulation factor deficiency in the case of, or in order to prevent, bleeding is the cornerstone of management of patients with haemophilia A and haemophilia B, respectively. Indeed, these specific and viral-inactivated products are the source of choice of the missing proteins, in preference to fresh frozen plasma (for both factors), cryoprecipitate (for FVIII) or prothrombin complex concentrates (for FIX)11. The two forms of haemophilia have been usually considered indistinguishable from a clinical point of view and, consequently, as regards patterns of treatment. In this respect, most literature data have been achieved in cohorts of patients with haemophilia A and extrapolated to those with haemophilia B. However, according to recent findings, the bleeding tendency associated with FIX deficiency is likely to be less severe, with possible better long-term outcomes12. Plasma-derived FVIII concentrates may also contain variable amounts of von Willebrand factor (VWF), therefore some products are used in the management of those patients with von Willebrand disease with severe VWF deficiencies, in whom response to endogenous release by desmopressin is impossible or insufficient13. After a historical overview of treatment of haemophilia, this article will report the current clinical use of FVIII and FIX concentrates, also with reference to the Italian clinical scenario.

Usefulness of clinical factors in predicting outcomes of passive tilt tests in patients with syncope

Pretest patient selection affects the outcome of many diagnostic tests; this may be true for tilt-table tests. We assessed the impact of patient age, sex, and symptom burden on the outcome of passive tilt tests. Two hundred one patients with idiopathic syncope (87 men, aged 45 ± 20 years, median 5 fainting spells each) underwent passive, drug-free tilt tests for 45 minutes. Positive tests were defined as those ending in clinically reminiscent presyncope or syncope. Seventy-eight patients (39%) had a positive tilt test. Patients had a wide range of symptom burden, having a median 5 syncopal spells (interquartile range [IQR] 2.5 to 17.5) over a median 52.5 months (IQR 12 to 180) with a median frequency of 0.17 spells/month (IQR 0.042 to 0.67). None of these measures of symptom burden predicted tilt-test outcome (p = 0.33 to 0.46). In contrast, the age of the patient strongly predicted tilt-test outcome. The likelihood of a positive test was 75% in 36 patients <25 years old and 31% in 165 patients ≥25 years of age (p <0.0001, chi-square for 2 × 5 table). Younger patients also fainted more quickly: patients <25 years old fainted within 22 minutes of tilt and reached a clearly asymptotic value, whereas the likelihood of a positive tilt in patients ≥25 years old increased linearly with time, and did not reach an asymptote. Measures of symptom burden do not predict test outcome, and younger patients are more likely to faint during passive tilt testing.

Report of the Task Force on the Clinical Use of Factor IX Concentrates

Report of the Task Force on the Clinical Use of Factor IX Concentrates

The Use of Factor IX Concentrates for Patients with Conditions other than Factor IX Deficiency

Summary.The increasing availability of factor IX concentrates have extended their use in conditions other than factor IX deficiency and especially in combined acquired deficiencies of vitamin K dependent clotting factors.The occurrence of complications such as post‐transfusion hepatitis type B and thromboembolic episodes have prompted the International Committee on Thrombosis and Hemostasis to constitute a Task Force on the clinical use of factor IX concentrates.The various concentrates available and the basis for their method of preparation are listed. Their use in various pathological conditions other than factor IX deficiency and also the occurrence of complications in such conditions are reviewed.The conclusions and the recommendations on the indications and contraindications formulated by the Task Force on the clinical use of factor IX concentrates as issued following the 1974 Basel Meeting are summarized.

Small scale preparation and clinical use of factor IX-prothrombin complex.

Abstract. A. procedure is described for the preparation of a concentrate of factors II, VII, IX and X, using a modification of the method of Bruning and Loelioer, involving aluminium hydroxide adsorption of ACD plasma followed by phosphate elution and dialysis.The concentrate produced had an average factor IX activity of 7.4 U/ml with a yield of 61% and a purification of 34.5.Clinical trials in patients with either a congenital deficiency of factor IX or liver disease showed that the concentrate was well tolerated and was an effective haemostatic agent. The average factor IX response was 1.09% for each U/kg injected, giving a recovery of 48%.

Preparation and Clinical Use of Factor IX Concentrate PPSB According to Soulier

Summary. Preparation of factor IX concentrate according to Soulier proved to offer no technical difficulties. The factor IX concentration averaged 10–20 times that in an identical volume of normal plasma. Haemorrhagic complications in haemophilia B can be adequately controlled with this concentrate. The erythrocytes of donor blood used in the preparation of factor IX concentrate can be used for transfusion purposes.