Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey.

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non-ST- and ST-elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10-year follow-up period (2003-2013). Twenty ACS episodes occurred among 19 patients [rate, 0.8% (95% CI 0.4, 1.2)]. Seven patients (37%) were aged <50 years; 10 (53%) had ≥3 CRFs. In 5/20 episodes (25%), the initial ACS management protocol was altered because of the bleeding disorder. None of the eight patients with severe haemophilia underwent coronary artery bypass grafting (CABG), compared with 54.5% of patients with non-severe disease (P = 0.02). Revascularization with percutaneous coronary intervention (PCI) or CABG was rated successful in 13/13 cases, with no excessive bleeding during initial management. During chronic exposure to antiplatelet agents, secondary haemophilia prophylaxis was more prevalent in patients with severe haemophilia compared with non-severe haemophilia (85.7% vs. 30%, P = 0.05). No ACS-related deaths occurred during initial management, but one patient with severe haemophilia A died of undetermined cause 36 months after the ACS event while on aspirin therapy. ACS occurs even among relatively younger PWH, typically in association with multiple CRFs. Revascularization with PCI/CABG is feasible, and antiplatelet agents plus secondary prophylaxis appears to be well tolerated in selected PWH with ACS.

Epidemiology of bloodstream infections in a Scottish haemodialysis population with focus on vascular access method.

BACKGROUND: Infection is the second highest cause of mortality in end-stage renal disease, with a significant proportion relating to haemodialysis (HD) vascular access-related infection (VARI). AIM: To report the rate and antimicrobial resistance (AMR) of all-source bloodstream infections (BSIs) by vascular access type in a Scottish HD cohort. METHODS: Retrospective analysis was undertaken of data on adult patients attending seven HD units during 2017. Total HD days for each vascular access type were calculated. BSIs were analysed with rates expressed per 1000 HD days. AMR was verified using health board microbiology databases. FINDINGS: Excluding contaminant organisms, there was an overall BSI rate of 0.57 per 1000 HD days. The highest all-source and vascular access-related infection (VARI) BSI rates per 1000 HD days were in the non-tunnelled central venous catheter (CVC) group (3.11 and 2.07 respectively), followed by tunnelled CVC (1.10 and 0.67), arteriovenous graft (0.51 and 0.31), and finally arteriovenous fistula (0.29 and 0.02). The non-VARI BSI rates were lowest in the arteriovenous graft group. Staphylococci comprised the majority of events, with Staphylococcus aureus implicated in 29%. Gram-negative BSIs were prevalent, particularly in CVC groups, and associated with higher mortality. Multidrug-resistant (MDR) S. aureus and carbapenem resistance were relatively low. MDR Gram-negatives were high compared with the Scottish population. CONCLUSION: Arteriovenous fistula access is confirmed as having lowest all-source and VARI BSI rates, and arteriovenous graft access the lowest non-VARI BSI rates. Staphylococci remain the prevailing genus; however, the contributions of Gram-negative BSIs, the higher mortality, and proportion of MDR organisms in this group are notable.

A prospective randomized controlled study of two fluid regimens in the initial management of septic shock in the emergency department.

OBJECTIVES: To compare the impact of 40 mL/kg of fluid over 15 minutes followed by dopamine and further titration of therapy to achieve therapeutic goals (study protocol) versus 20 mL/kg over 20 minutes up to a maximum of 60 mL/kg over 1 hour followed by dopamine (control protocol) in septic shock. DESIGN AND SETTING: Prospective randomized controlled study in the emergency department of a public hospital in India. PATIENTS: One hundred forty-seven children older than 1 month presenting with septic shock were enrolled into the study. OUTCOME MEASURES: Hospital mortality (primary outcome), 72-hour survival, achievement of therapeutic goals of shock resolution, incidence of hypoxia, hepatomegaly, intubation at 20, 40, and 60 minutes (secondary outcomes) were compared between the arms. RESULTS: Seventy-four and 73 children were assigned to the study and control group, respectively. Overall mortality was 17.6%, 26 deaths with 13 in each arm. Mortality in the study cohort was lower than our historical mortality of 50% (P<0.0001), 95% confidence interval (CI), 11.9-24.8. Cumulative survival at 72 hours was 72.5% (95% CI, 58.9-86.1) and 77.6% (95% CI, 66.0%-89.2%) in the control and study groups, respectively. Resolution of shock in the emergency department was associated with survival odds ratio (OR) 9.2 (95% CI, 2.1-40.8). Rapidity of achieving therapeutic goals was not significantly different between groups. Intubation rates were also the same (46.5% in the control group versus 55% in the study group; P=0.28). At 20 minutes, 35.6% of the control group and 70% of the study group had hepatomegaly (P<0.01). CONCLUSION: There was no difference in the overall mortality, rapidity of shock resolution, or incidence of complications between the groups. The occurrence of hepatomegaly at 20 minutes following 40 mL/kg is of concern in settings with limited access to post-resuscitation ventilator care.

Centrally inserted external catheters and totally implantable ports for the delivery of chemotherapy: a systematic review and meta-analysis of device-related complications.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the risks of complications (infectious and non-infectious) including the need for device removal associated with centrally inserted external catheters compared with totally implantable ports in patients undergoing chemotherapy. METHODS: Relevant major electronic databases were searched from inception to December 2012. All randomized controlled trials (RCT) and observational studies that compared centrally inserted external catheters with totally implantable ports in patients undergoing chemotherapy were included in the systematic review. Meta-analysis was carried out to estimate the odds ratios of device-associated complications, including infection, non-infectious complications and device removal associated with external catheters relative to implantable ports. RESULTS: Overall, five RCTs and 25 observational studies were included in the study. The studies were heterogeneous, and included adults and children, with different types of cancer, undergoing chemotherapy. Based on the pooled estimates from included studies, external catheters were associated with approximately a three to four-fold increase in the risks of infections, non-infectious complications and device removal compared implantable ports. CONCLUSION: The findings of this study showed that totally implantable ports are superior to external catheters in terms of catheter-associated complications. However, a formal health technology assessment on the clinical and cost-effectiveness of the use of implantable ports compared with external catheters is needed to inform policy makers of the relative value of investing in totally implantable devices compared with external catheters.

Rituximab as first-line treatment for the management of adult patients with non-severe hemophilia A and inhibitors.

BACKGROUND: The role of immunosuppression in the management of patients with congenital hemophilia and inhibitors is uncertain. The use of rituximab has been limited to case reports and case series. In most reports, rituximab was used as second-line or third-line treatment following failure of conventional immune tolerance induction therapy, and more commonly in pediatric patients. OBJECTIVES: The objective of this study was to describe our experience with rituximab for the eradication of factor VIII inhibitors in adult patients with non-severe hemophilia A. PATIENTS: We retrospectively reviewed the medical records of adult patients with non-severe hemophilia A and a diagnosis of FVIII inhibitor treated with rituximab (four weekly doses of 375 mg m(-2) ) as first-line treatment at our hemophilia center. RESULTS: We identified nine consecutive adult patients with hemophilia A (moderate, n = 5; mild, n = 4) at our institution between 2000 and 2013, with a median age of 54 years (range, 24-77 years) at the time of inhibitor diagnosis. No patient received concomitant immune tolerance induction therapy. All nine patients had successful eradication of FVIII inhibitors. The median time from the first dose of rituximab to a clinical response was 95 days (range, 12-278 days). The median follow-up was 56 months (range, 13-139 months). Following inhibitor eradication, eight patients were rechallenged with FVIII concentrates. Two patients developed inhibitor recurrence associated with surgery. CONCLUSION: This case series demonstrates that rituximab is a useful first-line treatment to achieve sustained inhibitor eradication in adult patients with non-severe hemophilia A.

Posterior reversible encephalopathy syndrome unmasking acute glomerulonephritis.

Posterior reversible encephalopathy syndrome (PRES) is a recently described condition, wherein there is vasogenic oedema, seen on neuroimaging, predominantly over the parieto occipital regions of the cerebrum. Though, as the name implies, the condition is reversible, there may be fatalities and neurological sequelae. We are reporting a 9-year-old female child in whom the typical clinical and neurological findings of PRES were caused by an atypical presentation of acute glomerulonephritis.

Music during interventional radiological procedures, effect on sedation, pain and anxiety: a randomised controlled trial.

OBJECTIVE: To assess the effects of playing patient-selected music during interventional procedures on (1) the doses of sedation and analgesia and (2) anxiety levels. METHODS: Patients undergoing interventional radiological procedures were randomised to either the intervention (music) or the control (no music) group. Patients in the intervention group had music of their choice played via headphones during the procedure. The primary outcomes were reductions in the doses of drugs for sedation (midazolam) and analgesia (fentanyl). Anxiety levels were assessed both before and after the procedure using the validated State Anxiety Inventory. Mean pulse rate and average of mean blood pressures were also recorded before and during the procedures as surrogate indicators of anxiety levels. RESULTS: 100 patients were randomised in a 1:1 ratio. There were 58 males and 42 females, with a mean age of 58 years. Sedation was required in 21 (42%) patients in the music group compared with 30 (60%) patients in the control group (p=0.046). The mean [standard deviation (SD)] midazolam dose was 2.1 mg (2.3 mg) in the control group and 1.3 mg (2.2 mg) in the music group (p=0.027). The mean (SD) fentanyl dose was 29 mg (40 mg) in the control group and 18 mg (34 mg) in the music group (p=0.055). There was no significant effect of music on the change from baseline in anxiety levels (p=0.74), pulse rate (p=0.56) or blood pressure (p=0.34). CONCLUSION: Sedation requirements are significantly reduced by playing self-selected music to the patient during interventional radiology procedures. By lowering sedation during interventional radiology, music makes the procedure safer. It also contributes favourably to the overall patient experience.

Day-case peripheral angioplasty using nurse-led admission, discharge, and follow-up procedures: arterial closure devices are not necessary.

AIM: To audit the safety of day-case peripheral arterial intervention without the use of arterial-closure devices using nurse-led admission, discharge, and follow-up procedures. MATERIALS AND METHODS: Patients referred for elective, peripheral vascular intervention were selected for day-case care according to pre-determined criteria using telephone triage. Post-procedure haemostasis was achieved using manual compression. After 3h bed-rest, patients were mobilized and discharged at 5h. Patients were contacted by telephone next working day to audit complications. RESULTS: One hundred and eighty-three elective day-case peripheral interventions were performed over 2 years, predominantly using 6 F sheaths. No closure devices were used. Five patients (2%) returned to the department because of persistent groin symptoms the next day. One of these had a false aneurysm. Four required no further treatment. A single patient returned at day 6 with a delayed false aneurysm. CONCLUSION: Day-case peripheral vascular intervention can be safely performed in appropriately selected patients without the use of arterial closure devices. Specialist radiology nurses have a major role in the counselling, care, and follow-up of these patients.

Potential biomarkers of an exaggerated response to endotoxemia.

Serial plasma protein analysis was used to study the acute plasma proteome response to endotoxemia (presence of toxic bacterial products called endotoxins in the blood stream). Plasma samples from healthy volunteers before and multiple time points up to 24 h following administration of low-dose endotoxin were evaluated. Plasma protein profiles were obtained by rapid extraction of whole plasma followed by analysis with matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The profiles were unique to each individual and stable over the time of the experiment. Administration of low-dose endotoxin caused profound change in six of 18 individuals. At 8 h many proteins showed quantitative oxidation, in addition to the appearance of new components and disappearance of common baseline components. An exceptionally intense new component at 4154 mass units was identified as the activation peptide of C1 esterase inhibitor. While recovery of baseline protein structure was nearly complete by 24 h, serum amyloid A, an acute-phase reactant, was still increasing and minor profile changes persisted. Clinical features did not distinguish these extreme responders from others, suggesting that plasma proteome changes offered unique insights into and potential biomarkers of subclinical events following endotoxin exposure.

Correlation of a T45S variant of apolipoprotein C1 with elevated BMI in persons of American Indian and Mexican ancestries.

Obesity and diabetes are serious health problems for Americans and especially for those with American Indian or Mexican ancestry. A preliminary survey by protein analysis rather than classical nucleic acid sequencing methods has suggested a correlation between a newly discovered T45S variant of apolipoprotein C1 (ApoC1), found only in persons with American Indian or Mexican ancestry, and elevated body mass index (BMI). American Indians with the S45 ApoC1 variant (n=36) had an average of 9% higher BMI than those who had only T45 ApoC1 (n=192, P=0.029). Elevated rates of diabetes were reported for parents of subjects with the S45 protein (P=0.006). In five gender-matched sibling pairs, persons with Mexican ancestry showed a 1.34-fold higher BMI for those with S45 ApoC1 (P=0.022). This protein may contribute to the elevated rates of diabetes in relevant ethnic groups and might be more common in isolated populations.