Sudden cardiac death in hemodialysis patients: a comprehensive care approach to reduce risk

Sudden cardiac death is a major problem in hemodialysis patients, and our understanding of this disease is underdeveloped. The lack of a precise definition tailored for use in the hemodialysis population limits the reliability of epidemiologic reports. Efforts should be directed toward an accurate classification of all deaths that occur in this vulnerable population. The traditional paradigm of disease pathophysiology based on known cardiac risk factors appears to be inadequate to explain the magnitude of sudden cardiac death risk in chronic kidney disease, and numerous unique cofactors and exposures appear to determine risk in this population. Well-designed cohort studies will be needed for a basic understanding of disease pathophysiology and risk factors, and randomized intervention trials will be needed before best management practices can be implemented. This review examines available data to describe the characteristics of the high-risk patient and suggests a comprehensive common sense approach to prevention using existing cardiovascular medications and reducing and monitoring potential dialysis-related arrhythmic triggers. Other unproven cardiovascular therapies such as implantable cardioverter defibrillators should be used on a case-by-case basis, with recognition of the associated hazards that these devices carry among hemodialysis patients.     

Genetic analysis of structural proteins in the adsorption apparatus of bacteriophage epsilon 15

AIM: To probe the organizational structure of the adsorption apparatus of bacteriophage epsilon 15 (E15) using genetic and biochemical methodologyMETHODS: Hydroxylamine was used to create nonsense mutants of bacteriophage E15. The mutants were then screened for defects in their adsorption apparatus proteins, initially by measuring the concentrations of free tail spike proteins in lysates of cells that had been infected by the phage mutants under non-permissive growth conditions. Phage strains whose infected cell lysates contained above-average levels of free tail spike protein under non-permissive growth conditions were assumed to contain nonsense mutations in genes coding for adsorption apparatus proteins. These mutants were characterized by classical genetic mapping methods as well as automated sequencing of several of their genes. Finally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography were used to examine the protein compositions of the radioactive particles produced when the various mutants were grown on a non-permissive host cell in the presence of ³⁵S-methionine and co-purified along with E15wt phage on CsCl block gradients.RESULTS: Our results are consistent with gp4 forming the portal ring structure of E15. In addition, they show that proteins gp15 and gp17 likely comprise the central tube portion of the E15 adsorption apparatus, with gp17 being more distally positioned than gp15 and dependent upon both gp15 and gp16 for its attachment. Finally, our data indicates that tail spike proteins comprised of gp20 can assemble onto nascent virions that contain gp7, gp10, gp4 and packaged DNA, but which lack both gp15 and gp17, thereby forming particles that are of sufficient stability to survive CsCl buoyant density centrifugation.CONCLUSION: The portal ring (gp4) of E15 is bound to tail spikes (gp20) and the tail tube (gp15 and gp17); gp17’s attachment requires both gp15 and gp16.     

Implementing the National Hip Fracture Database: An audit of care

Background

Hip fractures are common injuries in the elderly, with significant associated morbidity and mortality rates. The National Hip Fracture Database (NHFD) was implemented to audit care according to national standards thus improving its clinical and cost-effectiveness.

Patients and methods

We retrospectively examined the care pathway for all hip fractures after its introduction at our centre over 1 year, with an audit of care according to the BOA-BGS ‘Blue Book’ guidelines. Data between the first (period 1: initial audit) and second (period 2: re-audit) six months of the study period were compared.

Results

There were 372 patients (28% male, 72% female) in total with 190 in period 1 and 182 in period 2. For all patients, the median age was 85 years (range 33–101) and the median time to surgery was 24.5 h (1–519.3), with 251 (67.5%) within 36 h. Surgical delay was mainly due to lack of theatre space (37.6%) and medical reasons (54.7%). The median length of stay was 11 days (2–92) and the inpatient mortality rate was 6.2% (23). When comparing the two study periods, there were significantly more patients undergoing falls (p < 0.01) and bone protection (p < 0.01) assessments in period 2. Lack of theatre space was a significantly less common (p < 0.01), with a significantly shorter median time to surgery (p = 0.01) and length of stay (p < 0.01) in period 2. More patients were discharged to rehabilitation units and the mortality rate was non-significantly lower in period 2 (7.4% vs. 5%). The best practice tariff was met in 45.3% and 70.3% (p < 0.001) of patients in periods 1 and 2 respectively providing a total income of £95230.00 (GBP).

Conclusions

Implementing the NHFD has led to an improvement the quality of hip fracture care according to national guidelines. More patients were assessed by an orthogeriatrician, with a shorter time to surgery and length of stay following re-audit. There is potential for an improvement in mortality rates as well as significant financial income for hospitals.     

Stroke management: updated recommendations for treatment along the care continuum

The Australian Clinical Guidelines for Stroke Management 2010 represents an update of the Clinical Guidelines for Stroke Rehabilitation and Recovery (2005) and the Clinical Guidelines for Acute Stroke Management (2007). For the first time, they cover the whole spectrum of stroke, from public awareness and prehospital response to stroke unit and stroke management strategies, acute treatment, secondary prevention, rehabilitation and community care. The guidelines also include recommendations on transient ischaemic attack. The most significant changes to previous guideline recommendations include the extension of the stroke thrombolysis window from 3 to 4.5 h and the change from positive to negative recommendations for the use of thigh-length antithrombotic stockings for deep venous thrombosis prevention and the routine use of prolonged positioning for contracture management.     

Window of opportunity treatment in breast cancer

Window of opportunity therapies, which involve short‐term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone‐receptor positive breast cancer, a 2‐week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision‐making regarding treatment options. Changes in short‐term biomarker endpoints such as cell proliferation measured by Ki‐67 can act as surrogate markers of long‐term outcomes. Paired tissues obtained pre‐ and post‐investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.     

Intracortical haematogenous osteomyelitis

We present an unusual case of haematogenous osteomyelitis in the diaphysis of the tibia of an adult leading to a subacute presentation with an extracortical abscess. Fluid from the abscess grew methicillin resistant Staphylococcus aureus (MRSA) on culture; MRSA with the same antibiogram had been grown from the patient’s blood seven years earlier following a bowel resection. Drainage of the abscess and curettage of the bone lesion together with appropriate antibiotic therapy led to resolution of the osteomyelitis.