Cord blood transplantation in Western Australia

Background/Aims: Thirty‐one umbilical cord blood transplants performed in Western Australia were retrospectively examined in order to document local experience and relevant prognostic factors. Three cord units were from human leucocyte antigen‐matched siblings and the remainder were unrelated single (n= 22) or double (n= 6) cord blood transplants. Methods: Twenty patients were transplanted for malignant conditions and 11 for non‐malignant conditions. Cord units contained a median of 5.6 × 10⁷ total nucleated cells/kg and 1.4 × 10⁵ CD34+ cells/kg. Cumulative incidence of neutrophil engraftment was 76% at day 60. Results: Of those who did not engraft, two patients remain alive following subsequent allogeneic bone marrow transplant. There were no deaths caused by graft‐versus‐host disease. Overall survival at median follow up of 28 months was 62%. Two year overall survival was influenced by type of disease (non‐malignant = 91 ± 9% vs malignant = 41 ± 13%, P= 0.005), total nucleated cell dose (>3.5 × 10⁷/kg = 87 ± 9% vs <3.5 × 10⁷/kg = 34 ± 15%, P= 0.01) and CD34 dose (>1.7 × 10⁵/kg = 92% vs <1.7 × 10⁵/kg = 46%, P= 0.04). Age and human leucocyte antigen match did not influence survival. Four relapses occurred, all of which were fatal. Conclusion: Cord blood transplantation for malignant and non‐malignant disease is practised in Western Australia and outcomes are satisfactory. Trends and techniques in cord blood transplantation in this state are comparable with those observed nationally and overseas. Although numbers are small, cell dose appears to be predictive of overall survival.     

A dilemma for doctors

Community physicians have recently, albeit often reluctantly, been involved in preparations for nuclear war. This paper suggests an alternative: that they should use their skills in epidemiology and in preventive and social medicine in the prevention of nuclear war.     

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy

1 Background and aims

Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long‐term outcomes of upgrading from pacemakers to CRT with (CRT‐D) or without (CRT‐P) defibrillation in patients with no history of sustained ventricular arrhythmias.

2 Methods and results

In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT‐P or CRT‐D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4–7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10–1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05–1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96–1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36–0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34–0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40–0.82) were lower after CRT‐D than after CRT‐P.

3 Conclusion

Upgrading from pacemakers to CRT was associated with a similar long‐term risk of mortality and morbidity to de novo CRT. After upgrade, CRT‐D was associated with a lower mortality than CRT‐P.     

Unintended effects of orphan product designation for rare neurological diseases

Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits, and perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs, both for newly developed drugs and for drugs that were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one‐fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington disease, adrenocorticotropic hormone for infantile spasms, and enzyme replacement therapy with alglucosidase alpha for Pompe disease, we highlight these paradoxical effects. ANN NEUROL 2012;72:481–490     

Global thinking,local action

This article examines the risk of proliferation of nuclear weapons to several Third World countries, exemplified by recent events in Iraq, and the possibility of rapid acquisition of a nuclear weapons capability in developed countries. It considers the role of the International Atomic Energy Agency and the United Nations in preventing proliferation and calls for wider powers for the latter. The role of the civil nuclear power industry and of reprocessing of nuclear fuel to produce plutonium is stressed, with emphasis on the part played by nuclear power in Japan and the THORP reprocessing plant at Sellafield.     

Case report and review of nonischemic spontaneous papillary muscle rupture reports between 2000 and 2015

Spontaneous papillary muscle rupture (PMR) is a rare cardiovascular emergency. We present a 63‐year‐old male who presents with acute dyspnea who was found to have an anterior PMR, with no evidence of coronary artery disease, infection, or trauma. A review of cases of nonischemic spontaneous PMR published in 2000–2015 identified 11 additional cases of spontaneous PMR. Posterior and anterior papillary muscles involvement was identified in 54.5% and 45.5% of cases, respectively. Rapid identification due to advances in imaging modalities and improved surgical management has led to optimal outcomes in patients with spontaneous PMR.     

Milestones in myoclonus

This review examines some of the advances in understanding myoclonus over the last 25 years. The classification of myoclonus into cortical, brainstem, and spinal forms has been consolidated, each with distinctive clinical characteristics and physiological mechanisms. New genetic causes of myoclonus have been identified, and the molecular basis of several of these conditions has been discovered. It is increasingly apparent that disease of the cerebellum is particularly important in the genesis of cortical reflex myoclonus. However, the precise mechanism and origin of myoclonus in many situations remain uncertain. Effective treatment of myoclonus remains limited, and the challenge lies ahead to develop more therapeutic options. © 2011 Movement Disorder Society