Percutaneous Closure of Persistent Atrial Septal Defects After Pulmonary Vein Isolation

Pulmonary vein isolation (PVI) with radiofrequency or cryoballoon ablation to treat atrial fibrillation requires trans-septal puncture. This creates a small iatrogenic atrial septal defect (iASD). In most patients, the defect spontaneously closes after 3–6 months. However, persistent iASDs can cause hemodynamic changes and adverse consequences from inter-atrial shunting. Persistent post PVI iASDs that are clinically significant can be closed percutaneously. This diagnosis should be considered in patients with worsening dyspnea or fatigue after PVI. We present a case of post PVI iASDs causing immediate or late onset hemodynamic changes and clinical symptoms, which improved after ASD closure. We provide a review of previously reported cases and literature on post PVI ASD prevalence, risk factors and outcomes after ASD closure.     

Open repair of the acutely torn Achilles tendon under local anaesthetic

Background: Where surgery has been preferred, the torn Achilles tendon (AT) has most commonly been repaired under general or spinal anaesthetic (GA). Repair using local anaesthetic (LA) has been reported, but does not appear to be widely used. Methods: We retrospectively reviewed 87 patients, following open repair using either GA or LA at Nelson Hospital, 2001–2005. Calf strength and ankle range of motion (ROM) were assessed. Subjective pain and function were assessed using the American Academy of Orthopaedic Surgeons Foot and Ankle Questionnaire. Complications, time off work and sport, time in theatre, and hospital were recorded. Results: Fifty‐nine tendons were repaired under GA (68%) and 28 under LA (32%). Outcomes were similar for each group. There was no significant difference in strength and ROM. Foot and Ankle Questionnaire scores were similar. Total theatre time averaged 57 min for GA and 37 min for LA (P = 0.01). LA repairs (82%) were performed as a day case compared with 10% of the GA repairs (P = 0.01). LA patients had a quicker return to work. GA complications included two deep vein thromboses and two pulmonary emboli. One patient from each group had a re‐rupture. Conclusion: A repair of the acutely ruptured AT under LA is at least as effective as repair under GA with regard to function, long‐term pain and patient satisfaction. LA repair results in significant cost savings due to less theatre time, fewer anaesthetic costs, and a shorter hospital stay.     

Rationale, design and methods for a randomised and controlled trial to evaluate "Animal Fun" - a program designed to enhance physical and mental health in young children

Background

Preterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury. Inhaled Nitric Oxide, an effective therapy for pulmonary hypertension and hypoxic respiratory failure in the full term infant, has also been studied in preterm infants. The most recent Cochrane review of preterm infants includes 11 studies and 3,370 participants. The results show a statistically significant reduction in the combined outcome of death or chronic lung disease (CLD) in two studies with routine use of iNO in intubated preterm infants. However, uncertainty remains as a larger study (Kinsella 2006) showed no significant benefit for iNO for this combined outcome. Also, trials that included very ill infants do not demonstrate significant benefit. One trial of iNO treatment at a later postnatal age reported a decrease in the incidence of CLD. The aim of this individual patient meta-analysis is to confirm or refute these potentially conflicting results and to determine the extent to which patient or treatment characteristics may explain the results and/or may predict benefit from inhaled Nitric Oxide in preterm infants.

Methods/Design

The Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification.

Discussion

Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic review. To date 11 trials (n = 3298, 92% of available patients) have agreed to participate. Funding was successfully granted from Ikaria Inc as an unrestricted grant. A collaborative group was formed in 2006 with data collection commencing in 2007. It is anticipated that data analysis will commence in late 2009 with results being publicly available in 2010.     

Genetics of Dothistromin Biosynthesis in the Peanut Pathogen Passalora arachidicola

The peanut leaf spot pathogen Passalora arachidicola (Mycosphaerella arachidis) is known to produce dothistromin, a mycotoxin related to aflatoxin. This is a feature shared with the pine needle pathogen Dothistroma septosporum (Mycosphaerella pini). Dothistromin biosynthesis in D. septosporum commences at an unusually early stage of growth in culture compared to most other fungal secondary metabolites, and the biosynthetic genes are arranged in fragmented groups, in contrast to aflatoxin gene clusters. Dothistromin biosynthetic genes were identified and studied in P. arachidicola to determine if the attributes described in D. septosporum are shared by another dothistromin-producing species within the Class Dothideomycetes. It was shown that dothistromin biosynthesis is very similar in the two species with regard to gene sequence and gene synteny. Functional complementation of D. septosporum mutants with P. arachidicola dothistromin genes was also possible. These similarities support a vertical mode of dothistromin gene transmission. P. arachidicola also produced dothistromin at an early growth stage in culture, suggesting that this type of regulation pattern may be relevant to the biological role of dothistromin.     

Inhaled nitrous oxide during painful procedures: a satisfaction survey

Children with cystic fibrosis (CF) undergo repeated invasive medical procedures. This article summarises a survey of the use of nitrous oxide to minimise the psychological trauma and pain that was undertaken within the paediatric unit of a district general hospital (Williams et al 2004). Pain levels pre and post procedure, whether the treatment was effective, any adverse effects and comments by children and carers were recorded. Nitrous oxide was safe and effective in reducing pain, trauma and 'needle phobia'. It is now being offered to other children in the management of procedural pain.     

Culling and cattle controls influence tuberculosis risk for badgers

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.     

A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients

BACKGROUND/AIMS: ISIS 14803 is a 20-unit antisense phosphorothioate oligodeoxynucleotide that binds to hepatitis C virus (HCV) RNA at the translation initiation region of the internal ribosome entry site (IRES) and inhibits protein expression in cell culture and mouse models. This Phase I, open-label, dose-escalation trial of ISIS 14803 was performed in chronic HCV patients. METHODS: At least 7 days after receiving an initial single dose, twenty-eight patients received 0.5-3 mg/kg ISIS 14803 thrice weekly for 4 weeks by intravenous infusion or subcutaneous injection. RESULTS: In most patients, the 4-week treatment did not reduce plasma HCV RNA. However, 3 patients receiving > or =2 mg/kg had transient HCV reductions of 1.2-1.7 log(10) that persisted < or =32 days. These reductions were accompanied by asymptomatic, self-resolving elevations in serum alanine transaminase (ALT) levels to >10x the upper limit of normal. Two other patients had ALT flares without plasma HCV reduction. No clinical signs, symptoms of hepatic dysfunction, or laboratory changes in albumin or prothrombin time accompanied ALT elevations. CONCLUSIONS: ISIS 14803 treatment was associated with HCV reductions in only 3/28 patients. ALT flares in 5 patients also occurred. Further studies to evaluate ISIS 14803 treatment and the mechanisms of the ALT flares are now required.