Acquired heart block: A possible complication of patent ductus arteriosus in a preterm infant

A large patent ductus arteriosus (PDA) is a frequently encountered clinical problem in extremely low birth weight (ELBW) infants. It leads to an increased pulmonary blood flow and in a decreased or reversed diastolic flow in the systemic circulation, resulting in complications. Here we report a possible complication of PDA not previously published. On day 8 of life, a male ELBW infant (birth weight 650 g) born at a gestational age of 23 weeks and 3 days developed an atrioventricular block (AV block). The heart rate dropped from 168/min to 90/min, and the ECG showed a Wenckebach second-degree AV block and intraventricular conduction disturbances. Echocardiography demonstrated a PDA with a large left-to-right shunt and large left atrium and left ventricle with high contractility. Within several minutes after surgical closure of the PDA, the heart rate increased, and after 30 min the AV block had improved to a 1: 1 conduction ratio. Echocardiography after 2 h revealed a significant decrease of the left ventricular and atrial dimensions. Within 12 h, the AV block completely reversed together with the intraventricular conduction disturbances. We suggest that PDA with a large left-to-right shunt and left ventricular volume overload may lead to an AV block in an ELBW infant. Surgical closure of the PDA may be indicated. Copyright (C) 2007 S. Karger AG, Basel

Estimating the causal effects of modifiable, non-genetic factors on Huntington disease progression using propensity score weighting

INTRODUCTION: Despite being genetically inherited, it is unclear how non-genetic factors (e.g., substance use, employment) might contribute to the progression and severity of Huntington's disease (HD). METHODS: We used propensity score (PS) weighting in a large (n = 2914) longitudinal dataset (Enroll-HD) to examine the impact of education, employment status, and use of tobacco, alcohol, and recreational and therapeutic drugs on HD progression. Each factor was investigated in isolation while controlling for 19 other factors to ensure that groups were balanced at baseline on potential confounders using PS weights. Outcomes were compared several years later using doubly robust models. RESULTS: Our results highlighted cases where modifiable (non-genetic) factors - namely light and moderate alcohol use and employment - would have been associated with HD progression in models that did not use PS weights to control for baseline imbalances. These associations did not hold once we applied PS weights to balance baseline groups. We also found potential evidence of a protective effect of substance use (primarily marijuana use), and that those who needed antidepressant treatment were likely to progress faster than non-users. CONCLUSIONS: Our study is the first to examine the effect of non-genetic factors on HD using a novel application of PS weighting. We show that previously-reported associated factors - including light and moderate alcohol use - are reduced and no longer significantly linked to HD progression after PS weighting. This indicates the potential value of PS weighting in examining non-genetic factors contributing to HD as well as in addressing the known biases that occur with observational data

How a turn to critical race theory can contribute to our understanding of 'race', racism and anti-racism in sport

As long as racism has been associated with sport there have been consistent, if not coordinated or coherent, struggles to confront its various forms. Critical race theory (CRT) is a framework established to challenge these racialized inequalities and racism in society and has some utility for anti-racism in sport. CRT's focus on social justice and transformation are two areas of convergence between critical race theorists and anti-racists. Of the many nuanced and pernicious forms of racism, one of the most obvious and commonly reported forms of racism in sport, racial abuse, has been described as a kind of dehumanizing process by Gardiner (2003), as those who are its target are simultaneously (re)constructed and objectified according to everyday myth and fantasy. However, this is one of the many forms of everyday racist experiences. Various forms of racism can be experienced in boardrooms, on television, in print, in the stands, on the sidelines and on the pitch. Many times racism is trivialized and put down as part of the game (Long et al., 2000), yet its impact is rarely the source of further exploration. This article will explore the conceptualization of 'race' and racism for a more effective anti-racism. Critical race theory will also be used to explore the ideas that underpin considerations of the severity of racist behaviour and the implications for anti-racism. © The Author(s) 2010

Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

A new concept for the combination of optical interferometers and high-resolution spectrographs

The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia

<p>Abstract</p> <p>Background</p> <p>Primary eosinophlia associated with the <it>FIP1L1-PDGFRA </it>rearrangement represents a subset of chronic eosinophilic leukaemia (CEL) and affected patients are very sensitive to imatinib treatment. This study was undertaken in order to examine the prevalence and the associated clinicopathologic and genetic features of <it>FIP1L1-PDGFRA </it>rearrangement in a cohort of 15 adult patients presenting with profound eosinophilia (> 1.5 × 10⁹/L).</p> <p>Methods</p> <p>Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of <it>FIP1L1-PDGFRA </it>rearrangement and the results confirmed by direct sequencing. <it>C-KIT</it>-D816V mutation was analysed retrospectively by PCR and restriction-fragment-length-polymorphism (PCR-RFLP), in all cases with primary eosinophilia.</p> <p>Results</p> <p>Two male patients with splenomegaly carried the <it>FIP1L1-PDGFRA </it>rearrangement, whilst 2 others were ultimately classified as suffering from idiopathic hypereosinophlic syndrome (HES) and one from systemic mastocytosis. These patients were negative for the <it>C-KIT</it>-D816V mutation and received imatinib (100–400 mg daily). Patients with CEL and HES responded to imatinib and remained in complete haematological, clinical and molecular (for carriers of <it>FIP1L1-PDGFRA </it>rearrangement) remission for a median of 28.2 months (range: 11–54), whilst the patient with systemic mastocytosis did not respond. Interestingly, in both patients with <it>FIP1L1-PDGFRA </it>rearrangement, the breakpoints into <it>PDGFRA </it>were located within exon 12 and fused with exons 8 and 8a of <it>FIP1L1</it>, respectively.</p> <p>Conclusion</p> <p>An early diagnosis of <it>FIPIL1-PDGFRA</it>-positive CEL and imatinib treatment offer to the affected patients an excellent clinical therapeutic result, avoiding undesirable morbidity. Moreover, although the molecular mechanisms underlying disease pathogenesis remain to be determined, imatinib can be effective in patients with idiopathic HES.</p