Description and process evaluation of pharmacists’ interventions in a pharmacist-led information technology-enabled multicentre cluster randomised controlled trial for reducing medication errors in general practice (PINCER trial)

Objective To undertake a process evaluation of pharmacists' recommendations arising in the context of a complex IT-enabled pharmacist-delivered randomised controlled trial (PINCER trial) to reduce the risk of hazardous medicines management in general practices. Methods PINCER pharmacists manually recorded patients’ demographics, details of interventions recommended, actions undertaken by practice staff and time taken to manage individual cases of hazardous medicines management. Data were coded and double entered into SPSS v15, and then summarised using percentages for categorical data (with 95% CI) and, as appropriate, means (SD) or medians (IQR) for continuous data. Key findings Pharmacists spent a median of 20 minutes (IQR 10, 30) reviewing medical records, recommending interventions and completing actions in each case of hazardous medicines management. Pharmacists judged 72% (95%CI 70, 74) (1463/2026) of cases of hazardous medicines management to be clinically relevant. Pharmacists recommended 2105 interventions in 74% (95%CI 73, 76) (1516/2038) of cases and 1685 actions were taken in 61% (95%CI 59, 63) (1246/2038) of cases; 66% (95%CI 64, 68) (1383/2105) of interventions recommended by pharmacists were completed and 5% (95%CI 4, 6) (104/2105) of recommendations were accepted by general practitioners (GPs), but not completed at the end of the pharmacists’ placement; the remaining recommendations were rejected or considered not relevant by GPs. Conclusions The outcome measures were used to target pharmacist activity in general practice towards patients at risk from hazardous medicines management. Recommendations from trained PINCER pharmacists were found to be broadly acceptable to GPs and led to ameliorative action in the majority of cases. It seems likely that the approach used by the PINCER pharmacists could be employed by other practice pharmacists following appropriate training

Multimodality Imaging in the Evaluation of Cardiovascular Manifestations of Malignancy

Up to one third of the population will die as a direct result of cancer. Accurate and timely diagnosis of disease often requires multiple different approaches including the use of modern imaging techniques. Prompt recognition of adverse consequences of some anti-cancer therapies also requires a knowledge of the optimum imaging strategy for the problem at hand. The purpose of this article is to review not only some of the commoner cardiovascular manifestations of malignancy but also to discuss the strengths, weaknesses and appropriate use of cardiovascular imaging modalities

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

ObjectivesThe objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy.BackgroundPregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy.MethodsThis was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks).ResultsSeventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy.ConclusionsMany pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy

Cardiac magnetic resonance imaging characteristics and pregnancy outcomes in women with Mustard palliation for complete transposition of the great arteries

AbstractBackgroundWomen with transposition of the great arteries (TGA) following atrial redirection surgery are at risk of pregnancy-associated arrhythmia and heart failure. The cardiovascular magnetic resonance imaging (CMR) characteristics of these women and the relationship of CMR findings to pregnancy outcomes have not been described.MethodsWe included 17 women with atrial redirection surgery and CMR within 2years of delivery.ResultsAll women were asymptomatic at baseline (New York Heart Association Class 1). CMR studies were completed pre-pregnancy in 3, antepartum/peripartum in 2, and postpartum in 12 women. Three women (3/17, 18%) experienced major cardiovascular events related to pregnancy: cardiac arrest (n=1) and symptomatic atrial arrhythmia (n=2). Median gestational age at delivery was 38weeks (24–39weeks) and birth weight was 2770g (2195–3720g). Complications were seen in 3 offspring (3/17, 18%): death (n=1) and prematurity (n=2). CMR characteristics included median right ventricular end diastolic volume 119mL/m2 (range 85–214mL/m2) and median right ventricular ejection fraction (RVEF) 37% (range 30–51%). All women with cardiovascular complications had an RVEF <35% (range 32–34%). The association between RVEF <35% and cardiovascular complications trended towards statistical significance (p=0.05). No statistically significant differences in CMR measurements were found between those with and without neonatal complications.ConclusionsWhile the majority of women in this cohort had successful outcomes following pregnancy, important cardiovascular complications were seen in a significant minority, all of whom had an RVEF <35%. The preliminary findings of our study provide impetus for a larger prospective study to evaluate the prognostic role of CMR in pregnant women with atrial redirection surgery

Maternal cardiac output and fetal doppler predict adverse neonatal outcomes in pregnant women with heart disease

Background-The mechanistic basis of the proposed relationship between maternal cardiac output and neonatal complications in pregnant women with heart disease has not been well elucidated. Methods and Results-Pregnant women with cardiac disease and healthy pregnant women (controls) were prospectively followed with maternal echocardiography and obstetrical ultrasound scans at baseline, third trimester, and postpartum. Fetal/neonatal complications (death, small-for-gestational-age or low birthweight, prematurity, respiratory distress syndrome, or intraventricular hemorrhage) comprised the primary study outcome. One hundred and twenty-seven women with cardiac disease and 45 healthy controls were enrolled. Neonatal events occurred in 28 pregnancies and were more frequent in the heart disease group as compared with controls (n=26/127 or 21% versus n=2/45 or 4%; P=0.01). Multiple complications in an infant were counted as a single outcome event. Neonatal complications in the heart disease group were small-for-gestational-age/low birthweight (n=18), prematurity (n=14), and intraventricular hemorrhage/respiratory distress syndrome (n=5). Preexisting obstetric risk factors (P=0.003), maternal cardiac output decline from baseline to third trimester (P=0.017), and third trimester umbilical artery Doppler abnormalities (P \u3c 0.001) independently predicted neonatal complications and were incorporated into a novel risk index in which 0, 1, and \u3e 1 predictor corresponded to expected complication rates of 5%, 30%, and 76%, respectively. Conclusions-Decline in maternal cardiac output during pregnancy and abnormal umbilical artery Doppler flows independently predict neonatal complications. These findings will enhance the identification of higher risk pregnancies that would benefit from close antenatal surveillance

Cardiac outcomes after pregnancy in women with congenital heart disease

Objective: Women with congenital heart disease (CHD) are at risk for adverse cardiac events during pregnancy; however, the risk of events late after pregnancy (late cardiac events; LCE) has not been well studied. A study was undertaken to examine the frequency and determinants of LCE in a large cohort of women with CHD. Design: Baseline characteristics and pregnancy were prospectively recorded. LCE (\u3e6 months after delivery) were determined by chart review. Survival analysis was used to determine the risk factors for LCE. Setting: A tertiary care referral hospital. Patients: The outcomes of 405 pregnancies were studied (318 women; median follow-up 2.6 years). Main outcome measures: LCE included cardiac death/ arrest, pulmonary oedema, arrhythmia or stroke. Results: LCE occurred after 12% (50/405) of pregnancies. The 5-year rate of LCE was higher in women with adverse cardiac events during pregnancy than in those without (27±9% vs 15±3%, HR 2.2, p=0.02). Women at highest risk for LCE were those with functional limitations/cyanosis (HR 3.9, 95% CI 1.2 to 13.0), subaortic ventricular dysfunction (HR 3.0, 95% CI 1.4 to 6.6), subpulmonary ventricular dysfunction and/or significant pulmonary regurgitation (HR 3.2, 95% CI 1.6 to 6.6), left heart obstruction (HR 2.6, 95% CI 1.2 to 5.2) and cardiac events before or during pregnancy (HR 2.6, 95% CI 1.3 to 4.9). In women with 0, 1 or \u3e1 risk predictors the 5-year rate of LCE was 762%, 2365% and 44610%, respectively (p\u3c0.001). Conclusions: In women with CHD, pre-pregnancy maternal characteristics can help to identify women at increased risk for LCE. Adverse cardiac events during pregnancy are important and are associated with an increased risk of LCE

Promotion of access to essential medicines for Non-Communicable Diseases: Practical implications of the UN Political Declaration

Access to medicines and vaccines to prevent and treat non-communicable diseases (NCDs) is unacceptably low worldwide. In the 2011 UN political declaration on the prevention and control of NCDs, heads of government made several commitments related to access to essential medicines, technologies, and vaccines for such diseases. 30 years of experience with policies for essential medicines and 10 years of scaling up of HIV treatment have provided the knowledge needed to address barriers to long-term effective treatment and prevention of NCDs. More medicines can be acquired within existing budgets with efficient selection, procurement, and use of generic medicines. Furthermore, low-income and middle-income countries need to increase mobilisation of domestic resources to cater for the many patients with NCDs who do not have access to treatment. Existing initiatives for HIV treatment offer useful lessons that can enhance access to pharmaceutical management of NCDs and improve adherence to long-term treatment of chronic illness; policy makers should also address unacceptable inequities in access to controlled opioid analgesics. In addition to off-patent medicines, governments can promote access to new and future on-patent medicinal products through coherent and equitable health and trade policies, particularly those for intellectual property. Frequent conflicts of interest need to be identified and managed, and indicators and targets for access to NCD medicines should be used to monitor progress. Only with these approaches can a difference be made to the lives of hundreds of millions of current and future patients with NCDs

On Non-Linear Actions for Massive Gravity

In this work we present a systematic construction of the potentially ghost-free non-linear massive gravity actions. The most general action can be regarded as a 2-parameter deformation of a minimal massive action. Further extensions vanish in 4 dimensions. The general mass term is constructed in terms of a "deformed" determinant from which this property can clearly be seen. In addition, our formulation identifies non-dynamical terms that appear in previous constructions and which do not contribute to the equations of motion. We elaborate on the formal structure of these theories as well as some of their implications.Comment: v3: 22 pages, minor comments added, version to appear in JHE

Conventional and sutureless techniques for management of the pulmonary veins: Evolution of indications from postrepair pulmonary vein stenosis to primary pulmonary vein anomalies

ObjectiveWe have previously reported a limited but favorable experience with a novel sutureless technique for surgical management of postoperative pulmonary vein stenosis occurring after repair of total anomalous pulmonary venous drainage. Because this technique requires integrity of the retrocardiac space for hemostasis, extension of the technique to the primary repair of pulmonary vein anomalies requires evaluation. This analysis reviews our experience with the sutureless technique in patients with postrepair pulmonary vein stenosis, as well as our extension of the technique into primary repair of pulmonary vein anomalies.MethodsRetrospective univariable-multivariable analysis of all pulmonary vein stenosis procedures and sutureless pulmonary vein procedures over a 20-year period was performed. Cox proportional hazards modeling was used to identify variables associated with freedom from reoperation or death.ResultsSixty patients underwent 73 procedures, with pulmonary vein stenosis present in 65 procedures. The sutureless technique was used in 40 procedures. Freedom from reoperation or death at 5 years after the initial procedure was 49%. Unadjusted freedom from reoperation or death was greater with the sutureless technique for patients with postrepair pulmonary vein stenosis (P = .04). By using multivariable analysis, a higher pulmonary vein stenosis score was associated with greater risk of reoperation or death. After adjustment, the sutureless repair was associated with a nonsignificant trend toward greater freedom from reoperation or death (P = .12). Despite the absence of retrocardiac adhesions, operative mortality was not increased with the sutureless technique (P = .64). Techniques to control bleeding (intrapleural hilar reapproximation) and improve exposure (inferior vena cava division) were identified.ConclusionThe sutureless technique for postrepair pulmonary vein stenosis is associated with encouraging midterm results. Extension of the indications for the technique to primary repair appears safe with the development of simple intraoperative maneuvers