Written versus verbal consent: a qualitative study of stakeholder views of consent procedures used at the time of recruitment into a peripartum trial conducted in an emergency setting.

BACKGROUND: Obtaining prospective written consent from women to participate in trials when they are experiencing an obstetric emergency is challenging. Alternative consent pathways, such as gaining verbal consent at enrolment followed, later, by obtaining written consent, have been advocated by some clinicians and bioethicists but have received little empirical attention. We explored women's and staff views about the consent procedures used during the internal pilot of a trial (GOT-IT), where the protocol permitted staff to gain verbal consent at recruitment. METHODS: Interviews with staff (n = 27) and participating women (n = 22). Data were analysed thematically and interviews were cross-compared to identify differences and similarities in participants' views about the consent procedures used. RESULTS: Women and some staff highlighted benefits to obtaining verbal consent at trial enrolment, including expediting recruitment and reducing the burden on those left exhausted by their births. However, most staff with direct responsibility for taking consent expressed extreme reluctance to proceed with enrolment until they had obtained written consent, despite being comfortable using verbal procedures in their clinical practice. To account for this resistance, staff drew a strong distinction between research and clinical care and suggested that a higher level of consent was needed when recruiting into trials. In doing so, staff emphasised the need to engage women in reflexive decision-making and highlighted the role that completing the consent form could play in enabling and evidencing this process. While most staff cited their ethical responsibilities to women, they also voiced concerns that the absence of a signed consent form at recruitment could expose them to greater risk of litigation were an individual to experience a complication during the trial. Inexperience of recruiting into peripartum trials and limited availability of staff trained to take consent also reinforced preferences for obtaining written consent at recruitment. CONCLUSIONS: While alternative consent pathways have an important role to play in advancing emergency medicine research, and may be appreciated by potential recruits, they may give rise to unintended ethical and logistical challenges for staff. Staff would benefit from training and support to increase their confidence and willingness to recruit into trials using alternative consent pathways. TRIAL REGISTRATION: This qualitative research was undertaken as part of the GOT-IT Trial (trial registration number: ISCRTN 88609453 ). Date of registration 26/03/2014.

Vitamin C and the risk of acute myocardial infarction.

BACKGROUND: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. OBJECTIVE: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). DESIGN: Male patients (n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. RESULTS: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 micromol/L, respectively) was 8.37 (95% CI: 3.28, 21. 4) after adjustment for classic risk factors. At 3 mo, mean (+/-SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 +/- 1.2 to 35.1 +/- 1.9 micromol/L (P < 0. 001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. CONCLUSIONS: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response.

Gene-directed enzyme prodrug therapy for localized chemotherapeutics in allograft and xenograft tumor models.

Most chemotherapy regimens rely on systemic administration of drugs leading to a wide array of toxicities. Using viral-vector-mediated gene modification of muscle tissues, we have developed a method for gene-directed enzyme prodrug therapy that allows for localized drug administration. An inactive prodrug of geldanamycin was activated locally for inhibition of tumor growth without systemic toxicities. A recombinant adeno-associated virus (rAAV) was used to deliver ß-galactosidase (LacZ) to the treatment group and green fluorescent protein to the control group. After 1 week, both groups received adenocarcinoma cells in the same location as the previous rAAV injection. The geldanamycin prodrug was administered 1 h later via intraperitoneal injection. Tumor growth was significantly suppressed in animals whose muscles were gene modified to express ß-galactosidase compared with the control. Serum assay to access hepatotoxicity resulted in no significant differences between the animals treated with the inactive or activated form of geldanamycin, indicating minimal damage to non-target organs. Using gene-directed enzyme prodrug therapy, in combination with novel recombinant AAV vectors, we have developed a method for localized activation of chemotherapeutic agents that limits the toxicities seen with traditional systemic administration of these potent drugs.

Contemporary management of acute coronary syndromes: does the practice match the evidence? The global registry of acute coronary events (GRACE).

OBJECTIVE: To determine to what extent evidence based guidelines are followed in the management of acute coronary syndromes (ACS) in the UK, elsewhere in Europe, and multinationally, and what the outcomes are. DESIGN: Multinational, prospective, observational registry (GRACE, global registry of acute coronary events) with six months' follow up. SETTING: Patients presenting to a cluster of hospitals. The study was designed to collect data representative of the full spectrum of ACS in specific geographic populations. PATIENTS: Patients admitted with a working diagnosis of unstable angina or suspected myocardial infarction (MI). MAIN OUTCOME MEASURES: Death during hospitalisation and at six months' follow up (adjusted for baseline risks). RESULTS: In ST elevation MI, reperfusion was applied more often in the UK (71%) than in Europe (65%) and multinationally (59%) (p < 0.01). However, this was almost entirely by lytic treatment, in contrast with elsewhere (primary percutaneous coronary intervention 1%, 29%, 16%, respectively). Statins were applied more frequently in the UK for all classes of patients with ACS (p < 0.0001). In contrast there was lower use of revascularisation procedures in non-ST MI (20% v 37% v 28%, respectively) and glycoprotein IIb/IIIa antagonists (6% v 25% v 26%, respectively). In-hospital death rates, adjusted for baseline risk, were not significantly different but six month death rates were higher in the UK for ST elevation MI (7.2% UK, 4.3% Europe, 5.3% multinationally; p < 0.0001) and non-ST elevation MI (7.5%, 6.2%, and 6.7%, respectively; p = 0.012, UK v Europe). CONCLUSIONS: Current management of ACS in the UK more closely follows the recommendations of the National Service Framework than British or European guidelines. Differences in practice may account for the observed higher event rates in the UK after hospital discharge.

Cognitive functioning and symptomatology in chronic schizophrenia.

Chronic schizophrenic patients in a long stay hospital were found to have low levels of intelligence (mean IQ of 80), which was attributed to the effects of substantial intellectual deterioration on below average pre-morbid levels of functioning. Patients with the lowest IQ scores had the least severe positive symptoms but symptomatology was not related to age or extent of intellectual decline. Speed of functioning was relatively more impaired than level of intellectual functioning, with cognitive speed being more affected than motor speed. The severity of negative but not positive symptoms was significantly related to the severity of bradyphrenia (cognitive slowing), a result which would be consistent with the notion of a subcortical pathology in patients with Type II schizophrenia.