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Cahn P.,Fundacion Huesped | Pozniak A.L.,Chelsea and Westminster Hospital NHS Foundation Trust | Mingrone H.,Fundacion IDEAA | Brites C.,Federal University of Bahia | And 16 more authors.
The Lancet | Year: 2013

Background Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profile. We evaluated safety, efficacy, and emergent resistance in antiretroviral- experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance. Methods ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at ClinicalTrials.gov, NCT01231516. Findings Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference -3·7%, 95% CI -6·1 to -1·2; p=0·003). Adverse event frequencies were similar across groups; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea (71 [20%] vs 64 [18%] patients), upper respiratory tract infection (38 [11%] vs 29 [8%]), and headache (33 [9%] vs 31 [9%]). Safety events leading to discontinuation were infrequent in both groups (nine [3%] dolutegravir, 14 [4%] raltegravir). Interpretation Once-daily dolutegravir, in combination with up to two other antiretroviral drugs, is well tolerated with greater virological effect compared with twice-daily raltegravir in this treatment-experienced patient group. Funding ViiV Healthcare. © 2013 Elsevier Ltd. Source

Johnston M.J.,Imperial College London | King D.,Imperial College London | Arora S.,Imperial College London | Behar N.,Chelsea and Westminster Hospital NHS Foundation Trust | And 3 more authors.
American Journal of Surgery | Year: 2015

Background Outdated communication technologies in healthcare can place patient safety at risk. This study aimed to evaluate implementation of the WhatsApp messaging service within emergency surgical teams.Methods A prospective mixed-methods study was conducted in a London hospital. All emergency surgery team members (n = 40) used WhatsApp for communication for 19 weeks. The initiator and receiver of communication were compared for response times and communication types. Safety events were reported using direct quotations.Results More than 1,100 hours of communication pertaining to 636 patients were recorded, generating 1,495 communication events. The attending initiated the most instruction-giving communication, whereas interns asked the most clinical questions (P <.001). The resident was the speediest responder to communication compared to the intern and attending (P <.001). The participants felt that WhatsApp helped flatten the hierarchy within the team.Conclusions WhatsApp represents a safe, efficient communication technology. This study lays the foundations for quality improvement innovations delivered over smartphones. © 2015 Elsevier Inc. All rights reserved. Source

Falconer J.,Chelsea and Westminster Hospital NHS Foundation Trust
The journal of family health care | Year: 2010

Gastro-oesophageal reflux (GOR) is a norma physiological process occurring daily in healthy infants with similar frequency in both breast- and bottle-fed infants. It is generally considered uncomplicated and self-limiting, resolving spontaneously by 12-14 months of age. In contrast, gastro-oesophageal reflux disease (GORD) is associated with more severe symptoms and, on occasions, oesophagitis. In the small percentage of cases that do not respond to simple feeding measures, a trial for 2-4 weeks using an extensively hydrolysed formula may be considered. Thickeners and antiregurgitation feeds may help with the frequency of overt regurgitation. Feeding difficulties can be a problem in infants with reflux, with some suffering extreme aversion to texture. In the small percentage of infants who experience faltering growth, high-calorie formulae can be used. In those with severe feeding difficulties or severe faltering growth, tube feeding may be required. Infants should ideally be managed within a multidisciplinary team including a speech and language therapist, psychologist, dietitian and paediatrician. Source

Raffi F.,University of Nantes | Pozniak A.L.,Chelsea and Westminster Hospital NHS Foundation Trust | Wainberg M.A.,McGill University
Journal of Antimicrobial Chemotherapy | Year: 2014

Efavirenz has been recommended as a preferred third agent together with two nucleos(t)ides for first-line combination antiretroviral therapy (ART) for >15 years. The availability of efavirenz in a fixed-dose combination makes it very attractive. However, because of (i) adverse events associated with efavirenz, (ii) a poorer overall efficacy of efavirenz compared with newer antiretrovirals, (iii) the ranking of efavirenz as FDA Pregnancy Category D and (iv) the relatively high prevalence of transmitted drug-resistance mutations, there is a need to reconsider the role of efavirenz in first-line ART. We review the available evidence that challenges efavirenz's current position in first-line HIV treatment guidelines. Apart from its animal teratogenic potential, and moderate neuropsychiatric adverse events associated with its use, efavirenz has recently been associated with an increased risk of suicidality when compared with other antiretroviral drugs. Most importantly, efavirenz has demonstrated overall inferior efficacy to various comparator drugs, which include rilpivirine, raltegravir and dolutegravir, in antiretroviral-naive patients. Furthermore, epidemiological data indicate that the prevalence of non-nucleoside reverse transcriptase inhibitor resistance has reached 5%-8% in various parts of the world, and minority transmitted non-nucleoside reverse transcriptase inhibitor resistance-associated mutations can have a negative impact on the outcome of first-line efavirenz-based ART. Based on considerations of efficacy, toxicity and resistance, it is time to reconsider the routine use of efavirenz in ART. This, of course, presupposes that other antiretrovirals will be available in place of efavirenz, and may not be applicable in certain developing country settings where this is not the case. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Johnston M.,Center for Patient Safety | Arora S.,Center for Patient Safety | Anderson O.,Center for Patient Safety | King D.,Center for Patient Safety | And 4 more authors.
Annals of Surgery | Year: 2015

Objective: To systematically risk assess and analyze the escalation of care process in surgery so as to identify problems and provide recommendations for intervention. Background: The ability to escalate care appropriately when managing deteriorating patients is a hallmark of surgical competence and safe postoperative care. Healthcare-Failure-Mode-Effects-Analysis (HFMEA) is a methodology adapted from safety-critical industries, which allows for hazardous process failures to be prospectively identified and solutions to be recommended. Methods: Forty-two hours of ethnographic observations on surgical wards in 3 London hospitals (phase 1) formed the basis of an escalation process diagram. A risk-assessment survey identified failures associated with process steps and attributed hazard scores (phase 2). Patient safety and clinical risk experts validated hazard scores through a group consensus meeting (phase 3). Hazardous failures were taken forward to multidisciplinary HFMEA where cause analysis was applied and interventions were recommended (phase 4). Results: Observations identified 33 steps in the escalation process. The risk-assessment survey (30 surgical staff members, 100% response) and expert consensus group identified 18 hazardous failures associated with these steps. The HFMEA team identified 3 adequately controlled failures; therefore, 15 were subjected to cause analysis. Outdated communication technology, understaffing, and hierarchical barriers were identified as root causes of failure. Participants recommended interventions based on these findings including defined escalation protocols, human factors education, enhanced communication technology, and improved clinical supervision. Conclusions: Failures in the escalation process amenable to intervention were systematically identified. This mapping of the escalation process will allow tailored interventions to enhance surgical training and patient safety. © 2014 Wolters Kluwer Health, Inc. All rights reserved. Source

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