Report on a visit to CIFT, Cochin, India to provide training and guidance in studying microbiological problems in cultured fish/seafoods - 13 February - 11 March 1995

A visit was made to the Central Institute of Fisheries Technology (CIFT), Cochin as part of the ODA funded collaborative programme between NRI and CIFT. The aim of the work was to further strengthen the skills of CIFT staff and to help in institution building. Staff within the Microbiology, Fermentation and Biotechnology Section (MFB Section) were given training in the identification of selected microbial pathogens and guidance in undertaking research studies at CIFT into the microbiological problems likely to be encountered with the spread of aquaculture systems in India

A qualitative study of patients’ feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England : implications for service improvement

AbstractObjective Outpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients’ experiences of OPAT.Design In-depth, semistructured interviews.Setting Purposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or self-administration models.Participants We undertook 28 semistructured interviews and one focus group (n=4).Results Despite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information.Conclusion Services configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service.This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0

Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review

Objective: Evaluate evidence of the efficacy, safety, acceptability and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models. Design: A systematic review. Data sources: MEDLINE, EMBASE, CINAHL, Cochrane Library, National Health Service (NHS) Economic Evaluation Database (EED), Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA) Registry, Health Business Elite, Health Information Management Consortium (HMIC), Web of Science Proceedings, International Pharmaceutical Abstracts, British Society for Antimicrobial Chemotherapy website. Searches were undertaken from 1993 to 2015. Study selection: All studies, except case reports, considering adult patients or practitioners involved in the delivery of OPAT were included. Studies combining outcomes for adults and children or non-intravenous (IV) and IV antibiotic groups were excluded, as were those focused on process of delivery or clinical effectiveness of 1 antibiotic over another. Titles/abstracts were screened by 1 reviewer (20% verified). 2 authors independently screened studies for inclusion. Results: 128 studies involving >60 000 OPAT episodes were included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved a comparator (23%). There was little difference in duration of OPAT treatment compared with inpatient therapy, and overall OPAT appeared to produce superior cure/improvement rates. However, when models were considered individually, outpatient delivery appeared to be less effective, and self-administration and specialist nurse delivery more effective. Drug side effects, deaths and hospital readmissions were similar to those for inpatient treatment, but there were more line-related complications. Patient satisfaction was high, with advantages seen in being able to resume daily activities and having greater freedom and control. However, most professionals perceived challenges in providing OPAT. Conclusions: There were no systematic differences related to the impact of OPAT on treatment duration or adverse events. However, evidence of its clinical benefit compared with traditional inpatient treatment is lacking, primarily due to the dearth of good quality comparative studies. There was high patient satisfaction with OPAT use but the few studies considering practitioner acceptability highlighted organisational and logistic barriers to its delivery

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

Introduction Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. Methods and analysis The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive either laparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. Ethics and dissemination The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The results from the trial will be presented at national and international colorectal conferences and will be submitted for publication to peer-reviewed journals. Trial registration number ISRCTN15681041; Pre-results

A TRAIL-R1-specific ligand in combination with doxorubicin selectively targets primary breast tumour cells for apoptosis

A TRAIL-R1-specific ligand in combination with doxorubicin selectively targets primary breast tumour cells for apoptosi

Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998–2000) and BR3 (2003–05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant )Fundação de Amparo à Pesquisa do Estado de São PauloFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG grant

Measuring patient-perceived continuity of care for patients with long-term conditions in primary care

Background: Continuity of care is widely acknowledged as important for patients with multi-morbidity but simple, service-orientated indices cannot capture the full impact of continuity in complex care delivery systems. The patient's perspective is important to assess outcomes fully and this is challenging because generic measures of patient-perceived continuity are lacking. We investigate the Chao Perception of Continuity (Chao PC) scale to determine its suitability as a measure of continuity of care for patients with a long-term condition (stroke), and co-morbidity, in a primary care setting. Methods: Design and Setting: A questionnaire study embedded in a prospective observational cohort study of outcomes for patients following acute stroke. Participants: 168 community dwelling patients (58% male) mean age 68 years a minimum one year post-stroke. Functional status: Barthel Index mean =16. Intervention: A 23-item questionnaire, the Chao Perception of Continuity (Chao PC) scale, sent by post to their place of residence or administered face to face as part of the final cohort study assessment. Results: 310 patients were invited to participate; 168 (54%) completed a questionnaire. All 23 questionnaire items were entered into a Principal Component Analysis. Emergent factors from the exploratory analysis were (1) inter-personal trust (relational continuity); (2) interpersonal knowledge and information (informational and relational continuity) and (3) the process of care (managerial continuity). The strongest of these was inter-personal trust. Conclusion: The context-specific items in the Chao PC scale are difficult for respondents to interpret in a United Kingdom Primary Care setting resulting in missing data and low response rates. The Chao-PC therefore cannot be recommended for wider application as a general measure of continuity of care without significant modification. Our findings reflect the acknowledged dimensions of continuity and support the concept of continuity of care as a multi-dimensional construct. We demonstrate the overlapping boundaries across the dimensions in the factor structure derived. Trust and interpersonal knowledge are clearly identified as valuable components of any patient-perceived measure of continuity of care

Alteration of AKT Activity Increases Chemotherapeutic Drug and Hormonal Resistance in Breast Cancer yet Confers an Achilles Heel by Sensitization to Targeted Therapy

The PI3K/PTEN/Akt/mTOR pathway plays critical roles in the regulation of cell growth. The effects of this pathway on drug resistance and cellular senescence of breast cancer cells has been a focus of our laboratory. Introduction of activated Akt or mutant PTEN constructs which lack lipid phosphatase [PTEN(G129E)] or lipid and protein phosphatase [PTEN(C124S)] activity increased the resistance of the cells to the chemotherapeutic drug doxorubicin, and the hormonal drug tamoxifen. Activated Akt and PTEN genes also inhibited the induction of senescence after doxorubicin treatment; a phenomenon associated with unrestrained proliferation and tumorigenesis. Interference with the lipid phosphatase domain of PTEN was sufficient to activate Akt/mTOR/p70S6K as MCF-7 cells transfected with the mutant PTEN gene lacking the lipid phosphatase activity [PTEN(G129E)] displayed elevated levels of activated Akt and p70S6K compared to empty vector transfected cells. Cells transfected with mutant PTEN or Akt constructs were hypersensitive to mTOR inhibitors when compared with the parental or empty vector transfected cells. Akt-transfected cells were cultured for over two months in tamoxifen from which tamoxifen and doxorubicin resistant cells were isolated that were >10-fold more resistant to tamoxifen and doxorubicin than the original Akt-transfected cells. These cells had a decreased induction of both activated p53 and total p21Cip1 upon doxorubicin treatment. Furthermore, these cells had an increased inactivation of GSK-3β and decreased expression of the estrogen receptor-α. In these drug resistant cells, there was an increased activation of ERK which is associated with proliferation. These drug resistant cells were hypersensitive to mTOR inhibitors and also sensitive to MEK inhibitors, indicating that the enhanced p70S6K and ERK expression was relevant to their drug and hormonal resistance. Given that Akt is overexpressed in greater than 50% of breast cancers, our results point to potential therapeutic targets, mTOR and MEK. These studies indicate that activation of the Akt kinase or disruption of the normal activity of the PTEN phosphatase can have dramatic effects on activity of p70S6K and other downstream substrates and thereby altering the therapeutic sensitivity of breast cancer cells. The effects of doxorubicin and tamoxifen on induction of the Raf/MEK/ERK and PI3K/Akt survival pathways were examined in unmodified MCF-7 breast cells. Doxorubicin was a potent inducer of activated ERK and to a lesser extent Akt. Tamoxifen also induced ERK. Thus a consequence of doxorubicin and tamoxifen therapy of breast cancer is the induction of a pro-survival pathway which may contribute to the development of drug resistance. Unmodified MCF-7 cells were also sensitive to MEK and mTOR inhibitors which synergized with both tamoxifen and doxorubicin to induce death. In summary, our results point to the key interactions between the PI3K/PTEN/Akt/mTOR and Raf/ MEK/ERK pathways in regulating chemotherapeutic drug resistance/sensitivity in breast cancer and indicate that targeting these pathways may prevent drug and hormonal resistance. Orignally published Advances in Enzyme Regulation, Vol. 48, No. 1, 2008

Developing a surgical trial intervention protocol: using qualitative methods in the operating theatre

Introduction Surgery is a complex intervention, so it is important to establish standards for both the standard and ‘novel’ procedures in randomized controlled trials (RCTs) that demonstrate that interventions are delivered as intended to fully understand and explain trial results. This study set out to identify and agree the key steps of a surgical intervention to be tested in the ‘near infrared fluorescent imaging in thyroid surgery’ (NIFTy) RCT to inform development of the surgical protocol, and trial materials. Method Qualitative case studies of surgeries were undertaken prior to undertaking an RCT to evaluate the potential of a device to reduce post-surgical hypoparathyroidism. Each case study involved non-participant observation, video capture of total and completion thyroidectomies, and interviews with surgeons. A typology of operative steps was constructed. Two surveys were undertaken (1) to identify current practice around parathyroid identification; and (2) to determine surgeon views on the surgical steps. An international expert panel of six clinicians met to review findings and agree on the surgical steps (mandatory/optional) for operations in the RCT, including timing for use of fluorescence and the data items to be collected. Results Ten case studies were undertaken. Video, observation and interview data found differences in surgical approach were driven only by pathology. A typology detailing the surgical steps and points where imaging could be used was developed. Sixty-four surgeons responded to survey 1; three-quarters always looked for parathyroid glands when operating. Forty surgeons responded to survey 2; capsular dissection of the thyroid lobe, preservation of parathyroid pedicle, and clinical assessment were important for parathyroid preservation. The expert panel agreed the key surgical components. These informed key data collection in NIFTy. Two specific surgical steps were strongly recommended and three mandated. Conclusion Qualitative research in the operating theatre, prior to RCT allowed the identification of key components of the surgical intervention. The surveys and expert panel provided certainty about the acceptability of the surgical protocol and identified the core data to collect to evidence surgical decision making prior to embarking on the RCT. This qualitative process achieved clinical buy-in, improved trial conduct and allowed full explanation of the subsequent trial results. Trial registration ISRCTN59074092. Registration date: 07/03/2022