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Purpose: PARP inhibitors synergize with topoisomerase inhibitors, and veliparib plus modified (m) FOLFIRI (no 5-FU bolus) had preliminary activity in metastatic pancreatic cancers. This study evaluated the safety and efficacy of second-line treatment with veliparib and mFOLFIRI versus FOLFIRI (control) for metastatic pancreatic cancer. Patients and Methods: This randomized phase II clinical trial led by the SWOG Cancer Research Network enrolled patients between September 1, 2016 and December 13, 2017. The median follow-up was 9 months (IQR 1–27). BRCA1/2 and homologous recombination DNA damage repair (HR-DDR) genetic defects were tested in blood and tumor biopsies. Patients received veliparib 200 mg twice daily, days 1–7 with mFOLFIRI days 3–5, or FOLFIRI in 14-day cycles. Results: After 123 of planned 143 patients were accrued, an interim futility analysis indicated that the veliparib arm was unlikely to be superior to control, and the study was halted. Median overall survival (OS) was 5.4 versus 6.5 months (HR, 1.23; P = 0.28), and median progression-free survival (PFS) was 2.1 versus 2.9 months (HR, 1.39; P = 0.09) with veliparib versus control. Grade 3/4 toxicities were more common with veliparib (69% vs. 58%, P = 0.23). For cancers with HR-DDR defects versus wild-type, median PFS and OS were 7.3 versus 2.5 months (P = 0.05) and 10.1 versus 5.9 months (P = 0.17), respectively, with FOLFIRI, and 2.0 versus 2.1 months (P = 0.62) and 7.4 versus 5.1 months (P = 0.10), respectively, with veliparib plus mFOLFIRI. Conclusions: Veliparib plus mFOLFIRI did not improve survival for metastatic pancreatic cancer. FOLFIRI should be further studied in pancreatic cancers with HR-DDR defects.

Objective The optimal neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDA) and the impact on surgical outcomes remains unclear. Methods S1505 (NCT02562716) was a randomized phase II study of perioperative chemotherapy with mFOLFIRINOX (Arm 1) or gemcitabine/nab-paclitaxel (Arm 2). Measured parameters included resection rate, margin positivity, pathologic response, and toxicity. Results Between 2015 and 2018, 147 patients were randomized. Of these, 44 (30%) were deemed ineligible (43 by central review). Of the 103 eligible patients, 77 (76%) completed preoperative therapy and underwent surgery; reasons patients did not undergo surgery included toxicity related to preoperative therapy (n = 9), progression (n = 9), or other (n = 7). Of the 77, 73 (95%) underwent successful resection; 21 (29%) required vascular reconstruction, 62 (85%) had negative (R0) margins, and 24 (33%) had a complete or major pathologic response to therapy. The grade 3-5 postoperative complication rate was 16%. Of the 73 patients completing surgery, 57 (78%) started and 46 (63%) completed postoperative therapy. This study represents the first prospective trial evaluating modern systemic therapy delivered in a neoadjuvant/perioperative format for resectable PDA. Conclusions We have demonstrated: (1) Based on the high percentage of enrolled, but ineligible patients, it is clear that adherence to strict definitions of resectable PDA is challenging; (2) Patients can tolerate modern systemic therapy and undergo successful surgical resection without prohibitive perioperative complications; (3) Completion of adjuvant therapy in the perioperative format is difficult; (4) Major pathologic response rate of 33% is encouraging.

The aim of this study was to assess the seroprevalence against serotype O FMD (foot and mouth disease) virus in vaccinated pigs and cattle in Ho Chi Minh City, as a basis to serve the prevention of FMD epidemics in these animals. A total of 535 pigs and 366cattle sera were tested by using the Elisa kit for the detection of serotype O FMD antibody (Pirbright, UK). Results of this study showed that most pig farms had the proportions of positive animals for antibodies against FMDV serotype O which met the requirements of Decision no. 07/2016/ Ministry of Agriculture and Rural Development, except Xuan Thoi Thuong, Thai My and Phu My Hung. All sows had high levels of antibodies against serotype O FMD virus. There were no significant differences in the ratios of positive pigs for antibodies against FMDV serotype O among types of pig and age groups. However, there were significant differences in the seroprevalence of vaccinated pigs across herd sizes and days post-vaccination. Meanwhile, the overall seroprevalence of vaccinated cattle against FMDV at individual-level was over 80.00%. No statistical differences were found in the seroprevalence of vaccinated cattle against type OFMDV among regions, types of cattle, herd sizes, age groups and days post-vaccination. In conclusion, pigs raised in farms of Xuan Thoi Thuong, Thai My and Phu My Hung communes should be revaccinated with FMD vaccine to prevent the risk of pigs being infected with FMD virus and reduce the amount of virus produced by an infected animal.

Background and objectives Deprescribing, the supervised withdrawal of inappropriate medications, intends to manage polypharmacy, which is prevalent in older patients. This study aimed to examine general practitioner (GP) perceptions of communication processes between clinicians in hospital and GPs in the community about deprescribing decisions made in hospital. Method Focus groups and interviews were held with 15 GPs, exploring deprescribing in hospitals, communication of deprescribing information, and the format of communications. Sessions were audio-taped, transcribed and analysed using an inductive approach. Results GPs stated that they should be involved in deprescribing decisions, especially for older complex patients, because of their good knowledge of their patients. Barriers to effective communication included the acute nature of hospital stays and lack of time. Facilitators included long-term relationships of GPs with their patients and engaged patients. GPs preferred communication of deprescribing decisions to be over the telephone while the patient was still in hospital, and with a concise, electronic discharge summary at the time of discharge. GPs indicated that rationale for medication changes and recommended follow-up actions were crucial in a discharge summary to enable care post-discharge. Conclusions GPs welcome increased communication with hospital clinicians regarding deprescribing decisions made while patients are in hospital. Communication needs to be timely, transparent, succinct and accessible. Lack of time and difficulties contacting hospital clinicians challenge this process. This article is protected by copyright. All rights reserved.

Background There are many barriers to deprescribing in the routine care of older inpatients with polypharmacy. Implementation is limited by factors related to clinicians, patients, and the acute care setting. A short (11 min) e-learning module for multidisciplinary hospital clinicians was developed to address two commonly reported barriers: awareness of polypharmacy and self-efficacy in deprescribing. Objectives 1) Describe the level of awareness of polypharmacy and self-efficacy of deprescribing in multi-disciplinary hospital clinicians following completion of an online e-learning module; and 2) describe the immediate impact of an online educational module in awareness and self-efficacy of polypharmacy and deprescribing in senior medical students. Methods A questionnaire was developed and administered to hospital clinicians following completion of the e-learning module. Senior medical students undertook the questionnaire pre- and post-module. Results Overall, 99 hospital clinicians with diverse clinical roles, experience, and ages, and 30 medical students completed the questionnaire. Although most (≥80%) hospital clinicians reported a general awareness of polypharmacy and deprescribing, there was moderate to low current activity in medication review and deprescribing, a perceived lack of role in medication review by junior doctors, and minimal knowledge of deprescribing tools. Use of a previously validated self-efficacy questionnaire showed lowest self-efficacy in domains related to developing deprescribing plans and implementing them. Pre-post analysis of medical student responses found a small statistically significant improvement following viewing the module in awareness of polypharmacy, deprescribing and deprescribing tools, perception of their role in deprescribing, and self-efficacy in planning and implementation of deprescribing decisions. Conclusions Hospital clinicians and senior medical students had limited self-efficacy in deprescribing and hospital clinicians reported they did not deprescribe frequently. Targets for educational and behavioral interventions were identified. A short e-learning module on polypharmacy and deprescribing may be a useful component of a multi-strategic intervention to implement deprescribing into routine inpatient care.

This article discusses the dynamism of Vietnam's social media landscape by identifying three kinds of blogging and the different political views espoused by Vietnamese bloggers. This classification is based on a thematic analysis of blog postings, media discussions and semi-structured interviews conducted in 2013–15. The author's mapping of Vietnam's blogosphere demonstrates four features: first, the growth of political blogs; second, how the blogosphere has become an arena for competing political ideologies; third, the utilization of blogs by various factions within the Communist Party of Vietnam (CPV) to serve their own interests; and fourth, blogs as an important source of independent news and information. Understanding political blogs in Vietnam today helps us understand how Vietnamese bloggers maximize online freedom of speech, the zigzagging attitude of the CPV in managing the Internet in an attempt to reinforce its legitimacy and the challenges blogs pose to the state-run media's monopoly in the digital age.

ObjectiveTo develop information leaflets for older inpatients and/or their carers to support deprescribing of antipsychotics, benzodiazepines/Z-drugs and proton pump inhibitors (PPIs).DesignAn iterative mixed-methods approach involving face-to-face user testing and semi-structured interviews was performed over three rounds with consumers and hospital health professionals.SettingSydney, New South Wales, Australia.ParticipantsThirty-seven consumers (or their carers) aged 65 years or older admitted to hospital in the previous 5 years and taking at least one regular medicine (not the medicine tested) completed user testing. Health professionals included a convenience sample of seven pharmacists and five doctors.MethodsThe antipsychotic leaflet was tested in round 1 (consumers, n=10) and revised and retested in round 2 (consumers, n=9; health professionals, n=5). Findings from rounds 1 and 2 informed the design of the benzodiazepine/Z-drug and PPI leaflets tested in round 3 (benzodiazepine/Z-drug consumers, n=9; health professionals, n=7; PPI consumers, n=9). Findings from round 3 informed the final design of all leaflets. Consumer user testing involved 12–13 questions to evaluate consumers’ ability to locate and understand information in the leaflet. Usability by health professionals was assessed using the System Usability Scale (SUS).ResultsAt least 80% of consumers correctly found and understood the deprescribing information in the leaflets (9 of 12 information points in round 1 (antipsychotic); 10 of 12 in round 2; 12 of 13 (benzodiazepine/Z-drug) and 11 of 12 (PPI) in round 3). Consumers perceived the leaflets to be informative, well-designed and useful aids for ongoing medication management. The SUS scores obtained from health professionals were 91.0±3.8 for the antipsychotic leaflet and 86.4±6.6 for the benzodiazepine/Z-drug leaflet, indicating excellent usability.ConclusionsUnderstandable and easy-to-use consumer information leaflets were developed and tested by consumers and health professionals. The feasibility and utility of these leaflets to support deprescribing at transitions of care should be explored in clinical practice.

Background The current UK vaccination programme for herpes zoster (HZ) excludes people aged ≥80 years. This study aimed to quantify the number of individuals ≥80 years who missed HZ vaccination and the consequent epidemiological and economic burden of HZ and post-herpetic neuralgia (PHN). Methods Immunocompetent individuals aged ≥80 years between 1st September 2013 and 31st December 2017 in the Clinical Practice Research Datalink were selected and linked to Hospital Episodes Statistics, where available. Rates of HZ and PHN and healthcare resource utilisation were investigated for the overall study population and by age group (80–84, 85–89, ≥90 years old) and the burden of HZ and PHN was projected to the UK population. Results 4,858 HZ episodes and 464 PHN cases were identified in 255,165 individuals over 576,421 person-years (PY). Rates of HZ and PHN were 8.43 (95% confidence interval [CI] 8.19–8.66) and 0.80 (0.73–0.87) per 1,000 PY respectively and lowest in those aged ≥90 (HZ rate 7.37/1,000 PY; PHN rate 0.56/1,000 PY). Within HZ episodes, 10.27% of GP visits, 5.82% of prescribed medications and 21.65% of hospitalisations were related to HZ/PHN. Median length of hospitalisation increased from 7.0 days for all-cause to 10.5 days for HZ/PHN related hospitalisations. Individuals ≥90 stayed in hospital a median of 3–4 days longer than younger groups. Approximately 2.23 million individuals in the UK missed HZ vaccination since 2013 (1.86 million had never been eligible and 365,000 lost eligibility for HZ vaccination), resulting in an estimated 43,149 HZ episodes. Conclusion This study highlights the impact of the 80-year upper age limit policy on the health system. Our study estimates that 2.23 million individuals in the UK may have lost the opportunity to be vaccinated and that their burden of HZ and PHN remains high, especially among the very elderly.

ObjectivesTo inform the design of electronic decision support (EDS) to facilitate deprescribing in hospitals we set out to (1) explore the current processes of in-hospital medicines review, deprescribing and communication of deprescribing decisions with the patient’s general practitioner (GP), (2) identify barriers to undertaking these tasks and (3) determine user preferences for EDS.DesignMultimethod, multisite study comprising observations, semistructured interviews and focus groups.SettingGeneral medicine, geriatric medicine and rehabilitation wards at six hospitals in two local health districts in Sydney, Australia and primary care practices in one primary healthcare district in Sydney, Australia.Participants149 participants took part in observations, interviews and focus groups, including 69 hospital doctors, 13 nurses, 55 pharmacists and 12 GPs.Main outcome measuresObservational data on who was involved in medicines review and deprescribing, when medicines review took place, and what artefacts (eg, forms) were used. Participants reported perceptions of medicines review, polypharmacy and deprescribing and preferences for EDS.ResultsDeprescribing, undertaken during medicines review, was typically performed by a junior doctor, following a decision to deprescribe by a senior doctor. Key barriers to deprescribing included a perception that deprescribing was not the responsibility of hospital doctors, a lack of confidence among junior doctors and pharmacists in broaching this topic with senior doctors and a lack of patient engagement in the deprescribing process. In designing EDS, the tools, likely to be used by junior doctors, pharmacists and nurses, should be available throughout the hospitalisation and should comprise non-interruptive evidence-based guidance on why and how to deprescribe.ConclusionsDeprescribing decisions are complex and influenced by multiple factors. The implementation of EDS alone is unlikely to address all barriers identified. To achieve sustained improvements in monitoring of polypharmacy and subsequent deprescribing, a multifaceted intervention is needed.

The cardiovascular (CV) risks of non-steroidal anti-inflammatory drugs (NSAIDs) are dose- and duration-dependent. As over-the-counter (OTC) NSAIDs are widely used for the treatment of common painful disorders, without medical supervision, their cardiovascular risks need to be assessed.Individual clinical trials and observational studies of the CV risks associated with NSAIDs and meta-analyses thereof were retrieved and analysed. The article focuses on the risk associated with low-dose ibuprofen and diclofenac, two drugs available OTC in many countries. Very few studies reported on dose-related CV risks of NSAIDs. The usual cut-off for low-dose ibuprofen was 1200 mg daily, the upper limit of the approved OTC daily dose. For diclofenac, the usual cut-off was 100 mg, 33% above the approved daily dose for OTC preparations (75 mg/day). Only one study reported on the CV risks of doses at or below this limit. The studies retrieved found a clear dose-dependent risk with both drugs and no clearly increased cardiovascular risk for doses at or below the maximal approved OTC doses. No study looked at actual OTC usage.At doses below the maximal daily OTC dose and for durations associated with OTC usage, there was no clear association with increased CV risk.

Proofreading, the act of checking first-draft writings performed by native experts, is essential for professional writing by non-native speakers. How to automatically proofread could be an interesting topic of NLP, but have not yet been well-explored. Our research carried out the first step toward automatic proof-reading by automatically analyzing the correspondences between original and proofreading texts. We propose a new task of word alignment in the context of writing assistance application, called word alignment for writing assistance. This paper presents the task formulation and compares different methods in solving the task. Our experimental results show that the best method achieved 71.8% in accuracy.

OBJECTIVE:To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an "essential" medicine, and how the Essential Medicines List (EML) concept functions in a high income country context. METHODS:In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach. FINDINGS:Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain. CONCLUSIONS:This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders considered were essential medicines, challenges whether the EML concept is out-dated or underutilised in high income countries.