Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction

<p>Abstract</p> <p>Background</p> <p>Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR) incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process.</p> <p>Methods</p> <p>The inclusion criteria for patients in this study are: (1) had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2) suffered from serious ADRs, and (3) were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients.</p> <p>Results</p> <p>Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level) were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model.</p> <p>Conclusion</p> <p>Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.</p

Comparing factors affecting commencement and cessation of betel quid chewing behavior in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>Betel quid is the fourth most common used substance in the world after tobacco, alcohol and caffeine. Although factors related to betel quid chewing or cessation of behaviors were reported previously, few studies simultaneously compared both behaviors in the same population. In addition, it is essential to consider time-to-event concept, since the chance of developing or stopping habit may vary over time. The purpose of this study was to compare the risk factors for commencement and cessation of betel quid chewing behaviors in a time-to-event setting.</p> <p>Methods</p> <p>A stratified multi-stage cluster sampling with selection probabilities proportional to size (PPS) was designed for Taiwanese adults with aged 18 years old and above. Kaplan-Meier estimates and Cox proportional hazard regression models were used to compare and calculate the hazard rate ratios for related factors to commencement or cessation of chewing habits.</p> <p>Results</p> <p>In Taiwan, men had a higher betel quid chewing rate (M: 20.9%, W: 1.2%), but woman chewers had a lower cessation rate (M: 27.5%, W: 12.7%). The hazard rate ratio (HRR) of having chewing habit changed from 4.22 (men vs women) univariately to 1.38 multivariablely, which indicated gender differences were confounded by other factors. In multivariable analysis, the risk factors of gender, education and ethnicity were significantly associated with both starting and cessation of betel quid chewing behavior. The factors of occupation, cigarette smoking and alcohol drinking were only associated with starting habit.</p> <p>Conclusion</p> <p>Commencement or cessation of chewing behavior involves a scenario of time, hence it is preferable to use a time-to-event approach for the comparison. The cessation rates of betel quid chewing were decreasingly associated with the daily consumption of betel quid. Hence, reducing of daily amount in betel quid cessation program may be associated with future stopping habit.</p

User Preferences and Persona Design for an mHealth Intervention to Support Adherence to Cardiovascular Disease Medication in Singapore: A Multi-Method Study.

BACKGROUND: The use of mobile health (mHealth) has gained popularity globally, including for its use in a variety of health interventions, particularly through short message service (SMS) text messaging. However, there are challenges to the use of mHealth, particularly among older users who have a large heterogeneity in usability and accessibility barriers when using technology. OBJECTIVE: In order to better understand and conceptualize the diversity of users and give insight into their particular needs, we turned to persona creation. Personas are user archetypes created through data generated from multi-method inquiry with actual target users. Personas are an appropriate yet largely underutilized component of current mHealth research. METHODS: Leveraging data from a multi-method study conducted in Singapore with an ethnically diverse population including Chinese, Malay, and Indian participants, we used a proforma to analyze data from the qualitative component (ie, 20 in-depth interviews) and quantitative component (ie, 100 interviewer-guided surveys). We then identified key characteristics, including technology use and preferences as well as adherence factors, to synthesize five personas reflective of persons over the age of 40 years in Singapore with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors, such as hypertension. RESULTS: We present five personas typologized as (1) The Quiet Analog, (2) The Busy Grandparent, (3) The Socializer, (4) The Newly Diagnosed, and (5) The Hard-to-Reach. We report on four key characteristics: health care access, medication adherence, mobile phone technology usage (ie, ownership, access, and utilization), and interest in mHealth. Finally, we provide insights into how these personas may be used in the design and implementation of an mHealth intervention. Our work demonstrates how multi-method data can create biopsychosocial personas that can be used to explore and address the diversity in behaviors, preferences, and needs in user groups. CONCLUSIONS: With wider adoption of mHealth, it is important that we consider user-centered design techniques and design thinking in order to create meaningful, patient-centered interventions for adherence to medications. Future research in this area should include greater exploration of how these five personas can be used to better understand how and when is best to deliver mHealth interventions in Singapore and beyond

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds

Bacterial biofilms pose a therapeutic challenge to managing chronic wounds and contribute to antimicrobial resistance. Here, Powell et al. investigated the structure/activity relationships of epoxy-tigliane compounds derived from the blushwood tree with respect to their role in wound healing. The compounds interacted with the cell wall of bacteria but showed variable permeabilization in Gram-negative versus Gram-positive cultures. They disrupted established biofilms by interacting with the extracellular polymeric substance matrix, activated immune cells to induce reactive oxygen species, and promoted wound healing in infected thermal injuries in calves when applied topically. In chronic wounds in diabetic mice, the semisynthetic compound EBC-1013 up-regulated host-defense peptides, altered cytokine expression, activated immune cells, and led to greater wound closure. Results help uncover the mechanism by which epoxy-tiglianes promote wound healing and support further development of EBC-1013

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

A modified technique of pancreaticogastrostomy with short internal stent: A single surgeon's experience

Summary: Background/Objective: Postoperative pancreatic fistula (POPF) remains an important cause of morbidity and mortality after pancreaticoduodenectomy. Pancreaticogastrostomy (PG) as a reconstruction method after pancreaticoduodenectomy is a safe and optional surgical technique in decreasing the risk of POPF. In this study, a retrospective analysis was carried out to evaluate a new modification of PG technique that uses a two-layer anastomoses with an internal stent. Methods: Forty-seven patients underwent this newly modified PG technique between February 2012 and August 2016. Demographics, histopathological findings, type of surgery performed, perioperative parameters, postoperative length of stay, postoperative complications and interventional procedures, follow-up, and mortality data were collected and analyzed. Clavien–Dindo classification was used to grade the complications' severity. Results: Postoperative mortality was 4.25%, unrelated to POPF, and postoperative morbidity was 44.68%. Thirteen patients had severe (>Grade IIIa) complications, according to Clavien–Dindo classification. As classified in accordance to the International Study Group of Pancreatic Fistula, 24 (51.06%) patients developed Grade A POPF, and no occurrence of Grade B/C POPF was noted. All patients recovered uneventfully with successful treatment interventions. Conclusion: The reported PG anastomotic technique is a safe and dependable reconstruction procedure with acceptable morbidity and mortality. Keywords: pancreaticoduodenectomy, pancreaticogastrostomy, postoperative pancreatic fistul

Differences in expression of key DNA damage repair genes after epigenetic-induced brcaness dictate synthetic lethality with PARP1 inhibition

The triple-negative breast cancer (TNBC) subtype represents a cancer that is highly aggressive with poor patient outcome. Current preclinical success has been gained through synthetic lethality, targeting genome instability with PARP inhibition in breast cancer cells that harbor silencing of the homologous recombination (HR) pathway. Histone deacetylase inhibitors (HDACi) are a class of drugs that mediate epigenetic changes in expression of HR pathway genes. Here, we compare the activity of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), the class I/IIa HDAC inhibitor valproic acid (VPA), and the HDAC1/2-specific inhibitor romidepsin (ROMI) for their capability to regulate DNA damage repair gene expression and in sensitizing TNBC to PARPi. We found that two of the HDACis tested, SAHA and ROMI, but not VPA, indeed inhibit HR repair and that RAD51, BARD1, and FANCD2 represent key proteins whose inhibition is required for HDACi-mediated therapy with PARP inhibition in TNBC. We also observed that restoration of BRCA1 function stabilizes the genome compared with mutant BRCA1 that results in enhanced polyploid population after combination treatment with HDACi and PARPi. Furthermore, we found that overexpression of the key HR protein RAD51 represents a mechanism for this resistance, promoting aberrant repair and the enhanced polyploidy observed. These findings highlight the key components of HR in guiding synthetic lethality with PARP inhibition and support the rationale for utilizing the novel combination of HDACi and PARPi against TNBC in the clinical setting. (C) 2015 AACR