Combining precision medicine and prophylaxis in oesophageal squamous cell carcinoma

A trial update confirms improved survival for prophylactic elective nodal irradiation and addition of erlotinib to definitive chemoradiotherapy in oesophageal squamous cell carcinoma (ESCC). High tumour EGFR protein expression shows promise to identify those who will benefit from erlotinib. This represents therapeutic progress, and has wider relevance for precision medicine strategies in ESCC

Association of Infectious Disease Physician Approval of Peripherally Inserted Central Catheter With Appropriateness and Complications

Importance: Peripherally inserted central catheters (PICCs) are frequently used to deliver intravenous antimicrobial therapy. However, inappropriate PICC use may lead to patient harm. Objective: To evaluate whether infectious disease physician approval prior to PICC placement for intravenous antimicrobials is associated with more appropriate device use and fewer complications. Design, Setting, and Participants: This cohort study of 21 653 PICCs placed for a primary indication of intravenous antimicrobial therapy between January 1, 2015, and July 26, 2019, was conducted in 42 hospitals participating in a quality collaborative across Michigan among hospitalized medical patients. Main Outcomes and Measures: Appropriateness of PICCs was defined according to the Michigan Appropriateness Guide for Intravenous Catheters as a composite measure of (1) single-lumen catheter use, (2) avoiding use of PICCs for 5 days or less, and (3) avoiding use of PICCs for patients with chronic kidney disease (defined as an estimated glomerular filtration rate/min/1.73 m2). Complications related to PICCs included catheter occlusion, deep vein thrombosis, and central line-associated bloodstream infection. The association between infectious disease physician approval, device appropriateness, and catheter complications was assessed using multivariable models, adjusted for patient comorbidities and hospital clustering. Results were expressed as odds ratios with 95% CIs. Results: A total of 21 653 PICCs were placed for intravenous antimicrobials (11 960 PICCs were placed in men [55.2%]; median age, 64.5 years [interquartile range, 53.4-75.4 years]); 10 238 PICCs (47.3%) were approved by an infectious disease physician prior to placement. Compared with PICCs with no documented approval, PICCs with approval by an infectious disease physician were more likely to be appropriately used (72.7% [7446 of 10 238] appropriate with approval vs 45.4% [5180 of 11 415] appropriate without approval; odds ratio, 3.53; 95% CI, 3.29-3.79; P \u3c .001). Furthermore, approval was associated with lower odds of a PICC-related complication (6.5% [665 of 10 238] with approval vs 11.3% [1292 of 11 415] without approval; odds ratio, 0.55; 95% CI, 0.50-0.61). Conclusions and Relevance: This cohort study suggests that, when PICCs were placed for intravenous antimicrobial therapy, infectious disease physician approval of PICC insertion was associated with more appropriate device use and fewer complications. Policies aimed at ensuring infectious disease physician approval prior to PICC placement for antimicrobials may improve patient safety

Interactions between anti-EGFR therapies and cytotoxic chemotherapy in oesophageal squamous cell carcinoma: why clinical trials might have failed and how they could succeed

Acknowledgements We thank Alice Savage for technical laboratory assistance. Funding The work undertaken was funded by Ninewells Cancer Campaign (Dundee) and Scottish Government Chief Scientist Office (Grant reference TCS/19/18).Peer reviewedPublisher PD

Assessing the impact of climate change on sweet potato in Uganda

Sweet potato is a mainstay of household food security and a major source of vitamin A across sub-Saharan Africa, and particularly in Uganda. Understanding how climate change is likely to impact on sweet potato would be useful for policymakers in Uganda making decisions to improve food security and increase resilience to climate shocks. However, sweet potato is an under-researched crop and the impacts of climate change have not been systematically analysed. The Sweet Potato Catalyst Project aims to assess the impacts of climate change on sweet potato in Uganda and develop ways for local stakeholders to access and assess this information to strengthen governance. This policy briefing note provides an overview of the research, the approach being taken and anticipated outcomes that will feed into the UNFCCC Koronovia Joint Work on Agriculture

Expanding Access to Parasite-based Malaria Diagnosis through Retail Drug shops in Tanzania: Evidence from a Randomized Trial and Implications for Treatment.

Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices.\ud Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing. A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT. Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509

Sweet potato production in Uganda in a changing climate: what is the role for fertilisers

This policy brief for the Ugandan Government covers the use of manure and inorganic fertilisers in sweet potato production, including how fertiliser use in sweet potato production can contribute to boosting yields, livelihood resilience, improving diets and fighting malnutrition in Uganda in the face of climate change

Storylines for decision-making: climate and food security in Namibia

Storylines are plausible descriptions of past or future events and can be used to characterise uncertainty through discrete possible futures. They thereby bridge the gap between global-scale future projections and local-scale impacts, providing decision-makers with useful information about potential impacts in multivariate systems despite large swathes of missing data. Here we demonstrate the storyline approach using the case of household food security in the Caprivi region of Namibia, an example of a complex system with multiple interacting drivers. We develop a network characterising influences on household food security, highlighting drivers that are affected by the local weather (with climate understood to constitute the collection of possible weather states). The network is used to understand the storyline leading to household impacts in 2013-14, a consumption year affected by flooding, and the effects of a range of interventions across wealth groups. Counterfactual storylines are also developed to characterise potential impacts under different local and national conditions. Through this we demonstrate how a storyline approach can embed local contextual information to provide decision-makers with comprehensible and assessable information about possible futures and interventions. We also highlight the importance of identifying common drivers, in this case the local weather, in producing plausible impact storylines

Febrile Neutropenia in Children: Etiologies, Outcomes, and Risk Factors with Prolonged Fever

Most studies of children with prolonged fever and neutropenia (PFN) have focused on invasive fungal disease (IFD) as the etiology of fever and not on other causes. Data are lacking regarding risk factors and adverse outcomes in pediatric cancer patients with PFN compared with those whose fevers resolve more rapidly. Retrospective medical record review was performed for all cancer patients with febrile neutropenia (FN) in the pediatric oncology unit at University of Chicago Medicine Comer Children’s Hospital from March 2009 to July 2016. Resolving febrile neutropenia (RFN), lasting less than 96 hours, and PFN episodes (≥ 96 hours) were compared to identify risk factors and outcomes associated with PFN. A total of 572 FN episodes were identified in 265 patients. PFN occurred in 119 (21%) FN episodes (50 patients) and RFN occurred in 453 (79%) FN episodes (215 patients). In multivariable analysis, autologous stem cell transplant (odds ratio [OR] 6.5, P 39°C at the time of presentation (OR 2.4, P<0.01) and absolute monocyte count (AMC) <100 cells/m3 (OR 2.7, P=<0.01) were independently associated with PFN. Pneumonia, neutropenic enterocolitis and IFD were more common etiologies of fever in PFN compared with RFN. Patients with PFN were more likely to be admitted to the pediatric intensive care unit [OR 3, (95%CI, 1.66%-5.28%), P<0.001] and had a trend toward higher 30-day mortality [OR 3.8, (95%CI, 0.52%-29.32%), P=0.07]. Patients with PFN are at increased risk for serious illness and death. A better understanding of the etiologies of PFN other than IFD is needed to be able to appropriately diagnose and treat this high-risk group

Fight and flight: Evidence of aggressive capitulation in the face of fear messages from terrorists

In an era of digital technology and the Internet, terrorists can communicate their threats directly to citizens of Western countries. Yet no research has examined whether these messages change individuals’ attitudes and behaviour, or the psychological processes underlying these effects. Two studies (conducted in 2008 and 2010) examined how American, Australian, and British participants responded to messages from Osama bin Laden that threatened violence if troops were not withdrawn from Afghanistan. Heightened fear in response to the message resulted in what we call “aggressive capitulation,” characterized by two different group-protection responses: (1) submission to terrorist demands in the face of threats made against one’s country, and (2) support for increased efforts to combat the source of the threat, but expressed in abstract terms that do not leave one’s country vulnerable. Fear predicted influence over and above other variables relevant to persuasion. Theoretical and practical implications are discussed