bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant synthetic biology could drive a revolution in biofuels and medicine
Authors: Mortimer Jenny C 
Published: September 2018

Population growth, climate change, and dwindling finite resources are amongst the major challenges which are facing the planet. Requirements for food, materials, water, and energy will soon exceed capacity. Green biotechnology, fueled by recent plant synthetic biology breakthroughs, may offer solutions. This review summarizes current progress towards robust and predictable engineering of plants. I then discuss applications from the lab and field, with a focus on bioenergy, biomaterials, and medicine. Impact statement The plant synthetic biology field has exploded in the last five years, in part driven by techniques such as CRISPR and cheap DNA synthesis. This review summarizes the current state of research in plant synthetic biology, and how it is being applied to two topics: renewable fuels and chemicals, and medicine.
Examining patterns in opioid prescribing for non-cancer-related pain in Wales: preliminary data from a retrospective cross-sectional study using large datasets
Authors: Davies Emma , Phillips Ceri , Rance Jaynie , Sewell Berni 
Published: September 2018

Objectives: To examine trends in strong opioid prescribing in a primary care population in Wales and identify if factors such as age, deprivation and recorded diagnosis of depression or anxiety may have influenced any changes noted. Design: Trend, cross-sectional and longitudinal analyses of routine data from the Primary Care General Practice database and accessed via the Secure Anonymised Information Linkage (SAIL) databank. Setting: A total of 345 Primary Care practices in Wales. Participants: Anonymised records of 1,223,503 people aged 18 or over, receiving at least one opioid prescription between 1 January 2005 and 31 December 2015 were analysed. People with a cancer diagnosis (10.1%) were excluded from the detailed analysis. Results: During the study period, 26,180,200 opioid prescriptions were issued to 1,223,503 individuals (55.9% female, 89.9% non-cancer diagnoses). The greatest increase in annual prescribing was in the 18–24 age group (10,470%), from 0.08 to 8.3 prescriptions/1000 population, although the 85+ age group had the highest prescribing rates across the study period (from 149.9 to 288.5 prescriptions/1000 population). The number of people with recorded diagnoses of depression or anxiety and prescribed strong opioids increased from 1.2 to 5.1 people/1000 population (328%). The increase was 366.9% in areas of highest deprivation compared to 310.3 in the least. Areas of greatest deprivation had more than twice the rate of strong opioid prescribing than the least deprived areas of Wales. Conclusion: The study highlights a large increase in strong opioid prescribing for non-cancer pain, in Wales between 2005 and 2015. Population groups of interest include the youngest and oldest adult age groups and people with depression or anxiety particularly if living in the most deprived communities. Based on this evidence, development of a Welsh national guidance on safe and rational prescribing of opioids in chronic pain would be advisable to prevent further escalation of these medicines. Summary points This is the first large-scale, observational study of opioid prescribing in Wales. Over 1 million individual, anonymised medical records have been searched in order to develop the study cohort, thus reducing recall bias. Diagnosis and intervention coding in the Primary Care General Practice database is limited at input and may lead to under-reporting of diagnoses. There are limitations to the data available through the Secure Anonymised Information Linkage databank because anonymously linked dispensing data (what people collect from the pharmacy) are not currently available. Consequently, the results presented here could be seen as an ‘intention to treat’ and may under- or overestimate what people in Wales actually consume.
The Effect of N-Acetylcysteine on Creatinine Measurement: Protocol for a Systematic Review
Authors: Huang Johnny W. , Clarkin Owen J. , McCudden Christopher , Akbari Ayub , Chow Benjamin J. W. , Shabana Wael , Kanji Salmaan , Davis Alexandra , Hiremath Swapnil 
Published: September 2018

Background: N-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, a systematic review of the literature will be conducted to determine whether there is an effect of NAC on kidney function measured with serum creatinine. Objective: To determine the effect of NAC on kidney function. Design: A systematic review and meta-analysis. Settings: Prospective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery). Patients: Adult humans aged 18 years old or more, either healthy volunteers or with chronic kidney disease, were administered with NAC. Populations having little to no kidney function such as in end-stage kidney disease will be excluded. Measurements: Serum creatinine and/or cystatin C measurements before and after NAC administration. Methods: An information specialist will assist in searching MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify all study types including randomized controlled trials, and prospective cohort studies reporting change in serum creatinine after NAC administration. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using predefined inclusion criteria and will then extract data from the full texts of selected studies. The weighted mean difference will be calculated for change in creatinine with NAC, using random-effects analysis. Quality assessment will be done with the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. Results: The outcome of interest is kidney function as reported by either change in serum creatinine and/or serum cystatin C measurement for randomized trials or comparing baseline (pre-NAC dose) values and those following the NAC dose. Limitations: Possible heterogeneity and publication bias and lack of mechanistic data. Conclusions: This systematic review will provide a synthesis of current evidence on the effect of NAC on serum creatinine measurement. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field. Systematic review registration: This review is registered with PROSPERO, CRD42017055984
Low Potency of Indian Dust Mite Allergen Skin Prick Test Extracts Compared to FDA-Approved Extracts: A Double-Blinded Randomized Control Trial
Authors: Christopher Devasahayam J. , Ashok Narmada , Ravivarma Aruna , Shankar Deepa , Peterson Erik , Dinh Phuong T. , Vedanthan P. K. 
Published: September 2018

Background Skin prick testing is the most important diagnostic tool to detect immunoglobulin E-mediated allergic diseases. With increase in the number of allergy tests performed in India, it is imperative to know the potency of indigenous extracts in comparison with U.S. Food and Drug Administration (USFDA)-approved extracts. Methods A randomized comparison trial of Indian manufactured and USFDA-approved extracts of Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) was done at Christian Medical College & Hospital, Vellore, India from April 2014 to June 2015, to compare the skin test reactivity of indigenous allergen extracts of dust mites against validated allergen. Study enrollment included 197 patients with allergic disorders that showed sensitivity to dust mite during routine allergy skin testing. Study participants were tested with varying dilutions of DP and DF indigenous extracts along with USFDA-approved allergens in a blinded fashion. Results were recorded, and statistical significance was calculated using the Friedman rank sum test. Results Using the Friedman rank sum test with a Tukey adjustment for multiple comparisons, we found that the extracts in each dilution were significantly different ( P < .0001). The full strength indigenous extracts, B-DF (DF allergen standard extract from Bioproducts and Diagnostics, India) and C-DF (DF allergen extract from Creative Diagnostics, India) extracts, had mean wheal sizes of 7.69 (standard deviation [SD] 9.91) and 31.01(SD 51.04), respectively. The full strength S-DF (DF allergen extract from Jubilant Hollister Stier, Spokane, WA, USA) had a mean wheal size of 109.97 (SD 162.73), which was significantly higher ( P < .0001) than both the indigenous extracts. For each of the dilutions, the S-DF mean wheal size was significantly greater than that of the corresponding B-DF and C-DF wheal sizes. The full strength indigenous C-DP (DP allergen extract from Creative Diagnostics, India) had mean wheal size of 39.37 (SD 51.74). The full strength standard S-DP (DP allergen extract from Jubilant Hollister Stier, Spokane, WA, USA) extract had a mean wheal size of 167.66 (SD 270.80), which was significantly higher ( P < .0001) than the indigenous C-DP extract. Similar differences were seen across all dilutions. Conclusion The indigenous extracts have significantly lower potency compared to USFDA-approved extracts; hence, there is an urgent need for policy makers to institute stringent criteria for standardization of antigens in India.
Upscaling lithology and porosity-type fractions from the micro- to the core-scale with thin-section petrography, dual-energy computed tomography, and rock typing: Creation of diagenesis and porosity-type logs
Authors: Proctor Jacob M. , Droxler André W. , Derzhi Naum , Hopson Heath H. , Harris Paul (Mitch) , Khanna Pankaj , Lehrmann Daniel J. 
Published: September 2018

We have developed and validated a new approach to upscale lithology and porosity-type fractions from thin sections to cores using dual energy and multiscale computed tomography (CT). A new rock-typing approach (genetic rock typing [GRT]) is proposed to upscale ⇋diagenetic mineral and diagenetic pore-type fractions, from thin sections to the core domain, eventually to create a diagenesis and porosity types logs. An extensive set of short cores from Mason County (Texas) provides a representative sample set of Late Cambrian microbial buildups and their interbuildup sediments to test the GRT approach. GRTs were defined by using a dolomite log as a proxy for diagenesis and the average percentage of dolomite from each observed depositional facies (buildup interior, buildup rind, and interbuildup sediment) as a cutoff. Dolomite, diagenetic calcite, and diagenetic porosity fractions are summed to form a diagenesis log, which captures depositional facies and the diagenetic overprint at a 0.5 mm resolution. The diagenesis log was subdivided based on the number of pore-throat size classes within each GRT and provided a framework to distribute porosity-type fractions from thin sections to log form. A high correlation coefficient is observed when the predicted extent of diagenetic alteration from the log is compared with that quantified for each thin section using image processing ([Formula: see text]). Multiscale CT imaging and dual-energy-derived logs could be directly linked to well-log photoelectric factor and bulk-density logs. This approach thus has the ability to span six orders of magnitude in resolution (500–0.0005 mm). The diagenesis log can be used to extrapolate porosity-type fractions from thin sections to logs, from which qualitative geologic interpretations can be generally translated into quantitative values.
How nonrandomized trials (NRT) inform pan-Canadian Oncology Drug Review (pCODR) expert review committee (pERC) recommendations in blood cancer.
Authors: Tiruneh Missale , Ross Stephanie , Ellis Kristina , Trudeau Maureen E. , Moltzan Catherine , McDonald Valerie , Chambers Alexandra , Haynes Adam E. 
Published: September 2018

100 Background: In Canada, the Canadian Agency for Drugs and Technologies in Health’s pERC makes reimbursement recommendations for cancer drugs based on pCODR reviews of best available evidence, which in some circumstances, is from Phase II NRTs. To date, the majority of pERC recommendations based on NRT evidence have been for blood cancers. Objective: To examine aspects of NRT evidence that may influence pERC reimbursement recommendations for blood cancers. Methods: Final pERC Recommendations on blood cancer reviews supported by NRTs were included (July 2011 to June 2018). Factors that influenced Final Recommendations, such as clinical benefit, alignment with patient values and cost-effectiveness, were extracted. Results: As of June 2018, 10 conditional and 6 negative decisions were made in 13 Final Recommendations. Among conditional reimbursement recommendations, substantial need for treatment options and poor prognosis with available therapies were commonly noted. Assessment of the feasibility of randomized controlled trials (RCT) varied. The magnitude of benefit was impressive or a substantial benefit was seen in subgroups with greater need. Some recommendations noted benefit above historical outcomes or consistent evidence with other indications or trials. Most recommendations reported an improvement in quality of life (QoL) and a manageable toxicity profile. Limitations included short trial follow-up. Factors affecting cost-effectiveness and alignment with patient values varied. Among negative recommendations, there was less certainty about burden of illness and need. Uncertainty about magnitude of clinical benefit was attributed to lack of direct or indirect comparison to available options, lack of long term data or comparison to historical evidence, limited QoL data, and variability in toxicity. All cases were not cost-effective and partially aligned with patient values. Conclusions: pERC may accept evidence from NRTs to make reimbursement recommendations for blood cancers when there is a high burden of illness, unmet need, reasonable demonstration of efficacy and manageable toxicities. Feasibility of RCT was not a consistent factor.
Impact of novel chronic lymphocytic leukemia drugs on public spending.
Authors: Mow Elena , Keech James , Naipaul Rohini , Beca Jaclyn Marie , Gavura Scott , Kouroukis C. Tom 
Published: September 2018

103 Title: Impact Of Novel Chronic Lymphocytic Leukemia Drugs On Public Spending Background: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy that mainly affects the elderly. Over the past five years, the treatment pathway for CLL has dramatically changed with the emergence of multiple novel agents. In Ontario, Canada, the Ontario Drug Benefit (ODB) program and the New Drug Funding Program (NDFP) primarily provide public coverage for CLL drugs. Given advances in treatment, we evaluated utilization trends for publicly-funded CLL drugs over a five year period (fiscal years 2012/13 to 2016/17). Methods: Drugs with primary CLL indications funded under the two public funding programs (i.e., ODB and NDFP) by 16/17 were included (n = 6). Claims and costs data were obtained from the Institute for Clinical Evaluative Sciences and Cancer Care Ontario‘s datasets. Results: Over five years, expenditures on CLL drugs have increased approximately ten-fold (1000 percent), reaching nearly CAD 43 million (i.e., USD 32.8 million) in 16/17. In the front-line setting, spending on rituximab remained consistent over the five years. Spending on single agent bendamustine decreased with the introduction of obinutuzumab which became the main cost driver by 16/17. In the previously-treated CLL population, ibrutinib has dominated expenditures since it was funded in July 2015. By 16/17, ibrutinib accounted for approximately ninety eight percent of spending in the previously-treated population. Conclusions: In the past five years, public spending on CLL drugs increased rapidly and substantially with the introduction of four novel agents, and may continue to evolve as Canadian provinces consider funding additional indications or newer agents. These findings warrant exploring whether the incremental spending is providing survival benefit or improvement in patients’ quality of life in a real-world setting. Declaration of funding: None
Washington State Community Cancer Care Report: Implications for value-based purchasing.
Authors: Panattoni Laura Elizabeth , Sun Qin , Fedorenko Catherine R. , Kreizenbeck Karma L. , Ramsey Scott David 
Published: September 2018

104 Background: As quality reports are released for regions and individual clinics, an important question is whether those reports can be used for value based purchasing, particularly for community oncology clinics. We evaluated the reliability of select quality measures and estimated the likelihood that a clinic’s performance would be incorrectly categorized (misclassified) in the top quartile. Methods: We linked 2014-2016 cancer registry records for patients with enrollment and claims from Medicare and two major commercial insurers in Washington State. We calculated risk standardized rates (RSRs) for ED and hospital use during treatment and 3 quality measures for end of life care. Reliability (0-1 scale: 0-unreliabile, > 0.7 good reliability, 1 perfectly reliable) was calculated as signal/(signal + statistical noise) from hierarchical logistic regression modeling for each metric. Misclassification was characterized as the probability of false negative and false positive assignment of clinics to the top quartile of performers in the region. We generated results for 3 and 1 year performance periods. Results: Over the 3 year period, the hospitalization metrics included 7,373 patients, 25 clinics; end of life metrics included 8,165 patients; 24 clinics. Conclusions: Although these metrics had fairly high levels of reliability, approximately one-third of clinics could be incorrectly identified as a top quartile performer. Use of these metrics in value based purchasing should account for potential misclassification to minimize unintended consequences.[Table: see text]
Education, engagement, and MIPS: The new era of accountability.
Authors: Denny, DBA Diane , Gross Danielle , Markman Maurie 
Published: September 2018

111 Background: As 2017 marked the start of CMS’ new Quality Payment Program (QPP), a national network of hospitals worked together with its physician practices to ensure maximum participation and benefit. Each practice consisted of multi-specialists collaborating in the treatment of oncology patients and reporting through the American Society of Clinical Oncology qualified data registry. Methods: A team was created with the primary tasks of 1) transitioning and ensuring readiness; 2) selecting and reporting on measures of interest associated with two QPP categories, Quality and Improvement Activities (IAs) and 3) educating its practices on the merits of participation. This included the creation of infographics titled MACRA 101, 201, 301 and a detailed Q&A tool for maintaining information exchange. The former was a progressive approach to educating on the law, that success is a team sport, and that public reporting of performance data is here to stay, concluding with a call to action. Results: Oncology measures were reported for the full CY17 as follows. The same quality improvement activity of data capture, metric review and process re-design became the narrative for the practices’ selection of its two required IAs. Conclusions: Although year one allowed for lesser requirements to enable transition, positioning the practices to report at the maximum level resulted in strong physician-hospital collaboration as well as the potential for financial and reputational gain. An unintended benefit was the realization that mandatory discrete fields in the practices’ EHR would benefit the practitioners in the long term as resource requirements needed to abstract from free-text is not sustainable.[Table: see text]
Changes in lung cancer screening knowledge, beliefs, and practices among health care providers.
Authors: Henderson Louise , Bearden Caitlin , Reuland Dan , Brenner Alison Tytell , Goldstein Adam , Maygarden Susan , Rivera M. Patricia 
Published: September 2018

117 Background: In 2013, the U.S. Preventative Task Force began recommending lung cancer screening (LCS) annually for patients ages 55-80 years who are current or former (quit within the last 15 years) smokers with a 30 pack-year history. Since then, the proportion of eligible patients undergoing LCS has been reported to be low, ranging from 3-5%. We sought to compare LCS practices and beliefs among health care providers at a large academic medical center from 2015 to 2018. Methods: In 2015 and 2018, we surveyed physicians and residents in pulmonology, family, and internal medicine using a 23-item Qualtrics survey developed with the Tailored Design Method. To evaluate potential workforce issues in LCS we compared responses regarding provider’s opinions, referral patterns, and barriers to LCS from 2015 to 2018 using chi-squared tests. Results: Response rates were 39% in 2015 and 26% in 2018. From 2015 to 2018 there was an increase in the proportion of providers who reported LCS as beneficial (44.6% vs 75.7%, p < 0.0001), cost effective (20.0% vs 38.6%, p = 0.002), and as having enough knowledge to explain the risks and benefits of LCS (53.6% vs 75.7%, p = 0.001). In both years, the majority of providers reported time restrictions during a patient’s clinic visit meant that other problems had higher priority than LCS (65.1% vs 71.4%, p = 0.85). Over the 3-year period the proportion of providers who reported ordering a LCS exam more than doubled (32.2% to 74.6%, p < 0.00001) and the percentage who initiated discussion about the risks and benefits increased from 45.9% to 87.3%. The proportion of providers who reported that a patient asked about LCS increased (22.8% to 37.7%, p = 0.001). While some reported barriers did not change from 2015 to 2018 (concern regarding false negatives, false positives, cost to system/patients, or potential for physical/emotional harm), more providers reported low patient acceptance or adherence (7.4% vs 13.0%, p = 0.01). Conclusions: From 2015 to 2018 healthcare providers reported a more favorable opinion of LCS and a higher proportion of providers reported ordering a LCS exam. Time constraints during the patient visit remained an issue and a higher proportion reported low patient acceptance/adherence as a barrier.