Getting your DUCs in a row - standardising the representation of Digital Use Conditions.

Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level. Furthermore, the specifics and granularity required are likely to vary depending on the ultimate contexts of use. All these factors confound alignment of institutional missions, funding objectives, regulatory and technical requirements to facilitate effective sharing. The presented work highlights the complexity and diversity of the problem, reviews the current state of the art, and emphasises the need for a flexible and adaptable approach. We propose Digital Use Conditions (DUC) as a framework that addresses these needs by leveraging existing standards, striking a balance between expressiveness versus ambiguity, and considering the breadth of applicable information with their context of use.

Systematic review of medication related osteonecrosis of the jaw (MRONJ) in patients undergoing only antiangiogenic drug therapy: surgery or conservative therapy?

Osteonecrosis of the jaw is a severe adverse condition affecting patients exposed to specific types of medications. Previous studies have highlighted that osteonecrosis of the jaw is triggered by invasive dental procedures and can be very challenging to manage, especially in patients with cancer. The primary aim of this review was to analyse all available evidence on the management (surgical and/or conservative) of medication related osteonecrosis of the jaws (MRONJ) in patients with a history of antiangiogenic drugs therapy and who had not been previously exposed to any antiresorptive drug treatments. A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until November 2020. Data were extracted from relevant papers and analysed according to the outcomes selected in this review. The search generated 28 studies eligible for the analysis. The total number of patients included in the analysis was 36. Sixteen patients were treated with anti-vascular endothelial growth factor drugs (anti-VEGF) while the remaining patients were administered a combination of antiangiogenic drugs. The most common MRONJ site was the mandible in 29 patients. MRONJ recurrence after treatment was only reported in six patients, the majority of which were treated conservatively. The data reviewed confirmed that an invasive procedure was the most common trigger of MRONJ with relatively high frequency of postoperative recurrence following treatment. However, due to the low quality of available research in the literature, it is difficult to draw a definitive conclusion on the validity of the presented treatment to manage patients affected by MRONJ associated with angiogenic therapy.

Postdischarge Health Care Costs and Readmission in Patients With Hyperkalemia-Related Hospitalizations.

INTRODUCTION: Limited evidence is available regarding the postdischarge economic and readmission burdens of hyperkalemia. METHODS: Using the IBM MarketScan Commercial and Medicare-Supplemental Claims database (January 1, 2010-December 31, 2014), adult patients with a hospitalization with a hyperkalemia diagnosis (ICD-9-CM 276.7, hyperkalemia cohort) were 1:1 matched with patients with a hospitalization without evidence of hyperkalemia (nonhyperkalemia cohort) on age, chronic kidney disease stage, heart failure, dialysis, renin-angiotensin-aldosterone system inhibitor use, and major diagnostic categories of the hospitalization. All-cause health care costs and health care resource utilization measures were compared between cohorts during the 1-year postdischarge period. Postdischarge readmission and length of stay (LOS) were compared between hyperkalemia-related hospitalizations from the hyperkalemia cohort and matched hospitalizations unrelated to hyperkalemia from the nonhyperkalemia cohort. RESULTS: Patients with hyperkalemia-related hospitalizations (n = 4426) incurred $30,379 (95% confidence interval, $25,423-$35,335) higher 1-year total all-cause costs ($68,861 vs. $38,482) and had higher rates of inpatient admissions (1.0 vs. 0.4), emergency department visits (2.0 vs. 1.2), and outpatient visits (49.6 vs. 39.1) than the nonhyperkalemia cohort during the 1-year postdischarge study period (all P < 0.001). Hyperkalemia-related hospitalizations (n = 5377) were associated with significantly higher readmission rates (within 30 days: 0.15 vs. 0.09; 60 days: 0.25 vs. 0.16; 90 days: 0.36 vs. 0.23; all P < 0.001), longer LOS per readmission (8.1 vs. 7.1 days), and longer total inpatient days (10.5 vs. 5.8 days) compared with hospitalizations unrelated to hyperkalemia (all P < 0.001). Similar trends were observed across comorbidity subgroups. CONCLUSION: Hyperkalemia-related hospitalizations were associated with significant economic and readmission burdens during the 1-year postdischarge period.

Prevalence and economic burden of hyperkalemia in the United States Medicare population.

Objective: To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population.Methods: Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010-31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated.Results: The estimated prevalence of hyperkalemia was 2.6-2.7% in the overall population and 8.9-9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (all p < .001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (both p < .001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (both p < .001).Conclusions: Hyperkalemia had an estimated prevalence of 2.6-2.7% in the Medicare population and was associated with markedly high healthcare costs.

Highlights from Faraday Discussion on Ultrafast Photoinduced Energy and Charge Transfer, Ventura, CA, USA, April 2019.

Following a tradition more than 100 years old, a Faraday Discussion meeting was held on the topic of 'Ultrafast Energy and Charge Transfer' in April 2019. While these meetings are historically held in the United Kingdom, the Royal Society of Chemistry (who organises the conference and publishes its proceedings) recognises the importance of finding the space and opportunity for the chemical sciences international communities to connect and exchange knowledge. As such, the meeting hereby referred to took place in Ventura, California, USA. This conference report, produced by early career researchers, covers the highlights of this meeting, focusing on brief summaries of the papers discussed as well as particularly interesting or recurring topics of the ensuing discussion.

Responsible sharing of biomedical data and biospecimens via the "Automatable Discovery and Access Matrix" (ADA-M).

Given the data-rich nature of modern biomedical research, there is a pressing need for a systematic, structured, computer-readable way to capture, communicate, and manage sharing rules that apply to biomedical resources. This is essential for responsible recording, versioning, communication, querying, and actioning of resource sharing plans. However, lack of a common "information model" for rules and conditions that govern the sharing of materials, methods, software, data, and knowledge creates a fundamental barrier. Without this, it can be virtually impossible for Research Ethics Committees (RECs), Institutional Review Boards (IRBs), Data Access Committees (DACs), biobanks, and end users to confidently track, manage, and interpret applicable legal and ethical requirements. This raises costs and burdens of data stewardship and decreases efficient and responsible access to data, biospecimens, and other resources. To address this, the GA4GH and IRDiRC organizations sponsored the creation of the Automatable Discovery and Access Matrix (ADA-M, read simply as "Adam"). ADA-M is a comprehensive information model that provides the basis for producing structured metadata "Profiles" of regulatory conditions, thereby enabling efficient application of those conditions across regulatory spheres. Widespread use of ADA-M will aid researchers in globally searching and prescreening potential data and/or biospecimen resources for compatibility with their research plans in a responsible and efficient manner, increasing likelihood of timely DAC approvals while also significantly reducing time and effort DACs, RECs, and IRBs spend evaluating resource requests and research proposals. Extensive online documentation, software support, video guides, and an Application Programming Interface (API) for ADA-M have been made available.

The Cost of Hyperkalemia in the United States.

INTRODUCTION: There are limited data on the cost of hyperkalemia. METHODS: This retrospective analysis of the Truven MarketScan claims database assessed the economic burden of hyperkalemia among selected adult patients with hyperkalemia and matched controls. RESULTS: A total of 39,626 cases (patients with hyperkalemia) were matched to 39,626 controls (patients without hyperkalemia) based on age, dialysis, chronic kidney disease (CKD) stage, heart failure, and renin-angiotensin aldosterone system inhibitor use. Compared with controls, cases incurred $4128 (95% confidence interval [CI] $3893-$4363) higher 30-day total health care costs ($5994 vs. $1865) and $15,983 (95% CI $15,026-$16,940) higher 1-year costs ($31,844 vs. $15,861). Among 11,221 matched pairs of patients with CKD and/or heart failure, cases incurred $5553 (95% CI $5059-$6047) higher 30-day total health care costs ($8165 vs. $2612) and $24,133 (95% CI $21,748-$26,518) higher 1-year costs ($48,994 vs. $24,861) than controls. The multivariable adjusted 1-year total health care cost difference was $15,606 (95% CI $14,648-$16,576) among all patients and $25,156 (95% CI $23,529-$26,757) among patients with CKD and/or heart failure. Cases had higher resource utilization rates including inpatient admissions (30-day: 0.14 vs. 0.03; 1-year: 0.44 vs. 0.19), outpatient visits (30-day: 3.33 vs. 2.28; 1-year: 26.58 vs. 18.53), and emergency department visits (30-day: 0.16 vs. 0.06; 1-year: 0.86 vs. 0.50) (all P < 0.001). When hospitalized, cases stayed 1.51 days (95% CI 1.22-1.80) longer and were 40% more likely to be readmitted. CONCLUSION: These data indicate that hyperkalemia is associated with a significant economic burden on afflicted patients and the health care system.

The prevalence of hyperkalemia in the United States.

OBJECTIVE: The retrospective study aimed to estimate prevalence of hyperkalemia using a large US commercial claims database. METHODS: Adults with serum potassium lab data (2010 to 2014) and ≥1 calendar year of data were included from a large US commercial claims database. Hyperkalemia was defined as ≥2 serum potassium measurements >5.0 mEq/L or one hyperkalemia diagnosis code (ICD-9-CM, 276.7) or one sodium polystyrene sulfonate fill. Hyperkalemia prevalence was estimated for the overall population and subgroups with hyperkalemia-related comorbidities by calendar year. Hyperkalemia prevalence was also standardized to the US population to estimate the number of US adults with hyperkalemia. RESULTS: The analysis included 2,270,635 patients (2010-2014). The annual prevalence of hyperkalemia in the overall population was 1.57% in 2014, with higher rates observed in patients with chronic kidney disease (CKD), heart failure, diabetes and hypertension. Among patients with CKD and/or heart failure, the 2014 annual prevalence was 6.35%. Among patients with hyperkalemia, 48.43% had CKD and/or heart failure in 2014. The prevalence of hyperkalemia was higher in patients with more severe CKD, as well as older patients and men. Extrapolating those results to the US population supports that 1.55% or 3.7 million US adults had hyperkalemia in 2014. CONCLUSIONS: An estimated 3.7 million US adults had hyperkalemia in 2014, and this prevalence rate has increased since 2010. In patients with CKD and/or heart failure, the annual prevalence of hyperkalemia was 6.35% in 2014, and about half of all patients with hyperkalemia have either CKD and/or heart failure.

PCSK9 Loss-of-Function Variants, Low-Density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From 9 Studies of Blacks and Whites.

BACKGROUND: PCSK9 loss-of-function (LOF) variants allow for the examination of the effects of lifetime reduced low-density lipoprotein cholesterol (LDL-C) on cardiovascular events. We examined the association of PCSK9 LOF variants with LDL-C and incident coronary heart disease and stroke through a meta-analysis of data from 8 observational cohorts and 1 randomized trial of statin therapy. METHODS AND RESULTS: These 9 studies together included 17 459 blacks with 403 (2.3%) having at least 1 Y142X or C679X variant and 31 306 whites with 955 (3.1%) having at least 1 R46L variant. Unadjusted odds ratios for associations between PCSK9 LOF variants and incident coronary heart disease (851 events in blacks and 2662 events in whites) and stroke (523 events in blacks and 1660 events in whites) were calculated using pooled Mantel-Haenszel estimates with continuity correction factors. Pooling results across studies using fixed-effects inverse-variance-weighted models, PCSK9 LOF variants were associated with 35 mg/dL (95% confidence interval [CI], 32-39) lower LDL-C in blacks and 13 mg/dL (95% CI, 11-16) lower LDL-C in whites. PCSK9 LOF variants were associated with a pooled odds ratio for coronary heart disease of 0.51 (95% CI, 0.28-0.92) in blacks and 0.82 (95% CI, 0.63-1.06) in whites. PCSK9 LOF variants were not associated with incident stroke (odds ratio, 0.84; 95% CI, 0.48-1.47 in blacks and odds ratio, 1.06; 95% CI, 0.80-1.41 in whites). CONCLUSIONS: PCSK9 LOF variants were associated with lower LDL-C and coronary heart disease incidence. PCSK9 LOF variants were not associated with stroke risk.

The Clinical and Economic Burden of Hyperkalemia on Medicare and Commercial Payers.

BACKGROUND: Hyperkalemia (serum potassium >5.0 mEq/L) may be caused by reduced kidney function and drugs affecting the renin-angiotensin-aldosterone system and is often present in patients with chronic kidney disease (CKD). OBJECTIVE: To quantify the burden of hyperkalemia in US Medicare fee-for-service and commercially insured populations using real-world claims data, focusing on prevalence, comorbidities, mortality, medical utilization, and cost. METHODS: A descriptive, retrospective claims data analysis was performed on patients with hyperkalemia using the 2014 Medicare 5% sample and the 2014 Truven Health Analytics MarketScan Commercial Claims and Encounter databases. The starting study samples required patient insurance eligibility during ≥1 months in 2014. The identification of hyperkalemia and other comorbidities required having ≥1 qualifying claims in 2014 with an appropriate International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code in any position. To address the differences between patients with and without hyperkalemia, CKD subsamples were analyzed separately. Mortality rates were calculated in the Medicare sample population only. The claims were grouped into major service categories; the allowed costs reflected all costs incurred by each cohort divided by the total number of member months for that cohort. RESULTS: The prevalence of hyperkalemia in the Medicare and commercially insured samples was 2.3% and 0.09%, respectively. Hyperkalemia was associated with multiple comorbidities, most notably CKD. The prevalence of CKD in the Medicare and the commercially insured members with hyperkalemia was 64.8% and 31.8%, respectively. After adjusting for CKD severity, the annual mortality rate for Medicare patients with CKD and hyperkalemia was 24.9% versus 10.4% in patients with CKD without hyperkalemia. The allowed costs in patients with CKD and hyperkalemia in the Medicare and commercially insured cohorts were more than twice those in patients with CKD without hyperkalemia. Inpatient care accounted for >50% of costs in patients with CKD and hyperkalemia. CONCLUSION: Hyperkalemia is associated with substantial clinical and economic burden among US commercially insured and Medicare populations.

Migraine Prophylaxis and Acute Treatment Patterns Among Commercially Insured Patients in the United States.

OBJECTIVES: To describe prophylactic and acute medication treatment patterns, including timing, medication type, and duration of use in migraine patients initiating prophylaxis. BACKGROUND: Patients with migraine can be treated with acute and prophylactic therapies. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adherence and persistence. METHODS: This retrospective cohort study used the Truven Health Analytics MarketScan® Research Databases to identify adults in the United States with a migraine diagnosis who initiated migraine prophylactic medication (index event) between January 1, 2008, and December 31, 2011. Prescribed prophylactic medications evaluated included topiramate, beta-blockers, and tricyclic antidepressants. Patients were required to have 12 months of pre- and post-index continuous enrollment. Patient characteristics, migraine-specific prescribed prophylactic treatment patterns (including gaps in therapy, treatment switches, and additions of index medications), and prescribed acute medication utilization were assessed. RESULTS: The study population comprised 107,122 patients, with 52,275 (49%) initiating topiramate, 22,658 (21%) initiating beta-blockers, and 32,189 (30%) initiating tricyclic antidepressants. Mean (SD) age was 41 (12) years and 83% were female. Persistence with migraine prophylactic medication was low; 81% of patients had gaps of >90 days in their migraine prophylaxis in the first year. The gap in therapy occurred early in treatment (mean, 95 days), and only 10% of patients restarted prophylactic therapy within that year. Switching from index medication to another prophylactic medication or adding prophylaxis was uncommon (13% and 5%, respectively). One year after initiating prophylaxis, 65% of patients were not receiving any prophylactic therapies. Most patients initiating migraine prophylaxis also utilized acute treatments (81%); opioid use was more frequent than triptan use (53% vs 48%) and was common (40%) among patients without other chronic pain conditions (eg, arthritis, fibromyalgia, and lower back pain). CONCLUSION: Patients with migraine who initiated prophylactic therapy had poor persistence with early gaps in therapy, were unlikely to switch prophylactic treatments, and most discontinued prophylaxis by the end of the first year.

Towards coherent data policy for biomedical research with ELSI 2.0: orchestrating ethical, legal and social strategies.

As the recent inaugural Ethical, Legal, and Social Issues (ELSI) 2.0 conference made clear, the effects of information communication technology (ICT) are pervasive in biomedical research. Data initiatives are arising in all corners of biomedicine. Data sharing efforts already promised to surpass even the ambitious goals of the National Human Genome Research Institute, only 5 years after publication of its 10-year vision. ELSI research was established, in part, to address challenges of open data access and data sharing. However, by and large, ELSI research projects address particular concerns of a given population, jurisdiction, type of research practice or type of data. This does not necessarily facilitate coherent data policy for sustainable data stewardship. Forward-looking, data friendly strategies need to be considered. Orchestration strategies are needed which overcome barriers to collective action. Here we present challenges policymakers face, and suggest three basics steps towards meeting them. First, policymakers must recognise the systematic change that occurs when ICT enables dataflow itself to become an organising principle of biomedical research. Second, methods for identifying and gathering types of metadata suitable for ELSI research ought to be developed and regulated. Third, policymakers need to organise in ways that mirror the new vision for data-enabled research that data technologies are making possible, as ELSI 2.0 encourages researchers to do. Taking these steps will help ensure research evolves in ways that warrants trust of the public while still supporting widespread ethical access to necessary data, research subjects, samples and findings.

Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls.

BACKGROUND: Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. METHOD: We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). RESULTS: While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = -2.33, p = 0.02) and at trend level in healthy controls (Z = -1.87, p = 0.06). CONCLUSIONS: These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

The impact of CACNA1C gene, and its epistasis with ZNF804A, on white matter microstructure in health, schizophrenia and bipolar disorder1.

Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health. 230 individuals (with existing ZNF804A rs1344706 genotype data) were genotyped for CACNA1C rs1006737 and underwent DTI. FA data was analysed with tract-based spatial statistics and threshold-free cluster enhancement significance correction (P < 0.05) to detect effects of CACNA1C genotype on FA, and its potential interaction with ZNF804A genotype and with diagnosis, on FA. There was no significant main effect of the CACNA1C genotype on FA, nor diagnosis by genotype(s) interactions. Nevertheless, when inspecting SZ in particular, risk allele carriers had significantly lower FA than the protective genotype individuals, in portions of the left middle occipital and parahippocampal gyri, right cerebellum, left optic radiation and left inferior and superior temporal gyri. Our data suggests a minor involvement of CACNA1C rs1006737 in psychosis via conferring susceptibility to white matter microstructural abnormalities in SZ. Put in perspective, ZNF804A rs1344706, not only had a significant main effect, but its SZ-specific effects were two orders of magnitude more widespread than that of CACNA1C rs1006737.

Armored Scales and Their Parasitoids on Commercial Avocados Grown in California or Imported from Mexico.

Levels of armored scales (Hemiptera: Diaspididae) on Mexican Hass avocados imported into California over May 2008-June 2009 were monitored on 135 trucks entering the state via the Blythe border station, the entry point receiving the highest volume of fruit. Levels of live sessile scales were 3.9-fold higher than indicated in a previous survey (September 2007-April 2008) although levels of live eggs and crawlers were similar to previous levels. A survey of avocado fruit in California infested with armored scales detected four species known to be endemic but failed to find any of the seven exotic Diaspididae entering the state on Mexican fruit. Monitoring of Mexican armored scales on imported avocados from September 2007 to December 2010 recovered 10 species of parasitoids predominated by two species of Signiphora Ashmead (Hymenoptera: Signiphoridae). One of these species, Signiphora flavopalliata Ashmead, comprised 36% of all collected Mexican parasitoids and is a known hyperparasitoid. A survey of armored scale parasitoids present on commercial California avocados detected 17 genetic signatures, with only four of these in common with those detected on imported Mexican fruit. The implications of these findings are discussed.

Citizen science or scientific citizenship? Disentangling the uses of public engagement rhetoric in national research initiatives.

BACKGROUND: The language of "participant-driven research," "crowdsourcing" and "citizen science" is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists. Originally, these labels were invoked by volunteer research efforts propelled by amateurs outside of traditional research institutions and aimed at appealing to those looking for more "democratic," "patient-centric," or "lay" alternatives to the professional science establishment. As mainstream translational biomedical research requires increasingly larger participant pools, however, corporate, academic and governmental research programs are embracing this populist rhetoric to encourage wider public participation. DISCUSSION: We examine the ethical and social implications of this recruitment strategy. We begin by surveying examples of "citizen science" outside of biomedicine, as paradigmatic of the aspirations this democratizing rhetoric was originally meant to embody. Next, we discuss the ways these aspirations become articulated in the biomedical context, with a view to drawing out the multiple and potentially conflicting meanings of "public engagement" when citizens are also the subjects of the science. We then illustrate two uses of public engagement rhetoric to gain public support for national biomedical research efforts: its post-hoc use in the "care.data" project of the National Health Service in England, and its proactive uses in the "Precision Medicine Initiative" of the United States White House. These examples will serve as the basis for a normative analysis, discussing the potential ethical and social ramifications of this rhetoric. We pay particular attention to the implications of government strategies that cultivate the idea that members of the public have a civic duty to participate in government-sponsored research initiatives. We argue that such initiatives should draw from policy frameworks that support normative analysis of the role of citizenry. And, we conclude it is imperative to make visible and clear the full spectrum of meanings of "citizen science," the contexts in which it is used, and its demands with respect to participation, engagement, and governance.

LDL cholesterol response and statin adherence among high-risk patients initiating treatment.

OBJECTIVES: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol treatment guideline recommends monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. We examined LDL-C reduction and statin adherence among high-risk patients initiating statins in a real-world setting. STUDY DESIGN: Retrospective cohort study. METHODS: The study population included Kaiser Permanente Georgia members (n = 1066) with a history of coronary heart disease or risk equivalent(s) initiating statins in 2011. Percent change in LDL-C was defined using measurements before and 60 to 450 days after statin initiation. Statin adherence was defined by proportion of days covered, categorized as high (≥80%), intermediate (50%-79%), and low (< 50%). RESULTS: Overall, 58.4% of patients failed to achieve a ≥ 30% LDL-C reduction after statin initiation. The prevalences of high, intermediate, and low statin adherence were 41.3%, 23.2%, and 35.6%, respectively. Of patients with high adherence, 42.3% did not achieve a ≥ 30% reduction in LDL-C compared with 54.7% and 79.7% of those with intermediate and low statin adherence, respectively. After multivariable adjustment, and compared with those with high adherence, the risk ratios for not achieving a ≥ 30% LDL-C reduction were 1.31 (95% CI, 1.13-1.52) and 1.88 (95% CI, 1.67-2.11), for those with intermediate and low adherence. Women and African Americans were less likely to have high adherence, whereas having cardiologist visits was associated with high adherence. CONCLUSIONS: In a real-world setting, many patients did not achieve a 30% or larger LDL-C reduction. These data support the ACC/AHA recommendation to monitor LDL-C response among patients initiating statins.

Characterizing the severe asthma population in the United States: claims-based analysis of three treatment cohorts in the year prior to treatment escalation.

OBJECTIVES: Little is known about the disposition of severe patients prior to treatment escalation. To classify patients by treatment step using pharmacy data and describe their economic and healthcare utilization, insurance status, and sociodemographic characteristics in the year prior to escalation to Global Initiative for Asthma (GINA) steps 4 and 5. METHODS: This was a retrospective claims cohort study of asthma patients (age 12-75 years) newly initiated on "stable therapy" (three consecutive months of therapy) with omalizumab, high intensity corticosteroids (HICS; ≥1000 µg/d inhaled fluticasone equivalent or oral prednisone), or high-dose inhaled corticosteroid (HDICS; ≥500-<1000 µg/d fluticasone equivalent) from 2002 to 2011. Other asthma treatments were compared as a reference. RESULTS: Of 25,297 patients, 856 initiated omalizumab, 6926 initiated HICS, and 11,445 initiated HDICS. In the year prior to treatment escalation to omalizumab, HICS, and HDICS, respectively, individuals had high annual mean medical expenditures ($14,071, $12,030, and $7570), utilization (27 outpatient and 10 specialty care visits; 19 outpatient and three specialty; 15 outpatient and two specialty), asthma-related prescription drugs (11.74, 7.8, and 5.17) and chronic comorbidities (2.68, 2.67, and 2.19). Prior to omalizumab treatment, patients were more likely to be salaried, full-time employees with commercial PPO/POS insurance. CONCLUSIONS: Prior to escalating treatment to GINA steps 4 and 5, individuals experienced significant annual medical expenditures, healthcare resource utilization and polypharmacy burden, which may reflect poorly controlled asthma and the need to escalate treatment. Medical claims data and utilization-based measures may be helpful in classifying individuals by GINA treatment step.

INPP4B overexpression is associated with poor clinical outcome and therapy resistance in acute myeloid leukemia.

In this study, we investigated the role of inositol polyphosphate-4-phosphatase, type-II (INPP4B) in acute myeloid leukemia (AML). We observed that AML patients with high levels of INPP4B (INPP4B(high)) had poor response to induction therapy, shorter event-free survival and shorter overall survival. Multivariate analyses demonstrated that INPP4B(high) was an independent predictor of poor prognosis, significantly improving current predictive models, where it outperformed conventional biomarkers including FLT3-ITD and NPM1. Furthermore, INPP4B(high) effectively segregated relative risk in AML patients with normal cytogenetics. The role of INPP4B on the biology of leukemic cells was assessed in vitro. Overexpression of INPP4B in AML cell lines enhanced colony formation potential, recapitulated the chemotherapy resistance observed in AML patients and promoted proliferation in a phosphatase-dependent, and Akt-independent manner. These findings reveal that INPP4B(high) has an unexpected role consistent with oncogenesis in AML, in contrast to its previously reported tumor-suppressive role in epithelial cancers. Overall, we propose that INPP4B is a novel prognostic biomarker in AML that has potential to be translated into clinical practice both as a disease marker and therapeutic target.