A rapid and robust tri-color flow cytometry assay for monitoring malaria parasite development

Microscopic examination of Giemsa-stained thin blood smears remains the gold standard method used to quantify and stage malaria parasites. However, this technique is tedious, and requires trained microscopists. We have developed a fast and simple flow cytometry method to quantify and stage, various malaria parasites in red blood cells in whole blood or in vitro cultured Plasmodium falciparum. The parasites were stained with dihydroethidium and Hoechst 33342 or SYBR Green I and leukocytes were identified with an antibody against CD45. Depending on the DNA stains used, samples were analyzed using different models of flow cytometers. This protocol, which does not require any washing steps, allows infected red blood cells to be distinguished from leukocytes, as well as allowing non-infected reticulocytes and normocytes to be identified. It also allows assessing the proportion of parasites at different developmental stages. Lastly, we demonstrate how this technique can be applied to antimalarial drug testing

Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. METHODS: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. FINDINGS: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5–3·0) of age-standardised female deaths and 6·8% (5·8–8·0) of age-standardised male deaths. Among the population aged 15–49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2–4·3) of female deaths and 12·2% (10·8–13·6) of male deaths attributable to alcohol use. For the population aged 15–49 years, female attributable DALYs were 2·3% (95% UI 2·0–2·6) and male attributable DALYs were 8·9% (7·8–9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0–1·7] of total deaths), road injuries (1·2% [0·7–1·9]), and self-harm (1·1% [0·6–1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2–33·3) of total alcohol-attributable female deaths and 18·9% (15·3–22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week. INTERPRETATION: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption. FUNDING: Bill & Melinda Gates Foundation

CPE Hepatitis C therapy: Looking toward interferon-sparing regimens

Abstract Objective: To describe chronic hepatitis C virus (HCV) infection, including its epidemiology and pathophysiology; review current treatment options for HCV infection; recognize investigational agents being studied as part of interferon-free therapy; and summarize clinical trials for the new agents. Data sources: PubMed for 2004 through August 2014 using search terms hepatitis C, American Association for the Study of Liver Diseases, sofosbuvir, simeprevir, and as needed specific names of other agents in development during this time; news articles and news releases about company actions with regard to clinical trials and filings for marketing approval in the United States. Study selection: At the discretion of the author based on clinical relevance of study and relevance to national guidelines for HCV therapy. Results: HCV infection is an important medical and public health problem in the United States and worldwide that can cause cirrhosis, hepatocellular carcinoma, and liver failure. The advent of newly developed targeted therapies is changing the treatment paradigm for this disease. Although traditional therapy with pegylated interferon and ribavirin remain therapeutic options, direct-acting agents such as sofosbuvir (Sovaldi-Gilead) and simeprevir (Olysio-Janssen) are producing faster, earlier, and improved treatment response with fewer adverse effects. The combination of anti-HCV agents and the duration of treatment are based on genotype, patient treatment status, and patient risk factors. The dramatic and sustained clearance of the virus with these drugs makes sustained virologic response a reality for patients who are unable to tolerate pegylated interferon. The downside is their high cost, which may make them economically unsustainable. However, for patients infected with HCV, the potential for a cure and improved quality of life may now be a reality. Conclusion: HCV, a well-known blood-borne disease associated with significant morbidity and mortality worldwide, can be effectively and safely treated with new anti-HCV agents such as SOF. While these new medications are in their early days of real-world practice, they offer hope that cure is truly possible. Learning objectives At the conclusion of this knowledge-based activity, the pharmacist will be able to: ■ Describe chronic hepatitis C virus (HCV) infection, including its epidemiology and pathophysiology. ■ Review current treatment options for HCV infection. ■ Recognize investigational agents being studied as part of interferon-free therapy. ■ Summarize clinical trials for the new agents. There is no fee associated with this activity for members of the American Pharmacists Association. There is a $25 fee for nonmembers. Accreditation informatio

Evaluation of the relevance and access of EHR-based variables to support personalized medicine in breast cancer

Background: The increasing number of available cancer therapies render medical decision-making (MDM) less straightforward. Patients want to know about the outcomes of similarly treated patients. Objective: The goal of this study was to design a breast cancer dashboard (BCD) tool that presents survival information to support MDM activities. Methods: Clinical variables during the clinic visit were determined via provider meetings and evaluated for accessibility from medical databases. Women with breast cancer (BC) were interviewed about their health care experiences after cancer diagnosis. We created a cohort of BC adult women treated at our institution from 1995 to 2012, from which clinical scenarios were defined and used to test survival outcomes. For the BCD, a simple, graphical user interface was built to present point-of-care clinical and survival data. Results: It is feasible to build the BCD using our institution’s databases and generate survival plots to facilitate MDM activities. Patients with early-stage BC had the highest survival rate (82.3%) and the longest mean life years of 7.0 (SD 4.5) years. In late-stage BC, poor prognosis outweighs the influence of number of comorbidities on mortality. The BCD tool promotes more predictive, personalized, and collaborative health care

Program in Personalized Health Care

Abstract: Background: The increasing number of available cancer therapies render medical decision-making (MDM) less straightforward. Patients want to know about the outcomes of similarly treated patients. Objective: The goal of this study was to design a breast cancer dashboard (BCD) tool that presents survival information to support MDM activities. Methods: Clinical variables during the clinic visit were determined via provider meetings and evaluated for accessibility from medical databases. Women with breast cancer (BC) were interviewed about their health care experiences after cancer diagnosis. We created a cohort of BC adult women treated at our institution from 1995 to 2012, from which clinical scenarios were defined and used to test survival outcomes. For the BCD, a simple, graphical user interface was built to present point-of-care clinical and survival data. Results: It is feasible to build the BCD using our institution's databases and generate survival plots to facilitate MDM activities. Patients with early-stage BC had the highest survival rate (82.3%) and the longest mean life years of 7.0 (SD 4.5) years. In late-stage BC, poor prognosis outweighs the influence of number of comorbidities on mortality. The BCD tool promotes more predictive, personalized, and collaborative health care. ABOUT THE AUTHORS The authors work across the University of Utah Health Sciences in oncology clinical practice, bioinformatics, and pharmacotherapy outcomes research. Our work is aimed at improving patient care via outcomes research and assessment. The Center's personnel have expertise in health economics, modeling, various clinical subspecialties (including oncology), drug information, statistical analysis and programming, and database management. PUBLIC INTEREST STATEMENT As more breast cancer treatment options become available, the shared medical decision-making relationship between physician and patient is becoming less straightforward. To support this important interaction, we have created an institution-specific medical communication tool. Decision aids have been shown to improve the health care experience of patients and ultimately lead to the achievement of higher-quality decisions. Our communication tool, named the breast cancer dashboard (BCD), was designed to be used during the clinic visit. It specifically address patients' needs to know about the survival outcomes of similar patients treated at our cancer specialty hospital. The BCD brings together comprehensive and breast cancerspecific clinical information. It allows both the provider and patient to navigate the information using a patient-friendly graphic interface. By enhancing shared decision-making, there would be a shift toward patient care that is more predictive, preventive, personalized, and collaborative

Predictive genomic markers of response to VEGF targeted therapy in metastatic renal cell carcinoma.

BACKGROUND:First-line treatment for metastatic renal cell carcinoma (mRCC) is rapidly changing. It currently includes VEGF targeted therapies (TT), multi-target tyrosine kinase inhibitors (TKIs), mTOR inhibitors, and immunotherapy. To optimize outcomes for individual patients, genomic markers of response to therapy are needed. Here, we aim to identify tumor-based genomic markers of response to VEGF TT to optimize treatment selection. METHODS:From an institutional database, primary tumor tissue was obtained from 79 patients with clear cell mRCC, and targeted sequencing was performed. Clinical outcomes were obtained retrospectively. Progression-free survival (PFS) on first-line VEGF TT was correlated to genomic alterations (GAs) using Kaplan-Meier methodology and Cox proportional hazard models. A composite model of significant GAs predicting PFS in the first-line setting was developed. RESULTS:Absence of VHL mutation was associated with inferior PFS on first-line VEGF TT. A trend for inferior PFS was observed with GAs in TP53 and FLT1 C/C variant. A composite model of these 3 GAs was associated with inferior PFS in a dose-dependent manner. CONCLUSION:In mRCC, a composite model of TP53 mutation, wild type VHL, and FLT1 C/C variant strongly predicted PFS on first-line VEGF TT in a dose-dependent manner. These findings require external validation

Caregiver burden by treatment and clinical characteristics of patients with glioblastoma.

BackgroundGlioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).MethodsCaregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.ResultsThe final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.ConclusionThis study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience