Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness.

Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Sleep plays an important role in the regulation of central nervous system and body physiologic functions. Sleep architecture changes with age and is easily susceptible to external and internal disruption. Reduction or disruption of sleep can affect numerous functions varying from thermoregulation to learning and memory during the waking state.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Consumption of Dry Beans, Peas, and Lentils Could Improve Diet Quality in the US Population

The US Department of Agriculture's MyPyramid guidelines introduced a near doubling of the dietary recommendations for vegetables. These recommendations target specific subgroups of vegetables, including dry beans and peas. Dry beans and peas provide an array of nutrients and phytochemicals that have been shown to have beneficial health effects, yet consumption levels in the United States are quite low. Few studies have examined the influence of legume consumption on nutrient intakes. Therefore, the purpose of this study was to assess nutrient and food group intakes of dry bean and pea consumers compared to nonconsumers. Dietary intake data from the 1999-2002 National Health and Nutrition Examination Survey for adults aged ≥19 years was used. Results show that on any given day only 7.9% of adults are consuming dry beans and peas; Mexican Americans or other Hispanics are more likely to be consumers than nonconsumers. Consuming approximately ½ c dry beans or peas resulted in higher intakes of fiber, protein, folate, zinc, iron, and magnesium with lower intakes of saturated fat and total fat. These data support the specific recommendation for dry beans and peas as part of the overall vegetable recommendation. Increased consumption of dry beans and peas—economical and nutrient-rich foods—could improve the diet quality of Americans.     

Americans' Awareness, Knowledge, and Behaviors Regarding Fats: 2006-2007

In recent years, epidemiologic and clinical studies, public and regulatory policy activity, and media coverage have focused on issues related to trans fats. To help increase awareness and understanding of trans fats and other fats, the American Heart Association (AHA) launched the “Face the Fats” national consumer education campaign in April 2007. The AHA commissioned a quantitative tracking survey between 2006 and 2007 to measure changes in consumer awareness, knowledge, and behaviors related fats and oils and their perceived impact on heart disease. The survey was conducted by Cogent Research. Data were collected during March 2006 and May 2007. At both time points, the survey included a representative sample of the American population age 18 to 65 years (n=1,000). The sampling plan for the survey was designed based on the 2000 and 2003 US Census. The margin of error was ±3.10 percentage points. Awareness of trans fats increased during the 1-year study period. In 2007, 92% of respondents were aware of trans fats, an increase from 84% in 2006 (P<0.05). The 2007 level was similar to the awareness of saturated fats (93%). Perceptions that certain fats and oils heighten the risk of heart disease increased for trans fats (73% in 2007 vs 63% in 2006; P<0.05), saturated fats (77% in 2007 vs 73% in 2006; P<0.05), and partially hydrogenated oils (56% in 2007 vs 49% in 2006; P<0.05). Knowledge about food sources of different fats remained low. On an unaided basis, 21% could name three food sources of trans fats in 2007, up from 17% in 2006 (P<0.05). Knowledge of food sources of saturated fat remained unchanged at 30% in 2007. Significantly more respondents in 2007 reported behavioral changes related to trans fat information, such as buying food products because they show “zero trans fat” on labels or packages (37% in 2007 vs. 32% in 2006; P<0.05). Between 2006 and 2007, consumer awareness about trans fats increased and attained awareness levels similar to saturated fats. The increased awareness is associated with improved self-reported behaviors in grocery shopping. Nonetheless, overall knowledge, especially regarding food sources of saturated and trans fats, remains relatively low, underscoring the need for heightened consumer education activities. The positive change in consumer awareness about trans fats is likely attributable to the wide range of messages available to them, including the AHA “Face the Fats” national consumer education campaign.     

Publishing Nutrition Research: A Review of Epidemiologic Methods

The use of epidemiologic research designs and analytical methods is common in dietetics research. Food and nutrition professionals who seek to perform evidence-based practice or participate in research design, analysis, and communication need skills in the essentials of epidemiology. This is one of a series of monographs on research methodology that addresses these needs and supports the goals of the Board of Editors of the Journal of the American Dietetic Association to further enhance competency and skills. This monograph focuses on statistical approaches for univariate analyses used with the primary observational study designs associated with epidemiology. Tables illustrating the presentation and interpretation of these results are included.     

Grandmothers, Fathers, and Depressive Symptoms Are Associated with Food Insecurity among Low-Income First-Time African-American Mothers in North Carolina

African Americans experience household food insecurity, ie, the limited availability of nutritionally adequate and safe food, or ability to acquire acceptable foods in socially acceptable ways, at three times the rate of non-Hispanic whites. Thirty percent of all African-American children live in food-insecure households. The purpose of this study was to identify characteristics associated with household food insecurity among a high-risk postpartum population. Two-hundred six low-income, African-American mother−infant dyads were recruited through the Special Supplemental Nutrition Program for Women, Infants, and Children clinics. The six-item US Department of Agriculture food security scale was used to classify households as food secure, marginally food secure, or food insecure. Multinomial logistic regression was used to estimate the association between selected maternal/household characteristics and household food-security status. Fifty-three percent of households were food secure, 34% were marginally food secure, and 13% were food insecure. Maternal education less than college (relative risk ratio [RRR]=0.46; 95% confidence interval [CI]: 0.22 to 0.98) was inversely associated with marginal food security. Depressive symptoms (RRR=1.09; 95% CI: 1.02 to 1.16) and having the baby's father in the household (RRR=3.46; 95% CI: 1.22 to 9.82) were associated with household food insecurity, while having a grandmother in the household (RRR=0.15; 95% CI: 0.03 to 0.80) was inversely associated with experiencing household food insecurity. Findings from this study suggest that young, low-income, African-American families with only one child are particularly susceptible to experiencing household food insecurity. Intergenerational support and transfer of knowledge can be a key protective attribute among low-income African-American households.