Hemophagocytic lymphohistiocytosis/cytokine release syndrome secondary to neoadjuvant pembrolizumab for triple-negative breast cancer: a case study

As indications for immune checkpoint inhibitors for breast cancer continue to expand, rare toxicities will emerge that require careful consideration and multidisciplinary management. We report the case of a 40-year-old female receiving neoadjuvant pembrolizumab and chemotherapy for locally advanced triple-negative breast cancer who developed cytokine release syndrome (CRS)/hemophagocytic lymphohistiocytosis (HLH). CRS/HLH secondary to pembrolizumab are scarcely documented in the literature and, to our knowledge, have never been reported in the context of neoadjuvant treatment for breast cancer

Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : a novel analysis from the Global Burden of Disease Study 2015

Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r= 0.88), an index of 11 universal health coverage interventions (r= 0.83), and human resources for health per 1000 (r= 0.77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28.6 to 94.6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40.7 (95% uncertainty interval, 39.0-42.8) in 1990 to 53.7 (52.2-55.4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21.2 in 1990 to 20.1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73.8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-systemcharacteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Nutrition-related practices and attitudes of Kansas skipped-generation(s) caregivers and their grandchildren

Despite growing numbers, the nutrition practices and attitudes of skipped generation(s) kinship caregivers regarding feeding the dependent children in their care have not been examined. In this qualitative study, transcriptions of semi-structured interviews with 19 female and four male skipped-generation(s) Kansas caregivers (ages 47 to 80, 92% non-Hispanic whites, 83% female, 78% grandparents and 22% great-aunt or great grandparent caregivers; caring for a range of one to four children, ages three to 18, for an average of nine years) were content analyzed for how their nutrition-related practices and attitudes had changed since parenting the first time. Sub-themes regarding practices included: being more nutrition and food safety conscious now, and shifting their child feeding style. The children seemed to be adversely affected by an on-the-go lifestyle and the use of more electronics. Caregivers described their sources for child feeding advice as being based mostly on information from their mothers, physicians, and their past parenting experiences. Sub-themes for attitudes included opinions that nutrition and safe food handling are important and that nutritious food is expensive. They preferred printed or video nutrition education materials and wanted to receive information through organizations they trusted. This population could benefit from education on: infant, child, adolescent, and sports nutrition; feeding “picky eaters”; healthful recipes, “fast foods” and packaged foods; quick, inexpensive meals and snacks low in fat, sugar, and salt; limiting sedentary time; family meals; using food thermometers; and intergenerational gardening and cooking

Dear Friend: Letters from Elizabeth Ott to Alton Easton

This is the culmination of a class project created by students in Dr. Elizabeth Fleitz\u27s English 36500: Digital Humanities course during Fall semester 2020. This site collects the letters of Elizabeth Ott, Lindenwood College teacher, written to her fiancé Alton Easton, in 1847-1848. Her letters are long, chatty, and give insight on people and events in the St. Charles area at the time, as well as illuminate the personality of Ott herself. We have transcribed each of these letters, and briefly summarize and annotate them to guide the reader in their exploration

Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role

Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68.Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), frequently preceded by respiratory disease. A cluster of 11 suspect cases of pediatric AFM was identified in September 2016 in Phoenix, AZ. To determine if these cases were associated with EV-D68, we performed multiple genomic analyses of nasopharyngeal (NP) swabs and cerebrospinal fluid (CSF) material from the patients, including real-time PCR and amplicon sequencing targeting the EV-D68 VP1 gene and unbiased microbiome and metagenomic sequencing. Four of the 11 patients were classified as confirmed cases of AFM, and an additional case was classified as probable AFM. Real-time PCR and amplicon sequencing detected EV-D68 virus RNA in the three AFM patients from which NP swabs were collected, as well as in a fourth patient diagnosed with acute disseminated encephalomyelitis, a disease that commonly follows bacterial or viral infections, including enterovirus. No other obvious etiological causes for AFM were identified by 16S or RNA and DNA metagenomic sequencing in these cases, strengthening the likelihood that EV-D68 is an etiological factor. Herpes simplex viral DNA was detected in the CSF of the fourth case of AFM and in one additional suspect case from the cluster. Multiple genomic techniques, such as those described here, can be used to diagnose patients with suspected EV-D68 respiratory illness, to aid in AFM diagnosis, and for future EV-D68 surveillance and epidemiology

Altered developmental trajectories for impulsivity and sensation seeking among adolescent substance users

A number of studies have associated impulsivity and sensation seeking with level of substance use and risk for developing a substance use disorder. These relationships may be particularly apparent during adolescence, when developmental changes in impulsivity and sensation seeking occur at the same time as increased opportunities for substance use. To examine this, the current study measured impulsivity and sensation seeking from pre-adolescence to mid-adolescence in a sample of youth, the majority of whom were identified as being at risk for developing a substance use disorder based on their family history of substance use disorders. Youth were separated into those who did (n = 117) and did not (n = 269) initiate substance use by mid-adolescence. Results showed that substance users were more impulsive and more sensation seeking during pre-adolescence, prior to any significant substance use, and that greater sensation seeking in pre-adolescence was related to heavier substance use by mid-adolescence. In addition, developmental trajectories for substance-using youth showed a greater increase in sensation seeking but a more modest decrease in impulsivity from pre-adolescence to mid-adolescence. Taken together, these results indicate that increased impulsivity and sensation seeking is apparent in adolescent substance users as early as pre-adolescence, that the difference between substance users and non-users becomes larger across early adolescence as their developmental trajectories diverge, and that greater sensation seeking in pre-adolescence may predict increased substance use by mid-adolescence