A Helping Hand Out of the River: Refugee Perspectives for Provider Engagement.

Purpose: A growing number of refugee groups are seeking care within the U.S. health care system for medical, psychological, and social needs. Research is limited in understanding refugee-specific conceptualizations of helping relationships and provider characteristics that improve interactions in health systems. This study aimed to identify provider characteristics that facilitate engagement and helpfulness in a refugee-specific population from refugee participant voices to inform future practices of health care clinics. Methods: Semi-structured interviews with refugee participants were conducted to assess 1) experiences moving on from difficult experiences, 2) engagement with the health system, and 3) provider characteristics that facilitated engagement and healing. Qualitative data were analyzed using a grounded theory approach. Results: An emergent theory was revealed on refugee-defined provider characteristics that facilitated healing and engagement in the health system. Providers who support an individual's story to be told, show awareness of barriers to accessing resources and prioritization of addressing barriers, maintain cultural humility, and demonstrate compassion, empathy, warmth, and openness toward patient engagement were the primary characteristics that facilitated engagement and healing. Conclusions: Utilization of engagement strategies by providers at the onset of treatment is critical to providing culturally sensitive health care. Nonspecific but essential provider characteristics are thought to improve relational dynamics, trust-building, and overall engagement in the U.S. health care system from the perspective of refugee participants.

"A Shell of My Former Self": Using Figurative Language to Promote Communication About Patient Suffering.

While the relief of suffering is an important goal of medicine, suffering is often missed or ignored in clinical practice. We believe that this occurs for two reasons. First, clinicians often approach suffering by focusing on the causes of suffering rather than the experience of suffering. Second, the subjective nature of suffering makes it difficult to discuss. To address these gaps, we read 52 relevant works of literature and performed qualitative analysis to categorize figurative language into themes of psychological (i.e., non-physical) suffering. We identified 254 excerpts of figurative language characterizing psychological suffering. Among these excerpts, 13 salient themes recurred, including: brokenness, diminishment, disorientation, drowning, emptiness, imprisonment, battle, darkness, isolation, invisibility, lifelessness, punishment, and torture. The development of a shared language of suffering can foster a therapeutic patient-clinician relationship and improve clinicians' ability to recognize and address a patient's experience of suffering.

Rheumatic Heart Disease in the United States: Forgotten But Not Gone: Results of a 10 Year Multicenter Review.

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non-White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08-1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline-based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Previous Traditional Medicine Use for Sore Throat among Children Evaluated for Rheumatic Fever in Northern Uganda.

Timely diagnosis of group A streptococcal (GAS) sore throat coupled with appropriate antibiotic treatment is necessary to prevent serious post-streptococcal complications, including rheumatic fever (RF) and rheumatic heart disease (RHD). Traditional medicine (TM) is a known common adjunct to formal medical care in sub-Saharan Africa. A better understanding of health-seeking behavior for sore throat both within and outside the formal medical system is critical to improving primary prevention efforts of RF and RHD. A prospective mixed-methods study on the use of TM for sore throat was embedded within a larger epidemiological study of RF in Northern Uganda. Children presenting with symptoms of RF were interviewed about recent TM use as well as health services use for sore throat. One hundred children with a median age of 10 years (interquartile range: 6.8-13 years) completed the TM interview with their parent/guardian as part of a research study of RF. Seventeen, or 17%, accessed a TM provider for sore throat as part of the current illness, and 70% accessed TM for sore throat in the past (73% current or past use). Of the 20 parents who witnessed the TM visit, 100% reported use of crude tonsillectomy. Penicillin was the most frequently prescribed medication by TM providers in 52% of participants who were seen by a TM provider. The use of TM among children presenting with symptoms of sore throat in northern Uganda is common and frequently used in tandem with diagnostic services offered through the formal healthcare system. Engagement with TM practitioners may provide an important avenue for designing effective primary prevention and management strategies of RF and reduce the global burden of RHD.

Active Case Finding for Rheumatic Fever in an Endemic Country.

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.

Cross-sectional study of population-specific streptococcal antibody titres in Uganda.

OBJECTIVE: Despite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda. DESIGN: This was an observational cross-sectional study. SETTING: This study was conducted at Mulago National Referral Hospital, which is located in the capital city, Kampala, and includes the Uganda Heart Institute. PATIENTS: Participants (aged 0-50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5-15 years. MAIN OUTCOME MEASURES: ASO was measured in-country by nephelometric technique. ADB samples were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established. RESULTS: The median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL. CONCLUSIONS: The estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.

Changing How Race Is Portrayed in Medical Education: Recommendations From Medical Students.

The medical community has been complicit in legitimizing claims of racial difference throughout the history of the United States. Unfortunately, a rigorous examination of the role medicine plays in perpetuating inequity across racial lines is often missing in medical school curricula due to time constraints and other challenges inherent to medical education. The imprecise use of race-a social construct-as a proxy for pathology in medical education is a vestige of institutionalized racism. Recent examples are presented that illustrate how attributing outcomes to race may contribute to bias and unequal care. This paper proposes the following recommendations for guiding efforts to mitigate the adverse effects associated with the use of race in medical education: emphasize the need for incoming students to be familiar with how race can influence health outcomes; provide opportunities to hold open conversations about race in medicine among medical school faculty, students, and staff; craft and implement protocols that address and correct the inappropriate use of race in medical school classes and course materials; and encourage a large cultural shift within the field of medicine. Adoption of an interdisciplinary approach that taps into many fields, including ethics, history, sociology, evolutionary genetics, and public health is a necessary step for cultivating more thoughtful physicians who will be better prepared to care for patients of all racial and ethnic backgrounds.

Perspectives of Caregivers on the Effects of Migration on the Nutrition, Health and Physical Activity of their Young Children: A Qualitative Study with Immigrant and Refugee Families.

To explore perspectives on nutrition, health and physical activity among immigrant parents with young children before and after migration. We conducted focus groups in five languages (Arabic, Somali, Dari, Burmese and Nepali), then conducted a phenomenological analysis of the transcripts. Fifty caregivers participated; 42% spent time in a refugee camp. Within the domain Change in Environment, four themes emerged: (1) food access; (2) family experiences with weight and growth; (3) differences in physical activity and perceptions of safety; and (4) health care experience. Within the domain of Parenting Behaviors and Experiences, two themes emerged: (1) Sociocultural differences in early feeding behaviors and (2) concern about feeding behaviors. To support health outcomes for refugee and immigrant families with young children, key focus areas for programming would include access to fresh foods, safe places for physical activity, and feeding practices following a family history of food scarcity.

Head Impact Exposure in Youth Soccer and Variation by Age and Sex.

OBJECTIVE: To examine variation in head impact exposure (HIE) by age and sex in youth soccer. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Youth soccer athletes (11-14 years old) in local clubs. EXPOSURES: Age and sex. OUTCOME MEASURES: Head impact exposure measured using adhesive-mounted accelerometers during 1 month of soccer. RESULTS: Forty-six youth athletes (54% female) participated. No athlete reported a concussion during the study. More males than females had at least 1 head impact ≥15 g (P = 0.02). Of those who sustained a head impact above the 15-g threshold (57%), females sustained HIE of greater magnitude than males (median 47.4 g vs 33.3 g, P = 0.04). Eighty-five percent of athletes on U14 teams had at least 1 head impact ≥15 g compared with 15% of athletes on U12 teams (P < 0.001). Poisson regression stratified by sex and controlling for team-suggested age effects were significant only for females (P = 0.02). There was significant variation in HIE by team. There were no decrements in concussion symptoms, health-related quality of life, or neuropsychological testing after 1 month of soccer play. CONCLUSIONS: There is significant variation in HIE in youth soccer, which seems to be influenced by age and sex. Further studies are needed to better understand potential significance for injury prevention.

Meningococcal serogroup B outbreak response University of Wisconsin-Madison.

A meningococcal serogroup B (MenB) outbreak at a large public university prompted an emergency response to immunize undergraduates. OBJECTIVE: To report on a successful meningococcal serogroup B (MenB) vaccine clinic response at a large public university. METHODS: We assembled the team leaders to write this case report. RESULTS: Activation of the emergency plan and points of dispensing required cooperation of many units on campus under the leadership of university health officials with support from Centers for Disease Control and Prevention, state division of public health and the city-county health department. Significant efforts to provide consistent messages to students and parents regarding the outbreak and the availability of the MenB vaccines were made. Volunteers were recruited to staff the clinics alongside university healthcare providers. Over 22,000 doses of vaccine were administered. CONCLUSION: We report our experience and lessons learned which may be helpful to universities in preventing and responding to disease outbreaks.

Clinical factors associated with decision to recommend methylphenidate treatment for children with ADHD in France.

European guidelines advise on best practices for the diagnosis and non-pharmacological and pharmacological treatment of attention-deficit hyperactivity disorder (ADHD). This study aimed to (1) assess whether clinician's decisions to initiate methylphenidate treatment in children diagnosed with ADHD are in accordance with European guidelines and (2) identify clinical factors associated with the decision to recommend methylphenidate prescription. 5 to 13-year-old patients with an ADHD diagnosis were consecutively evaluated in an outpatient child and adolescent psychiatry clinic in France. Patients underwent a multidisciplinary evaluation including a diagnostic interview, symptom severity assessments with parent questionnaires, and IQ testing. We compared children with (n = 105) and without (n = 55) recommended methylphenidate treatment using Student's t test or Wilcoxon Mann-Whitney test and Chi-square or Fisher's test. Multivariate logistic regression was implemented to determine the respective influence of each variable on treatment recommendation. Recommendation to initiate methylphenidate treatment was associated with (1) ADHD combined presentation, (2) co-occurring Oppositional Defiant Disorder/Conduct Disorder (ODD/CD), Developmental Coordination Disorder (DCD) and Learning Disorder (LD), (3) clinical severity and impairment indicated on parent questionnaires, and (4) reduced perceptual reasoning. Using a multivariate regression model, ADHD combined presentation [combined versus predominantly hyperactive/impulsive and unspecified OR 4.52 (1.23-16.55), p = 0.023], age [OR 1.46 (1.14-1.88), p = 0.003], ODD/CD [OR 5.53 (2.19-14.01), p < 0.001], DCD [OR 4.22 (1.70-10.48), p = 0.002], PRI [OR 0.97 (0.94-0.99), p = 0.01] were significantly associated with recommendation of methylphenidate treatment. Our results indicate that clinicians' treatment decision-making complies with European guidelines and is furthermore associated with the type and severity of ADHD symptoms but also with co-occurring disorders.

Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC-Driven Evolutionary Convergence.

Diverse pathways drive resistance to BRAF/MEK inhibitors in BRAF-mutant melanoma, suggesting that durable control of resistance will be a challenge. By combining statistical modeling of genomic data from matched pre-treatment and post-relapse patient tumors with functional interrogation of >20 in vitro and in vivo resistance models, we discovered that major pathways of resistance converge to activate the transcription factor, c-MYC (MYC). MYC expression and pathway gene signatures were suppressed following drug treatment, and then rebounded during progression. Critically, MYC activation was necessary and sufficient for resistance, and suppression of MYC activity using genetic approaches or BET bromodomain inhibition was sufficient to resensitize cells and delay BRAFi resistance. Finally, MYC-driven, BRAFi-resistant cells are hypersensitive to the inhibition of MYC synthetic lethal partners, including SRC family and c-KIT tyrosine kinases, as well as glucose, glutamine, and serine metabolic pathways. These insights enable the design of combination therapies that select against resistance evolution.

Longitudinal trajectories of post-concussive and depressive symptoms in adolescents with prolonged recovery from concussion.

PRIMARY OBJECTIVE: To investigate the symptom trajectories of depressive and post-concussive symptoms (PCS) in slow-to-recover adolescents to understand how the two sets of symptoms are related. RESEARCH DESIGN: We used data from a randomized clinical trial of a collaborative care intervention for post-concussive symptoms to better understand how these two sets of symptoms change in parallel over 6 months. METHODS AND PROCEDURE: PCS and depressive symptom scores for 49 adolescents (ages 11-17) were measured at enrolment and after 1, 3, and 6 months. Latent growth curve modelling for parallel processes was used to simultaneously examine change in PCS and depressive symptoms over time and to evaluate the influence of one change process on the other. MAIN OUTCOMES AND RESULTS: On average, patients enrolled 66 days following injury (Interquartile range (IQR) 43.5, 88.5). PCS and depressive symptoms were significantly associated at enrolment and over time, and both decreased over the course of 6 months. Higher PCS at enrolment predicted a greater decrease in depressive symptoms over time. CONCLUSIONS: Our results suggest that clinicians should screen for and treat depressive symptoms in patients with high post-concussive symptoms one month following injury.

The Epidemic of Despair Among White Americans: Trends in the Leading Causes of Premature Death, 1999-2015.

OBJECTIVES: To evaluate trends in premature death rates by cause of death, age, race, and urbanization level in the United States. METHODS: We calculated cause-specific death rates using the Compressed Mortality File, National Center for Health Statistics data for adults aged 25 to 64 years in 2 time periods: 1999 to 2001 and 2013 to 2015. We defined 48 subpopulations by 10-year age groups, race/ethnicity, and county urbanization level (large urban, suburban, small or medium metropolitan, and rural). RESULTS: The age-adjusted premature death rates for all adults declined by 8% between 1999 to 2001 and 2013 to 2015, with decreases in 39 of the 48 subpopulations. Most decreases in death rates were attributable to HIV, cardiovascular disease, and cancer. All 9 subpopulations with increased death rates were non-Hispanic Whites, largely outside large urban areas. Most increases in death rates were attributable to suicide, poisoning, and liver disease. CONCLUSIONS: The unfavorable recent trends in premature death rate among non-Hispanic Whites outside large urban areas were primarily caused by self-destructive health behaviors likely related to underlying social and economic factors in these communities.

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution.

Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs) with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

Babesiosis Surveillance - Wisconsin, 2001-2015.

Babesiosis is an emerging zoonotic disease caused primarily by Babesia microti, an intraerythocytic protozoan. Babesia microti, like the causal agents for Lyme disease and anaplasmosis, is endemic to the northeastern and upper midwestern United States where it is usually transmitted by the blacklegged tick, Ixodes scapularis. Although babesiosis is usually a mild to moderate illness, older or immunocompromised persons can develop a serious malaria-like illness that can be fatal without prompt treatment. The most common initial clinical signs and symptoms of babesiosis (fever, fatigue, chills, and diaphoresis) are nonspecific and present diagnostic challenges that can contribute to delays in diagnosis and effective treatment with atovaquone and azithromycin (1). Results of one study revealed a mean delay of 12-14 days from symptom onset to treatment (2). Knowledge of the incidence and geographic distribution of babesiosis can raise the index of clinical suspicion and facilitate more prompt diagnosis and lifesaving treatment (1). The first known case of babesiosis in Wisconsin was detected in 1985 (3), and babesiosis became officially reportable in the state in 2001. Wisconsin babesiosis surveillance data for 2001-2015 were analyzed in 3-year intervals to compare demographic, epidemiologic, and laboratory features among patients with cases of reported babesiosis. To determine possible reasons for an increase in reported Babesia infection, trends in electronic laboratory reporting and diagnosis by polymerase chain reaction testing (PCR) were examined. Between the first and last 3-year analysis intervals, there was a 26-fold increase in the incidence of confirmed babesiosis, in addition to geographic expansion. These trends might be generalizable to other states with endemic disease, similar suburbanization and forest fragmentation patterns, and warming average temperatures (4). Accurate surveillance in states where babesiosis is endemic is necessary to estimate the increasing burden of babesiosis and other tickborne diseases and to develop appropriate public health interventions for prevention and practice.

Viability of the World Health Organization quality of life measure to assess changes in quality of life following treatment for alcohol use disorder.

PURPOSE: Quality of life is an outcome often examined in treatment research contexts such as biomedical trials, but has been studied less often in alcohol use disorder (AUD) treatment. The importance of considering QoL in substance use treatment research has recently been voiced, and measures of QoL have been administered in large AUD treatment trials. Yet, the viability of popular QoL measures has never been evaluated in AUD treatment samples. Accordingly, the present manuscript describes a psychometric examination of and prospective changes in the World Health Organization Quality of Life measure (WHOQOL-BREF) in a large sample (N = 1383) of patients with AUD recruited for the COMBINE Study. METHODS: Specifically, we examined the construct validity (via confirmatory factor analyses), measurement invariance across time, internal consistency reliability, convergent validity, and effect sizes of post-treatment changes in the WHOQOL-BREF. RESULTS: Confirmatory factor analyses of the WHOQOL-BREF provided acceptable fit to the current data and this model was invariant across time. Internal consistency reliability was excellent (α > .9) for the full WHOQOL-BREF for each timepoint; the WHOQOL-BREF had good convergent validity, and medium effect size improvements were found in the full COMBINE sample across time. CONCLUSIONS: These findings suggest that the WHOQOL-BREF is an appropriate measure to use in samples with AUD, that the WHOQOL-BREF scores may be examined over time (e.g., from pre- to post-treatment), and the WHOQOL-BREF may be used to assess improvements in quality of life in AUD research.