Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

BACKGROUND: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. METHODS: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. RESULTS: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). CONCLUSIONS: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.

Explaining utilization of HIV prevention and testing services among university students in Mozambique: results from a mixed methods study.

BACKGROUND: In Mozambique, HIV infection disproportionately affects young adults, particularly women. Despite awareness and knowledge of HIV transmission, many university students have not received HIV testing and continue to engage in high-risk sexual behaviors, including inconsistent condom use. Further understanding of patterns of engagement with HIV prevention and testing is key to reducing HIV transmission in this at-risk population. METHODS: This study used a sequential mixed methods approach to examine patterns of engagement and perceptions of HIV prevention and testing services among higher education students in Mozambique. Survey data were collected from a representative sample of 501 students from Universidade Eduardo Mondlane (UEM) in Maputo, Mozambique to assess the primary outcomes of 1) HIV testing within the last 12 months; and 2) condom use during last sexual encounter. We employed univariate and multivariate regression models. The survey was followed by qualitative interviews with 70 survey participants which were analyzed using an inductive, content-focused analysis to further explain and contextualize survey findings. RESULTS: Over 85% of students reported to be sexually active, among these 74% reported condom use during their last sexual encounter, and 64.2% reported an HIV test within the past 12 months. Females were more likely to have had HIV testing in the past 12 months in comparison to their male peers (aOR 1.82, 95% CI 1.11, 2.99), but were half as likely to have used a condom with their last sexual encounter (aOR 0.52, 95% CI 0.33, 0.83), when controlling for other factors. Qualitative data suggests that these discrepancies may be explained by differential perceptions in risk and trust/mistrust, with women being more concerned about infidelity by their male partner(s) and assuming more responsibility for knowing their own serostatus. Women were also subject to negative stereotypes for possessing condoms in comparison to men, which could explain lower propensity for use. CONCLUSION: Given gendered differences in uptake of condom use and HIV testing, and perceived HIV risk, interventions tailored specifically to male and female students may impact engagement with HIV prevention and testing and empower informed choices about sexual behaviors.

High Frequency of Antibiotic Prescription in Children With Undifferentiated Febrile Illness in Kenya.

BACKGROUND: In low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood. METHODS: This study examined clinical presentation and management of a cohort of febrile Kenyan children at 5 hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics. RESULTS: Of 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (ie, cough, runny nose), HEENT findings on exam (ie, nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status). CONCLUSION: In a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult, given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills.

Factors Motivating Traditional Healer versus Biomedical Facility Use for Treatment of Pediatric Febrile Illness: Results from a Qualitative Study in Southwestern Uganda.

Febrile illnesses, such as malaria and pneumonia, are among the most common causes of mortality in children younger than 5 years in Uganda outside of the neonatal period. Their impact could be mitigated through earlier diagnosis and treatment at biomedical facilities; however, it is estimated that a large percentage of Ugandans (70-80%) seek traditional healers for their first line of medical care. This study sought to characterize individual and structural influences on health care-seeking behaviors for febrile children. Minimally structured, qualitative interviews were conducted for 34 caregivers of children presenting to biomedical and traditional healer sites, respectively. We identified six themes that shape the pathway of care for febrile children: 1) peer recommendations, 2) trust in biomedicine, 3) trust in traditional medicine, 4) mistrust in providers and therapies, 5) economic resources and access to health care, and 6) perceptions of child health. Biomedical providers are preferred by those who value laboratory testing and formal medical training, whereas traditional healer preference is heavily influenced by convenience, peer recommendations, and firm beliefs in traditional causes of illness. However, most caregivers concurrently use both biomedical and traditional therapies for their child during the same illness cycle. The biomedical system is often considered as a backup when traditional healing "fails." Initiatives seeking to encourage earlier presentation to biomedical facilities must consider the individual and structural forces that motivate seeking traditional healers. Educational programs and cooperation with traditional healers may increase biomedical referrals and decrease time to appropriate care and treatment for vulnerable/susceptible children.

Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya.

BACKGROUND: Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya. METHODS: A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes. RESULTS: The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children. CONCLUSION: Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels.

Parental perception of efficacy of antihistamines for pruritus in pediatric atopic dermatitis.

BACKGROUND: Clinicians have previously prescribed antihistamines for relief of atopic dermatitis (AD) associated pruritus. The use of antihistamines in AD has recently received less emphasis from newly published practice parameters that currently only recommend short-term, intermittent use of first-generation antihistamines to induce sleep in patients with AD. OBJECTIVE: Our study aimed to determine parents' perception of the usefulness of antihistamines in reducing their child's itch due to AD. METHODS: A 12-question survey was mailed to parents of patients who were attending a pediatric allergy clinic. Patients with physician-diagnosed AD who had a clinic visit in the past 3 years were included. Questions included the following: time since AD diagnosis, itching frequency, impact on sleep, frequency and relief provided from using antihistamines, and comparison of antihistamines to other antipruritus treatments. RESULTS: Sixty-three percent of parents surveyed responded that antihistamines were helpful in the management of their child's AD, and only 5% did not find any itch relief. The majority of the responders were parents of younger patients (ages, 2-10 years) with immunoglobulin E sensitization and AD for more than a year. Eighty-five parents (68.5%) reported no interruption of sleep due to itching, and, among them, an almost equal number were currently solely using either a first- or second-generation antihistamine. The more antihistamines were perceived as relieving itching, the more they were used (ρ = 0.209, p = 0.025) and provided more relief than other products (ρ = -0.336, p < 0.001). When compared, parents ranked antihistamines to be as helpful as topical corticosteroids. CONCLUSION: Parents of pediatric patients with AD found that antihistamines were an important part of AD management.

The Accuracy of ICD Codes: Identifying Physical Abuse in 4 Children's Hospitals.

OBJECTIVE: To assess the accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes in identifying cases of child physical abuse in 4 children's hospitals. METHODS: We included all children evaluated by a child abuse pediatrician (CAP) for suspicion of abuse at 4 children's hospitals from January 1, 2007, to December 31, 2010. Subjects included both patients judged to have injuries from abuse and those judged to have injuries from accidents or to have medical problems. The ICD-9-CM codes entered in the hospital discharge database for each child were compared to the decisions made by the CAPs on the likelihood of abuse. Sensitivity and specificity were calculated. Medical records for discordant cases were abstracted and reviewed to assess factors contributing to coding discrepancies. RESULTS: Of 936 cases of suspected physical abuse, 65.8% occurred in children <1 year of age. CAPs rated 32.7% as abuse, 18.2% as unknown cause, and 49.1% as accident/medical cause. Sensitivity and specificity of ICD-9-CM codes for abuse were 73.5% (95% confidence interval 68.2, 78.4), and 92.4% (95% confidence interval 90.0, 94.0), respectively. Among hospitals, sensitivity ranged from 53.8% to 83.8% and specificity from 85.4% to 100%. Analysis of discordant cases revealed variations in coding practices and physicians' notations among hospitals that contributed to differences in sensitivity and specificity of ICD-9-CM codes in child physical abuse. CONCLUSIONS: Overall, the sensitivity and specificity of ICD-9-CM codes in identifying cases of child physical abuse were relatively low, suggesting both an under- and overcounting of abuse cases.

Identification of physical abuse cases in hospitalized children: accuracy of International Classification of Diseases codes.

OBJECTIVE: Hospital discharge databases are being increasingly used to track the incidence of child physical abuse in the United States. These databases use International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to categorize illnesses and injuries in hospitalized patients. We assessed the accuracy of the assignment of these codes for cases of child physical abuse. STUDY DESIGN: Participants were all children (N = 133) evaluated by a child abuse pediatrician (CAP) for suspicion of abuse at Yale-New Haven Children's Hospital from January 1, 2007-December 31, 2010. These children included both those judged to have injuries from abuse and those judged to have injuries accidental/medical in nature. We compared the ICD-9-CM codes entered in the hospital discharge database for each child with the decisions made by the CAPs, as documented in their child abuse registry. The CAPs' decisions were considered to be the gold standard. Sensitivity and specificity were calculated. Medical records were reviewed for cases in which the ICD-9-CM codes disagreed with the CAP's decision. RESULTS: In 133 cases of suspected child physical abuse, the sensitivity and specificity of ICD-9-CM codes for abuse were 76.7 % (CI 61.4%, 88.2%) and 100% (CI 96.0%, 100%), respectively. Analysis of the 10 cases of abuse not receiving ICD-9-CM codes for abuse revealed that errors in physician documentation (n = 5) and in coding (n = 5) contributed to the reduction in sensitivity. CONCLUSIONS: Despite high specificity in identifying child physical abuse, the sensitivity of ICD-9-CM codes is 77%, indicating that these codes underestimate the occurrence of abuse.

An accelerated state of myosin-based actin motility.

We use an in vitro motility assay to determine the biochemical basis for a hypermotile state of myosin-based actin sliding. It is widely assumed that the sole biochemical determinant of actin-sliding velocities, V, is actin-myosin detachment kinetics (1/tauon), yet we recently reported that, above a critical ATP concentration of approximately 100 microM, V exceeds the detachment limit by more than 2-fold. To determine the biochemical basis for this hypermotile state, we measure the effects of ATP and inorganic phosphate, Pi, on V and observe that at low [ATP] V decreases as ln [Pi], whereas above 100 microM ATP the hypermotile V is independent of Pi. The ln [Pi] dependence of V at low [ATP] is consistent with a macroscopic model of muscle shortening, similar to Hill's contractile component, which predicts that V varies linearly with an internal force (Hill's active state) that drives actin movement against the viscous drag of myosin heads strongly bound to actin (Hill's dashpot). At high [ATP], we suggest that the hypermotile V is caused by shear thinning of the resistive population of strongly bound myosin heads. Our data and analysis indicate that, in addition to contributions from tauon and myosin's step size, d, V is influenced by the biochemistry of myosin's working step as well as resistive properties of actin and myosin.