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Tuberculosis (TB) preventive therapy (TPT) is increasingly recognized as the key to eliminating tuberculosis globally and is particularly critical for children with TB infection or who are in close contact with individuals with infectious TB. But many barriers currently impede successful scale-up to provide TPT to those at high risk of TB disease. The cascade of care in TB infection (and the related contact management cascade) is a conceptual framework to evaluate and improve the care of persons who are potential candidates for TPT. This review summarizes recent literature on barriers and solutions in the TB infection care cascade, focusing on children in both high- and low-burden settings, and drawing from studies on children and adults. Identifying and closing gaps in the care cascade will require the implementation of tools that are new (e.g. computer-assisted radiography) and old (e.g. efficient contact tracing), and will be aided by innovative implementation study designs, quality improvement methods, and shared clinical practice with primary care providers.

US guidelines recommend interferon gamma release assays (IGRAs) for diagnosis of tuberculosis infection in children. In this retrospective cohort study, IGRA use in children 2-17 years of age increased substantially between 2015 and 2021. Testing in inpatient/subspecialty settings (vs. primary care), public (vs. private) insurance, lower age and non-English preferred language were associated with increased odds of receiving an IGRA.

To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery.We conducted a retrospective cohort study of children (age18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included.We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71).Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion.

Objective To develop a conceptual theory to describe how financial strain affects women with young children to inform clinical care and research. Design Qualitative, grounded theory. Setting Participants were recruited from the waiting area of a pediatric clinic and an office of the Special Supplemental Nutrition Program for Women, Infants, and Children embedded within the largest safety-net academic medical center in New England. Participants were interviewed privately at the medical center or in the community. Participants Twenty-six English-speaking women, mostly single and African American/Black, with at least one child 5 years old or younger, were sampled until thematic saturation was met. Methods We used grounded theory methodology to conduct in-depth, semistructured interviews with participants who indicated that they experienced financial strain. We analyzed the interview data using constant comparative analysis, revised the interview guide based on emerging themes, and developed a theoretical model. Results Five interrelated themes emerged and were developed into a theoretical model: Financial Strain Has Specific Characteristics and Common Triggers, Financial Strain Is Exacerbated by Inadequate Assistance and Results in Tradeoffs, Financial Strain Forces Parenting Modifications, Women Experience Self-Blame, and Women Experience Mental Health Effects. Conclusion For women with young children, financial strain results in forced tradeoffs, compromised parenting practices, and self-blame, which contribute to significant mental health problems. These findings can inform woman-centered clinical practice and advocacy interventions. Women’s health care providers should identify families experiencing financial strain, provide referrals to financial services, and join advocacy efforts to advance social policies that address the structural causes of poverty, such as increased minimum wage and paid family leave.

This case demonstrates the importance of considering septic pulmonary embolism (SPE) on the differential for chest pain in the pediatric population, especially in patients with a history of skin and soft tissue infection. The adolescent patient in this report, with a history of axillary hidradenitis suppurativa complicated by methicillin-resistant Staphylococcus aureus (MRSA) superinfection and recent completion of a 3-month course of doxycycline, presented with isolated focal chest pain in the absence of other infectious or respiratory signs or symptoms. Initial pulmonary imaging revealed multiple bilateral wedge-shaped nodules. Three specialty teams were consulted in the patient's evaluation, resulting in biopsy of a suspicious lesion that confirmed the diagnosis of MRSA SPE. Following a course of targeted antibiotic therapy, the patient's chest pain resolved and imaging findings improved. Insights gleaned from the workup of this patient are useful in formulating a framework for recognition of SPE in children presenting with chest pain, and also highlight the importance of considering insidious SPE presentation in the setting of antibiotic pretreatment.

Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.

To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19).We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization.A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization.SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization.

Background Distribution of long-lasting insecticide treated nets (LLINs) is the most widely used intervention for the prevention of malaria but recall and social desirability biases may lead to challenges in accurately measuring use of bednets. SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time. Assessing local acceptability is important when implementing innovative global health technologies such as SmartNet. This study draws on established models such as the Technology Acceptance Model (TAM) and Theoretical Framework of Acceptability (TFA) to assess acceptability of SmartNet in Ugandan households. Methods Semi-structured qualitative interviews were conducted at weeks one and six following installation of SmartNet in ten households in Western Uganda. Heads-of-households answered open-ended questions addressing the main acceptability domains of the TFA and TAM models (i.e. perceived ease of use, ethicality, etc.). Responses were digitally recorded, transcribed, coded and analyzed using a thematic analysis approach. Results Seven out of ten households interviewed reported no difference in use between SmartNet and a standard LLIN. Households stated the large size, soft fabric, and the efficacy of SmartNet relative to a standard LLIN contributed to perceived usefulness and perceived ease of use. Opportunity costs of the novel monitoring system expressed by households included difficulty washing nets and dislike of blinking lights on the device. Barriers to SmartNet use focused on questions of the ethics of bednet use monitoring, discomfort with technical aspects of the device and a poor understanding of its function amongst others in the community. However, explaining SmartNet to other community members resolved these concerns and often resulted in interest and acceptance among peers. Conclusion Objective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to behaviors around use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education. The device will continue to be optimized to make it more acceptable to users and to accurately reflect standard LLIN use to improve our understanding of prevention behaviors in malaria endemic settings.

Objective Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre. Study design We identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C. Results We identified 50 confirmed MIS-C cases (MIS-C+) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C-). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C+ patients. MIS-C+ and MIS-C- patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension. Conclusions Among hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features., This single centre cohort study identifies clinical and laboratory findings that distinguish multisystem inflammatory syndrome in children (MIS-C) from other febrile illnesses in which MIS-C was considered but ultimately excluded. The most discriminative features of MIS-C included older age, conjunctivitis, oral mucosa changes, abdominal pain and hypotension, higher neutrophil/lymphocyte ratios and lower platelet counts.

OBJECTIVES: Atrial fibrillation (AF) is a major risk factor for stroke, which is the leading cause of cardiovascular mortality in sub-Saharan Africa. However, there is limited population-based epidemiological data on AF in sub-Saharan Africa. We sought to estimate the prevalence and correlates of AF in rural Uganda. METHODS: We conducted a cross-sectional study using community health fairs in 2015 targeting eight villages in rural Uganda. Study participants completed a medical history, a clinical exam, blood collection, and 12-lead electrocardiographic (ECG) screening. Of 1,814 participants enrolled in a parent cohort study that includes 98% of adults residing in the geographic area, 856 attended a health fair and were included in this study. Our primary outcome was AF or atrial flutter. We modelled population prevalence of the outcome with inverse probability of treatment weighting using data collected from the full population. RESULTS: 856 (47.2%) adults in the area attended a health fair and were included in the analysis. Health fair attendees were older (42 vs 34 years, p

OBJECTIVES: To characterize the socioeconomic and racial and/or ethnic disparities impacting the diagnosis and outcomes of multisystem inflammatory syndrome in children (MIS-C). METHODS: This multicenter retrospective case-control study was conducted at 3 academic centers from January 1 to September 1, 2020. Children with MIS-C were compared with 5 control groups: children with coronavirus disease 2019, children evaluated for MIS-C who did not meet case patient criteria, children hospitalized with febrile illness, children with Kawasaki disease, and children in Massachusetts based on US census data. Neighborhood socioeconomic status (SES) and social vulnerability index (SVI) were measured via a census-based scoring system. Multivariable logistic regression was used to examine associations between SES, SVI, race and ethnicity, and MIS-C diagnosis and clinical severity as outcomes. RESULTS: Among 43 patients with MIS-C, 19 (44%) were Hispanic, 11 (26%) were Black, and 12 (28%) were white; 22 (51%) were in the lowest quartile SES, and 23 (53%) were in the highest quartile SVI. SES and SVI were similar between patients with MIS-C and coronavirus disease 2019. In multivariable analysis, lowest SES quartile (odds ratio 2.2 [95% confidence interval 1.1–4.4]), highest SVI quartile (odds ratio 2.8 [95% confidence interval 1.5–5.1]), and racial and/or ethnic minority background were associated with MIS-C diagnosis. Neither SES, SVI, race, nor ethnicity were associated with disease severity. CONCLUSIONS: Lower SES or higher SVI, Hispanic ethnicity, and Black race independently increased risk for MIS-C. Additional studies are required to target interventions to improve health equity for children.

HIV status disclosure remains one of the major challenges to effective HIV prevention. Given the complexities and low rates of disclosure, new innovative strategies are needed. Since electronic adherence monitoring (EAM) are unique mobile devices that light up when transmitting data, those who see them often want to know more about them, which can potentially result in HIV status disclosure. We conducted a qualitative study to explore patient experiences with EAM for antiretroviral therapy (ART) in Uganda with a goal of understanding potential ethical concerns, including disclosure. Unexpectedly, several participants reported intentionally using EAM to facilitate HIV status disclosure to others in order to get social support, encourage HIV testing, and create awareness about HIV. Although researchers and clinicians need to be mindful of the potential for unintended HIV status disclosure through the use of EAM, they should also recognize the potential of this approach to support intended disclosure.

Clinical features of Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 are nonspecific. In this retrospective cohort study of 39 patients evaluated for MIS-C, 11 had non-SARS-CoV-2 infections, 3 of whom were also diagnosed with MIS-C. Clinical features were similar in patients with MIS-C and patients with non-SARS-CoV-2 infections. Clinicians should consider non-SARS-CoV-2 infections in patients undergoing MIS-C evaluation.

* Abbreviations: COVID-19 — : coronavirus disease 2019 CQ — : chloroquine HCQ — : hydroxychloroquine SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Should children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection receive antiviral therapy? If so, what should we give, to which children, and for what disease severity? Despite brisk scientific progress elucidating the biology and transmission of SARS-CoV-2, and numerous adult trials testing antiviral therapies, we may pass the formative stages of this pandemic without defining antiviral agents’ appropriate role in pediatric management. We urgently need pediatric clinical trials to establish the efficacy, safety, and pharmacokinetics of the most promising experimental and repurposed coronavirus disease 2019 (COVID-19) therapies proposed to date.1 Researchers of early reports show that pediatric SARS-CoV-2 infection tends to be mild but that some children develop severe disease.2 In these reports, researchers highlight differences between pediatric and adult COVID-19 and argue that risk/benefit calculations of therapies derived from adult trials cannot be readily extrapolated to children. Gaps in our knowledge of pediatric COVID-19 further complicate assessments of risk and benefit. To date, we have a limited understanding of viral kinetics or immune responses in children, what factors predispose some children to severe disease, or how these variables affect responses to therapies. We have equally limited comprehension of how SARS-CoV-2 affects children with primary immunodeficiencies, illnesses requiring immune-compromising therapies, or other complex conditions. Nonetheless, treatment planning for severe pediatric cases, even if they will be few, has spurred children’s hospitals to develop algorithms that include antiviral agents, such as remdesivir, chloroquine (CQ), and … Address correspondence to Jeffrey I. Campbell, MD, Division of Infectious Diseases, Boston Children’s Hospital, 333 Longwood Ave, 6th Floor, Boston, MA 02115. E-mail: jeffrey.campbell{at}childrens.harvard.edu

Children who travel internationally to visit friends and relatives (VFRs) are at risk for travel-related illness, but underuse pretravel health services. Although primary care clinics can identify travelers and address pretravel health needs, to date, there are few published reports on effective primary care–based pretravel interventions. We developed a quality improvement initiative to increase traveler identification at a primary care clinic serving families that frequently travel to VFRs. Interventions included a screening question asked at all clinic visits, provider and staff training, travel fliers, and health recommendation sheets for families. Interventions were implemented during 2017 and 2018 peak travel seasons. Travel visit rates and characteristics during the intervention period were compared with pre-intervention baseline periods (April–August, 2015–16). Surveys with providers were conducted to assess disruptiveness of the interventions, and rates of duplicate travel visits were assessed. A total of 738 unique travel events were identified during peak travel seasons from 2015 to 2018, encompassing travel to 29 countries across five continents. Overall, there were 428 unique travel events (3.0% of all clinic visits) during peak seasons 2017–18, compared with 310 unique travel events (2.2% of all clinic visits) during peak seasons 2015–16 (rate ratio 1.34 [95% CI: 1.16–1.56], P < 0.001). None of the 18 healthcare providers or staff surveyed found new travel screening processes to be disruptive or bothersome. Implementation of a primary care–based multimodal travel screening and education initiative was associated with a significantly increased rate of travel visits.

Objectives The World Health Organization recommends empowering patients/families to remind healthcare workers (HCWs) to perform hand hygiene (HH). We sought to understand acceptability of a family empowerment strategy in a Vietnamese pediatric intensive care unit (PICU). Methods With end-user input, we designed a tool to help families in a PICU in Vietnam to remind HCWs to perform HH. We conducted 3 preliminary focus group discussions (FGDs) with patients’ family members (n = 8), physicians (n = 9), and nurses (n = 8) to understand acceptability of preliminary tools, attitudes towards HH and barriers to HH. Tools were then modified and implemented in a 5-week intervention study. We then conducted 3 more FGDs with families (n = 7), physicians (n = 7), and nurses (n = 8). Discussions were analyzed using qualitative directed content analysis. Families who used the tool were asked to complete written surveys. Findings Both family members and HCWs felt that HCWs had a responsibility to perform HH. Barriers to performing HH were identified, including forgetfulness and time constraints. Family members felt shy reminding HCWs to perform HH. However, the HH reminder tool was acceptable, and some felt it could overcome barriers to reminding HCWs to perform HH. HCWs felt embarrassed when reminded to perform HH, but felt that the reminder was useful. Nearly all (99%) survey respondents felt that family members should speak up if they noticed HCWs omitting HH. Conclusions A tool given to families to remind HCWs to perform HH was largely acceptable in a pediatric ICU in Vietnam. Perceived benefits of improving HH were felt to surmount barriers to tool use.

Background: Guidelines recommend empowering patients and families to remind healthcare workers (HCWs) to perform hand hygiene (HH). The effectiveness of empowerment tools for patients and their families in Southeast Asia is unknown. Methods: We performed a prospective study in a pediatric intensive care unit (PICU) of a Vietnamese pediatric referral hospital. With family and HCW input, we developed a visual tool for families to prompt HCW HH. We used direct observation to collect baseline HH data. We then enrolled families to receive the visual tool and education on its use while continuing prospective collection of HH data. Multivariable logistic regression was used to identify independent predictors of HH in baseline and implementation periods. Results: In total, 2,014 baseline and 2,498 implementation-period HH opportunities were observed. During the implementation period, 73 families were enrolled. Overall, HCW HH was 46% preimplementation, which increased to 73% in the implementation period (P < .001). The lowest HH adherence in both periods occurred after HCW contact with patient surroundings: 16% at baseline increased to 24% after implementation. In multivariable analyses, the odds of HCW HH during the implementation period were significantly higher than baseline (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 2.54–3.41; P < .001) after adjusting for observation room, HCW type, time of observation (weekday business hours vs evening or weekend), and HH moment. Conclusions: The introduction of a visual empowerment tool was associated with significant improvement in HH adherence among HCWs in a Vietnamese PICU. Future research should explore acceptability and barriers to use of similar tools in low- and middle-income settings.

With technology permeating nearly every aspect of daily life, it is no surprise that digital medicine is taking on an increasingly important role in medical care. In their sweeping analysis of ethi...

Novel monitoring technologies in HIV research, such as electronic adherence monitors (EAMs), have changed the nature of researcher-participant interactions. Yet little is known about how EAMs and the resulting interaction between researchers and participants affect research participation and the data gathered. We interviewed participants and research assistants (RAs) in an observational cohort study involving EAMs for HIV antiretroviral therapy (ART) in Uganda. We qualitatively explored interviewees' views about ethical issues surrounding EAMs and assessed data with conventional and directed content analysis. Participants valued their relationships with RAs and were preoccupied with RAs' perceptions of them. Participants were pleased when the EAM revealed regular adherence, and annoyed when it revealed non-adherence that contradicted self-reported pill-taking behavior. For many, the desire to maintain a good impression incentivized adherence. But some sought to creatively conceal non-adherence, or refused to use the EAM to avoid revealing non-adherence to RAs. These findings show that participants' perceptions of the study staff's perceptions of them affected the experience of being monitored, study participation, and ultimately the data gathered in the study. Investigators in monitoring-based research should be aware that social interactions between participants and study staff could affect both the practical and ethical conduct of that research.

Providing ancillary care is sometimes obligatory in medical and health care studies. Its provision may, however, collide with achievement of a study’s aims. How should researchers respond when that happens?

Many new technologies monitor patients' and study participants' medical adherence. Some have cautioned that these devices transgress personal autonomy and ethics. But do they? This qualitative study explored how Ugandan study participants perceive the effect of electronic monitoring of their adherence to antiretroviral therapy (ART) on their freedoms to be non-adherent and pursue other activities that monitoring may inadvertently expose. Between August 2014 and June 2015, we interviewed 60 Ugandans living with HIV and enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) study, a longitudinal, observational study involving electronic adherence monitors (EAMs) to assess ART adherence. We also interviewed 6 UARTO research assistants. Both direct and indirect content analysis were used to interpret interview transcripts. We found that monitoring created a sense of pressure to adhere to ART, which some participants described as "forcing" them to adhere. However, even participants who felt that monitoring forced them to take medications perceived using the EAM as conducive to their fundamental goal of high ART adherence. Overall, even if monitoring may have limited participants' effective freedom to be non-adherent, participants welcomed any such effect. No participant rejected the EAM on the grounds that it would limit that effective freedom. Reports that monitoring altered behaviors unrelated to pill-taking were rare. Researchers should continue to be vigilant about the ways in which behavioral health monitoring affects autonomy, but should also recognize that even autonomy-limiting monitoring strategies may enable participants to achieve their own goals.

Highlights In this study of middle-aged adults in rural Uganda, we found no difference in the prevalence of abnormal or ischemic electrocardiograms between persons with human immunodeficiency virus (HIV) on stable antiretroviral therapy and HIV-negative comparators. Women were more than twice as likely than men to have evidence of myocardial ischemia on electrocardiography, independent of HIV serostatus. This difference persisted after adjustment. Additional research is warranted to better evaluate sex-based differences in cardiovascular risk and to further characterize the contributions of HIV cardiovascular disease in this population.

Visiting friends and relatives (VFRs) tend to have a higher prevalence of travel-related infectious diseases than other tourists. In addition, health care workers face special concerns when working abroad. Many illnesses, mostly infectious in origin, are associated with travel but can often be prevented. It is crucial to inquire about the countries traveled to, time of travel, travel activities, and basic health status to determine what illnesses need to be considered in a returning traveler who is sick. There are many websites that provide accurate, current information about travel-related health risks.

Background Hand hygiene (HH) is the most effective way to prevent healthcare-associated infections. The World Health Organization (WHO) recommends empowering patients and families to remind healthcare workers (HCWs) to perform HH. The effectiveness of patient and family empowerment tools in Southeast Asia is unknown. Methods We performed a prospective intervention study in an intensive care unit of a pediatric referral hospital in Vietnam. Using family and HCW input, we created a visual tool for families to use to remind HCWs to perform HH. For 2 weeks pre-intervention, we collected baseline data on HH performance, method (hand rub or soap and water), adequacy, HCW type (e.g., physician, nurse), and WHO 5 moments of HH using direct, unobtrusive observation. During a subsequent 3-week intervention period, consenting families were provided the visual tool and educated on its use to prompt HCW HH. Prospective collection of outcome data continued during the intervention period. The primary outcome was change in HCW HH between baseline and intervention periods. Multivariable logistic regression models were used to identify independent predictors of HH. Results A total of 2,014 pre-intervention and 2,498 intervention period HH opportunities were observed. During the intervention period, 73 families received visual reminder tools and education. Overall HCW HH was 46% pre-intervention, which increased to 73% in the intervention period (P < 0.001). Lowest HH adherence in both periods occurred after HCW contact with patient surroundings (WHO Moment 5; 16% pre-intervention and 24% intervention). In multivariable analyses, the odds of HCW HH during the intervention period were significantly higher than pre-intervention (OR 2.94 [95% CI 2.54 – 3.41], P < 0.001) after adjusting for observation room, HCW type, time of observation (weekday business hours vs. evening/weekend), and HH moment. Among completed HH opportunities, HH adequacy was >90% in both periods. Conclusion Introduction of a visual empowerment tool was associated with significant improvement in HH adherence among HCWs in a Vietnamese pediatric intensive care unit. More research is needed to explore acceptability and barriers to the use of such tools in other low- and middle-income settings. Disclosures All authors: No reported disclosures.

Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards “Big Brother” in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised.

Purpose: Several pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging���residual cancer burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)���have been developed to characterize residual tumors when patients do not achieve pCR. The optimal system and the ways in which these systems complement each other have not been fully determined. Methods: Using data from the I-SPY 1 TRIAL, we compared pCR, RCB, and yAJCC as predictors of early recurrence-free survival (RFS) to identify ways to improve post-neoadjuvant pathologic evaluation. Results: Among 162 patients assessed, pCR identified patients at lowest risk of recurrence, while RCB and yAJCC identified patients at highest risk. Hormone-receptor (HR) and HER2 subtypes further improved risk prediction. Recursive partitioning indicated that triple-negative or HER2+ patients with yAJCC III or RCB 3 have the highest recurrence risk, with an RFS of 27%. Our analysis also highlighted discrepancies between RCB and yAJCC stratification: 31% of patients had discrepant RCB and yAJCC scores. We identified differential treatment of lymph node involvement and tumor cellularity as drivers of these discrepancies. Conclusions: These data indicate that there is benefit to reporting both RCB and yAJCC for patients in order to identify those at highest risk of relapse.

Insecticide-treated bednets (ITNs) are a mainstay of malaria prevention, yet poor adherence poses a major barrier to effective prevention. Self-reports of bednet use suffer from recall and social desirability biases. We have designed a device that electronically records ITN usage longitudinally. SmartNet consists of circuits made from a conductive fabric interwoven into the sides and top of a rectangular ITN. Digital sampling of the state of these circuits allows for determining whether the SmartNet is deployed for use or folded up. We conducted a study among pregnant women and women with children

Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve.

To the editor—We appreciate the thoughtful comments raised by Wolbers and Day [1] in response to our article [2]. We agree with their primary point—that our meta-analysis summarized data across studies, and it is therefore best suited to evaluate study-level and not individual-level predictors of outcomes. We should have specified more clearly that our analysis is best suited for drawing inferences about relationships among patient populations, but not about individual patients. Indeed, this point is true for almost all meta-analysis, and it also applies to most individual randomized trials [3]. It is important to note that we did not intend to imply that combination amphotericin B and flucytosine conferred a benefit in patients with cryptococcal meningitis with altered mental status. Rather, in our meta-analysis, we were unable to identify a statistically significant treatment benefit across all published literature, for combination amphotericin B with flucytosine over amphotericin B alone. Although there was some implication of a benefit from adjunctive flucytosine in a subanalysis limited to studies that included patients with altered levels of consciousness, this estimate was not statistically significant (odds ratio = 0.56; 95% confidence interval [CI], .23–1.43) (Figure ​(Figure1).1). As such, we hypothesized in the discussion that populations with altered consciousness might be more likely to benefit from adjunctive flucytosine therapy. If this hypothesis were correct, it would require patient-level data for confirmation. Figure 1. Forrest plot from network meta-analysis comparing odds of early (2-week) and late (10-week) mortality between combination amphotericin B and flucytosine with amphotericin B alone for human immunodeficiency virus-associated cryptococcal meningitis. Abbreviations: ... In their recent large, randomized trial, Day et al [4] demonstrated superiority of combination amphotericin B and flucytosine over amphotericin B alone at 10 weeks. They now present a subanalysis with patient-level data that suggests that those with a normal Glasgow Coma Score (GCS) appeared to derive as much benefit (if not more) from the addition of flucytosine as those with a GCS < 15. Although their study was not powered to detect differences in these subgroups, their data do lend support to the use of flucytosine in individual patients with normal mental status within their study population. It should be noted that the overall mortality in their study was 36% at 10 weeks (and 30% among those who received amphotericin B and flucytosine combination therapy). In contrast, the only other large randomized trial to compare amphotericin B alone with amphotericin B and adjunctive flucytosine found no difference in mortality between groups at 10 weeks (6.7% versus 6.9%; relative risk = 0.97; 95% CI, .46–2.04) [5]. It is noteworthy that this other study was conducted in the United States, excluded comatose patients from enrollment, and had a lower prevalence of participants with altered mental status than the Day et al [4] study (11% vs 28%). We believe that the contrasting data from these 2 studies are in line with our overall conclusion: that current available evidence suggests that the adjunctive use of flucytosine might be beneficial in populations with advanced disease who are at high overall risk for mortality. As Wolbers and Day [4] point out, this does not necessarily mean that patients with normal mental status will not benefit from adjunctive flucytosine, only that populations with low overall risk of mortality are less likely to benefit. Unfortunately, for the time being, it appears that flucytosine is largely only available and in use in the areas of the world where the current data suggest it has the least benefit, whereas populations with the highest mortality often cannot access it [6, 7]. Indeed, the most important conclusion we draw from our study is that more data is required, across a range of patient populations and disease stages, to elucidate which drugs are needed for which patients, and to ensure that the optimal therapies are available to those who need them.

Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not ide.jpegy a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis.

Malaria is a serious health concern for three billion people worldwide, killing nearly 600,000 people a year. Insecticide-treated bednets (ITNs) are an effective and valuable tool for preventing malaria and hundreds of millions of ITNs have been distributed throughout sub-Saharan Africa. Nevertheless, our current methods for measuring ITN use are inadequate to inform malaria prevention programs. The most common method, self-reported ITN use, is limited by 1) social desirability, 2) recall and 3) sampling bias. An acceptable objective and longitudinal method of assessing adherence to ITN use would improve our ability to better understand the determinants of ITN use and design more effective malaria prevention interventions. We describe the development and initial proof-of-concept validity testing of an ITN adherence monitoring tool called SmartNet. SmartNet uses conductive thread interwoven into an ITN and a microcontroller to detect the state of the ITN. We tested SmartNet among five volunteers using the device over their beds in Boston, USA for two weeks with the goal of evaluating device reliability, accuracy and acceptability to inform future device improvements. The device recorded data for 63.1% (35172/55711) of installed two-minute time intervals, with 97.3% (19990/20539) of the recording errors relating to battery failures. Overall, the device was 71.7% (25204/35172) accurate in determining the state of the ITN (whether it was folded up or unfurled) and performed significantly better at detecting an unfurled ITN than a folded ITN, 77.3% versus 68.4% (p

Background. Colorectal cancer screenings are underused in HIV-infected patients, but reasons for underuse have not been examined. Methods. Using a standardized questionnaire, HIV-infected patients aged !50 years were asked if they had a colorectal cancer screening and what factors influenced their decisions. Results. Among 55 patients (53 [96%] male; mean age 57 years [range: 51-71]); 35 (64%) ever received colorectal cancer screenings, 2 (4%) were scheduled for screening, 16 (29%) had never been screened, and 2 (4%) provided unusable results. Patients screened were more likely to remember discussing colorectal cancer (P < .01) and colorectal cancer screenings (P < .01) with a medical practitioner. Conclusions. In this population of HIV-infected patients >50 year olds, a significant minority of patients did not undergo the colorectal cancer screening. Discussions about the colorectal cancer screenings and colorectal cancer risk appear to have a significant impact on a patient's decision to be screened.

Background Intensive glycaemic control in type one diabetes (T1D) reduces progression of complications (DCCT and EDIC). In clinical practice, glycosylated haemoglobin (Hba1c) levels reflect control. Previous studies show that higher 25(OH)D3 levels are associated with lower Hba1c (US SEARCH study). However, there are limited interventional trials assessing the effect of cholecalciferol on Hba1c. Aims. 1. To assess the baseline 25(OH)D3 status in a paediatric cohort of patients with T1D. 2. To determine the effect of cholecalciferol administration on Hba1c. Methods Children with T1D attending routine clinic appointments from February to April 2011 had blood samples taken with consent, and patients with a 25(OH)D3 level 10 years) units. Hba1c levels from the year preceding treatment and the year after treatment were recorded. Results Vitamin D levels were obtained from 51 patients (30 male, 21 female). 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 subjects were vitamin D deficient, but 2 were excluded from the analysis (one moved away, one was non-compliant). All South Asian patients were vitamin D deficient, with mean 25(OH)D3 of 11.2 ng/ml. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1C (r= –0.484, p Conclusion We confirmed a high prevalence of vitamin D deficiency in this clinic cohort of children with T1D, and found a negative relationship between baseline 25(OH)D3 level and HbA1C in Caucasians. However, in patients treated with a stat dose of cholecalciferol there was no effect on Hba1c. Further studies with larger sample sizes, and using maintenance 25(OH)D3 therapy rather than stat therapy are required.

Background: Numerous studies have demonstrated that, in addition to inherent qualities of antiretroviral (ARV) medications, adherence is affected by demographic, socioeconomic, and psychological factors. There are limited data about factors affecting adherence to antiretroviral therapy (ART) among HIV-infected persons in urban Guatemalan HIV care centers. Methods: Participants were patients at an urban, free-care public clinic in Guatemala City and obtained medications from a closed-pharmacy system. Nonpregnant patients ≥18 years who received medications from the Global Fund to Fight AIDS, Tuberculosis & Malaria, who had taken ARV medications for ≥12 weeks, who arrived for an appointment at the clinic, and who provided informed consent were interviewed. Adherence was measured using pharmacy pill counts and patient self-reports. Recent biological markers for each patient were collected from the clinic’s database, and χ 2 and descriptive statistics were used to analyze results. Results: Among 122 patients interviewed, mean adherence by pill count was 97%. A total of 110 patients (90%) had adherence ≥95% using pharmacy pill counts, and 108 (89%) had adherence ≥95% using self-reports. Virologic failure (viral load [VL] ≥500 copies/mL) was significantly less common among patients with ≥95% adherence (P = .02). Family and spousal support for treatment were significantly associated with ≥95% adherence (P = .01 and .003, respectively). The presence of stavudine (d4T) in a patient’s regimen was significantly associated with