Impact of ambient air pollution and socio-environmental factors on the health of children younger than 5 years in India: a population-based analysis.

Background: Ambient air pollution and household environmental factors affect child health, particularly in low-income and middle-income countries. This study aimed to investigate the association between ambient air pollution (PM2·5) levels, socio-environmental factors (including household wealth, housing quality measures, smoking status), and the occurrence of respiratory illness in Indian children. Methods: In this retrospective and observational study, we analysed data from India's National Family Health Survey (NFHS-5, 2019-2021) combined with NASA's Global Annual PM2·5 Grids database. Bivariate and multivariable generalized additive models were employed to examine associations between key social-environmental factors and respiratory illness in children younger than 5 years. Findings: We analysed data from 224,214 children younger than 5 years, representing 165,561 families from 29,757 geographic clusters. Our results showed extremely high annual PM2·5 levels throughout India (median 63·4·g/m3, IQR 41·9-81·6), with higher exposure for rural and impoverished families. In bivariate analyses, PM2·5 was significantly associated with reported respiratory illness (p < 0·001). Using generalized additive models and after accounting for key social and environmental factors, a monotonic increasing and non-linear relationship was observed between PM2·5 and respiratory illness (p < 0·001), with increased likelihood of illness observed even at values near and below India's National Ambient Air Quality Standards of 40 µg/m3. Interpretation: The study highlights the significant association of social-environmental conditions with health outcomes among young children in India. Efforts specifically targeting ambient air pollution and child health during monsoon season could have significant health benefits among this population and help achieve the goal of ending preventable deaths of children younger than 5 years. Funding: National Institutes of Health (NIH T-32-HL139443-3).

Missing the mark? Exploratory analysis of the 10-year-old cutoff as an independent marker of high-risk disease in pediatric B-ALL.

This single-center, retrospective study evaluated age as a risk factor for relapsed/refractory disease and/or death in 153 children with B-cell acute lymphoblastic leukemia. The study sample included children near the 10-year age cutoff for high-risk disease (6.0-13.9 years at diagnosis) and without other high-risk features (high white cell count, unfavorable cytogenetics). Children 10.0-13.9 years treated per high-risk protocols did not have inferior outcomes compared with children aged 6.0-9.9 years initiating treatment per standard-risk protocols. The study indicates that, in the era of cytogenetics, an age threshold of 10 years might not be an independent prognostic marker. Multicenter analyses are needed.

Bridging the Divide: Unintended Consequences of the Shift to Home-based Telemedicine.

OBJECTIVE: To evaluate the impact on healthcare access of the change in telemedicine delivery from a clinic-based model, in which patients connect with their healthcare provider from local telemedicine clinics, to a home-based model, in which patients independently connect from their homes. STUDY DESIGN: In this retrospective analysis, we compared relative uptake in telemedicine services in Period 1 (01/01/2019 - 03/15/2020, pre-pandemic, clinic-based model) versus Period 2 (03/16/2020 - 06/30/2022, home-based model) within a tertiary pediatric hospital system. Using multivariable logistic regression, we investigated the influence of telemedicine delivery model on patient sociodemographic characteristics of completed telemedicine visits. RESULTS: We analyzed 400,539 patients with 1,406,961 completed outpatient encounters (52% White, 35% Black), of which 62,920 (4.5%) were telemedicine. In the clinic-based model (Period 1), underserved populations had greater likelihoods of accessing telemedicine: Hispanic ethnicity (odds ratio (OR)=1.41, p=0.028) vs reference group non-Hispanic, Medicaid (OR=2.62, p<0.001) vs private insurance, and low-income neighborhood (OR=3.40, p<0.001) vs medium-income. In aggregate, telemedicine utilization rapidly increased from Period 1 (1.5 encounters/day) to Period 2 (107.9 encounters/day). However, underserved populations saw less relative increase (Medicaid [OR=0.28, p<0.001], Hispanic [OR=0.53, p<0.001], low-income [OR=0.23, p<0.001]). CONCLUSIONS: We observe that the clinic-based model offers more equitable access, while the home-based model offers more absolute access, suggesting that a hybrid model that offers both home-based and clinic-based services may result in more absolute and equitable access to telemedicine.

Nutritional Recovery of Children With HIV and Severe Acute Malnutrition Attending an Outpatient Therapeutic Care Program.

BACKGROUND: Despite significant morbidity and mortality from HIV and severe acute malnutrition (SAM) among children in sub-Saharan Africa, research is lacking in these children. We describe the proportion of children living with HIV with SAM achieving recovery, the factors associated with recovery, and time to recovery in an outpatient therapeutic care program. SETTING AND METHODS: This is a retrospective observational study of children with SAM and HIV on antiretroviral therapy (6 months-15 years), enrolled in outpatient therapeutic care from 2015 to 2017 at a pediatric HIV clinic in Kampala, Uganda. SAM diagnosis and recovery by 120 days after enrollment were determined per World Health Organization guidelines. Cox-proportional hazards models were used to determine predictors of recovery. RESULTS: Data from 166 patients were analyzed (mean age 5.4 years, SD 4.7). Outcomes showed 36.1% recovered, 15.6% were lost to follow-up, 2.4% died, and 45.8% failed. Average time to recovery was 59.9 days (SD 27.8). Patients 5 years or older were less likely to recover (crude hazard ratio [CHR] = 0.33, 95% CI: 0.18 to 0.58). In multivariate analysis, febrile patients were less likely to recover (adjusted hazard ratio = 0.53, 95% CI: 0.12 to 0.65). Patients with CD4 count of 200 or less at enrollment were less likely to recover (CHR = 0.46, 95% CI: 0.22 to 0.96). CONCLUSIONS: Despite treatment with antiretroviral therapy for children living with HIV, we observed poor rates of recovery from SAM, below the international target of >75%. Moreover, patients 5 years and older, fever, or low CD4 at diagnosis of SAM may require more intense therapy or closer monitoring than their counterparts.

Are children with sickle cell disease at particular risk from the harmful effects of air pollution? Evidence from a large, urban/peri-urban cohort.

INTRODUCTION: Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution's harmful effects. METHODS: Patient data were collected from a single-center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM2.5 ) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO2 ), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. RESULTS: From 2010 to 2018, there were 17,731 ED visits by 1740 children with SCD (64.8% HbSS/HbSß0 ). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Higher 3-day (lags 0-2) rolling mean PM2.5 and CO levels were associated with daily ED visits among those with SCD (PM2.5 incident rate ratio [IRR] 1.051 [95% confidence interval: 1.010-1.094] per 9.4 µg/m3 increase; CO 1.088 [1.045-1.132] per 0.5 ppm). NO2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. CONCLUSIONS: Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

Acute myeloid leukemia and dilated cardiomyopathy in a pediatric patient with D-2-hydroxyglutaric aciduria type I.

D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare neurometabolic disease with two main subtypes, caused by either inactivating variants in D2HGDH (type I) or germline gain of function variants in IDH2 (type II), that result in accumulation of the same toxic metabolite, D-2-hydroxyglutarate. The main clinical features of both are neurologic, including developmental delay, hypotonia, and seizures. Dilated cardiomyopathy is a unique feature thus far only reported in type II. As somatic variants in IDH2 are frequently identified in several different types of cancer, including acute myeloid leukemia (AML), a link between cancer and this metabolic disease has been proposed; however, there is no reported cancer in patients with either type of D-2-HGA. Murine models have demonstrated how D-2-hydroxyglutarate alters metabolism and epigenetics, a potential mechanism by which this metabolite may cause cancer and cardiomyopathy. Here, we report the first case of both AML and dilated cardiomyopathy in a pediatric patient with D-2-HGA type I, who was treated with an anthracycline-free regimen. This report may expand the clinical spectrum of this rare metabolic disease and provide insight on long-term surveillance and care. However, this case is complicated by the presence of a complex chromosomal rearrangement resulting in a 25.5 Mb duplication of 1q41 and a 2.38 Mb deletion of 2q37.3. Thus, the direct causal relationship between D-2-HGA and leukemogenesis or cardiomyopathy warrants further scrutiny.

"The flu is a little more complicated than a cold": Knowledge, beliefs, and practices related to influenza and influenza vaccination among at-risk populations and health professionals in Peru.

BACKGROUND: Influenza is a major source of morbidity and mortality with an annual global attack rate estimated at 5-10% in adults and 20-30% in children. Influenza vaccination is the main strategy for reducing influenza-related morbidity and mortality. Like several other countries, Peru has low vaccination coverage, estimated at 25-50% among young children and older adults. Therefore, the study objective was to explore the knowledge, beliefs, attitudes, and practices related to influenza vaccination among populations at higher risk for infection and/or complications and health professionals in Peru, and their perspectives on health communication channels. METHODS: This qualitative study was carried out in three cities. We held nine focus groups with pregnant and postpartum women, parents of young children, and older adults. We carried out 25 in-depth interviews with health professionals (HPs) working in, leading or advising immunization-related programs. RESULTS: HPs correctly identified the causes of influenza and HPs and at risk community members identified major symptoms. Community members had poor awareness of the potential severity of influenza and were generally unaware of influenza-related mortality. Both HPs and community members greatly underestimated the prevalence of influenza in Peru. HPs in our study overestimated major side effects of the influenza vaccine and community members perceived that the vaccine caused illness. HPs missed important opportunities to promote vaccination in patients with minor illness (runny nose, allergies, colds) and community members did not understand that the vaccine should be received annually. CONCLUSIONS: There is no single strategy that will increase influenza vaccination rates to World Health Organization recommended levels. Instead, it requires multi-faceted commitment from HPs, other healthcare authorities and the government. Addressing important knowledge barriers, specifically negative views regarding the influenza vaccine and the severe morbidity and mortality associated with influenza illness, both in the community and especially among HPs, could have significant impacts.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

OBJECTIVES: HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. METHODS: The study was a retrospective cohort study (study period 2004-2018). Cases of HIV + and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV + controls without SCD (HIV+/SCD-). RESULTS: Thirty-five HIV+/SCD + subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6 years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD + had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P = 0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD + and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD + cohort (P = 0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD + cohort showed a more rapid rise and higher total CD4 count (P = 0.012, regression analysis). CONCLUSION: The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD + achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

OBJECTIFS: Le VIH et la drépanocytose (SCD) sont des causes importantes de morbidité et de mortalité en Afrique subsaharienne. Compte tenu de leurs rôles distincts dans la dérégulation immunitaire, notre objectif était de caractériser l'impact du SCD sur la présentation et la progression du VIH pédiatrique. MÉTHODES: Etude de cohorte rétrospective (période d'étude 2004-2018). Les cas de patients VIH+ atteints de SCD (VIH+/SCD+) ont été obtenus par analyse des dossiers électroniques dans une clinique pédiatrique du VIH à Kampala, en Ouganda et appariés dans une proportion 1:3 avec des témoins VIH+ sans SCD (VIH+/SCD-). RÉSULTATS: 35 sujets VIH+/SCD+ et 95 témoins VIH+/SCD- ont été analysés (39% de femmes (51/130), 3,6 ans d'âge (SD3,9)). Au départ, le stade clinique de l'OMS (64% de la cohorte totale au stade III/IV) et l'état nutritionnel (9,4% de malnutrition aiguë sévère) étaient similaires pour les deux groupes, tandis que les VIH+/SCD+ avaient un nombre de CD4 de base plus élevé mais non significatif (1036 (DS, 713) vs 849 (DS, 638) cellules/microlitre, p = 0,20, test t bilatéral). Il y a eu 19 décès, 6 (17%) VIH+/SCD+ et 13 (14%) VIH+/SCD-, avec des modèles non ajustés/ajustés ne montrant aucune différence significative. La progression nutritionnelle et la progression du stade clinique n'ont montré aucune différence significative entre les groupes. L'analyse de Kaplan-Meier a montré un taux d'échecs de traitement plus lent dans la cohorte VIH+/SCD+ (p = 0,11, test de survie log-rank). L'analyse de la trajectoire a montré que dans la période analysée, la cohorte VIH+/SCD+ a montré une augmentation plus rapide et un nombre total de CD4 plus élevé (p = 0,012, analyse de régression). CONCLUSION: L'étude suggère que SCD n'affecte pas négativement la progression du VIH chez les patients sous ART. De plus, les patients VIH+/SCD+ ont atteint un nombre plus élevé de CD4 et moins d'échecs de traitement du VIH, ce qui suggère que les effets physiologiques dus à la SCD pourraient atténuer la progression du VIH.

Cryptococcal meningitis and immune reconstitution inflammatory syndrome in a pediatric patient with HIV after switching to second line antiretroviral therapy: a case report.

BACKGROUND: Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published. CASE PRESENTATION: A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter. Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free. CONCLUSIONS: We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.

Analysis of management decisions and outcomes of a weekly multidisciplinary pediatric tumor board meeting in Uganda.

AIM: To evaluate the efficacy of a pediatric multidisciplinary tumor board (MTB) in Uganda. PATIENTS & METHODS: We documented the discussion of cases presented at a pediatric MTB and subsequently, though retrospective chart review, determined the degree to which decision were implemented. RESULTS: 95 patients were discussed. In total, 129 of 226 (57%) distinct management decisions reached during the MTBs were implemented. Of these, 15 resulted in changes in diagnosis and 53 were classified as major changes in management. Decisions on chemotherapy were the most likely to be successfully enacted (51/58), followed by radiotherapy (18/30) and surgery (12/21). Labs/consults were less likely to be implemented. CONCLUSION: Key improvements, specifically in the documentation and implementation of management decisions, are needed to improve the MTB's efficacy.

Sexual Risk, Behavior, and HIV Testing and Status among Male and Transgender Women Sex Workers and their Clients in Lima, Peru.

OBJECTIVES ­: To determine the socio-demographics, sexual practices, and HIV prevalence of male sex workers (MSWs), transwomen sex workers (TSWs), and their male clients in Lima, Peru. METHODS ­: Following ethnographic mapping of sex work venues, we revisited randomly selected venues to survey MSWs, TSWs and their clients. RESULTS ­: MSWs and TSW clients are more educated than MSW clients and TSWs. Only 50% of TSW clients have received HIV testing. Self-reported HIV positivity is highest among MSW clients and TSWs. CONCLUSION ­: Notable differences exist between MSWs and TSWs and their clients that can affect the health of these groups and warrant intervention.

The Earning and Spending Habits of Male Sex Workers in Lima, Peru.

Over the past decade, data have identified male sex work as a potentially viable economic decision; despite this, male sex workers (MSWs) continue to be perceived as group with access to few assets and resources. Using data from a pilot skills- building intervention for MSWs in Lima, Peru, an analysis of the economic characteristics of 209 MSWs is presented. The majority reported livable incomes with median earnings of US$250 per month, 83% earning above the urban poverty line. Interestingly, non-sex work was also an important source of income, especially for the high-earning MSWs. Spending data revealed that a large portion of income went to necessities (55%), luxuries (11%), and gifts (11%), with less toward savings (5%) and studies (1%). Such data on MSWs' earnings and spending, which suggest that a lack of overall income is not the MSW's main impediment to escaping poverty, could direct future poverty alleviation and health improvement programs in this key population.

A Retrospective Analysis of Sociodemographic and Hematologic Characteristics Associated With Achieving Optimal Hydroxyurea Therapy in Children With Sickle Cell Disease.

Hydroxyurea (HU) has proven hematologic and clinical benefits, especially when escalated to the maximum tolerated dose (MTD). We reviewed clinical data from patients with sickle cell disease (January 2011 to 2016) to determine baseline sociodemographic and laboratory parameters associated with reaching HU MTD without significant delays. In total, 210 patients (mean HU start age, 6.6 y) were included. Initial Kaplan-Meier event analysis showed 1 year to be an inflection point for reaching MTD. In total, 116 patients (55%) reached MTD in <1 year, with 56 (27%) taking >1 year to reach MTD and 38 (18%) patients not successfully reaching MTD during follow-up. In both crude and adjusted analyses, age at HU start was found to be significantly and inversely associated with reaching MTD within 1 year. The data presented, specifically the inflection point of reaching MTD at 1 year and the association of young HU start age with reaching MTD within a year, suggest that successful achievement of MTD may be facilitated by starting patients on HU at a young age and that older patients should receive additional intervention to attain MTD within 1 year. Patients who do not achieve MTD within a year may need the most extensive intervention.

An Analysis of and Recommendations for the Peruvian Blood Collection and Transfusion System.

BACKGROUND: Peru experienced a crisis in its blood collection and supply system in the mid-2000s, as contaminated blood led to several transfusion-transmitted infections (TTI), occurring in the backdrop of extremely low voluntary donation rates and a national blood supply shortage. Thus, the Peruvian Ministry of Health (MINSA) implemented a national investigation on the safety and quality of the Peruvian blood collection/transfusion network. METHODS: Every Peruvian blood bank was evaluated by MINSA from 2007-2008. These evaluations consisted of an update of the national registry of blood banks and visits to each blood bank from MINSA oversight teams. Information was collected on the condition of the blood bank personnel, equipment, supplies, and practices. Further, previously-collected blood at each blood bank was randomly selected and screened for TTI-causing pathogens. RESULTS: Uncovered in this investigation was a fragmented, under-equipped, and poorly-staffed blood collection and transfusion network, consisting of 241 independent blood banks and resulting in suboptimal allocation of resources. Further, blood with evidence of TTI-causing pathogens (including Hepatitis B, Hepatitis C, and syphilis) and set for transfusion was discovered at three separate blood banks as part of the random screening process. CONCLUSION: Using the successful reorganizations of national blood supply systems in other Latin American countries as examples, Peru would be well-served to form large, high-volume, regional blood collection and transfusion centers, responsible for blood collection and screening for the entire country. The small, separate blood banks would then be transformed into a network of blood transfusion centers, not responsible for blood collection. This reorganization would allow Peru to better utilize its resources, standardize the blood collection and transfusion process, and increase voluntary donation, resulting in a safer, more abundant national blood product.

Is Intimate Partner and Client Violence Associated with Condomless Anal Intercourse and HIV Among Male Sex Workers in Lima, Peru?

Violence experience can increase HIV risk behaviors; however, literature is scarce on violence among male sex workers (MSWs) globally. In 2014, 210 Peruvian MSWs (median age 24.9) were interviewed about their experience of physical, emotional, and sexual violence and condom use with non-paying intimate partners and clients and were tested for HIV. Multivariable models examined relationships between violence in the past 6 months, condomless anal intercourse (CLAI) in the past 3 months and HIV infection. HIV infection (24 %), CLAI (43 %), being a violence victim (42 %) and perpetrator (39 %) were common. In separate multivariable models, being a violence victim [adjusted prevalence ratio aPR = 1.49 (95 % CI 1.09-2.03)] and perpetrator [aPR = 1.39 (1.03-1.87)] were associated with CLAI. Further, being a victim [aPR = 1.65 (1.04-2.62)] was associated with HIV infection. Violence, which was significantly associated with CLAI and HIV infection, is common among Peruvian MSWs, reinforcing the importance of violence awareness and prevention as HIV risk-reduction strategies.