Preventing Diabetic Foot Re-Ulceration Through an Innovative Pressure and Temperature Monitoring Clinical Device.

This study compared the outcome of an innovative in-shoe pressure and temperature measuring device as an adjunct to standard clinical care for diabetic foot versus standard clinical care alone. It included 88 participants with Type 2 diabetes mellitus with a history of one or more plantar foot ulceration who were already using prescription orthoses. These were randomly divided into the control group (n = 44, standard care only) and the experimental group (n = 44, standard care plus the innovative device). Both groups were monitored for re-ulceration for one year. Overall, the control group exhibited a higher number of re-ulcerations (n = 14) with 2 amputations in comparison with the experimental group (only 2 ulcerations and no amputations) at the end of the study. In conclusion, this innovative in-shoe pressure and temperature measuring device appears to reduce re-ulcerations by offering objective data for clinical decision making in the management of the diabetic high-risk foot.

Residential and healthcare mobility during pregnancy among women living with HIV in the UK, 2009-2019.

INTRODUCTION: The extent to which individuals living with HIV experience residential and healthcare mobility during pregnancy in the UK is unknown. We aimed to determine a minimum estimate of residential and healthcare mobility during pregnancy in people living with HIV in the UK in 2009-2019 to explore patterns of and factors associated with mobility and to assess whether mobility was associated with specific HIV outcomes. METHODS: We analyzed data from the Integrated Screening Outcomes Surveillance Service to assess pregnancies with HIV in the UK and included livebirths and stillbirths with estimated delivery in 2009-2019. Residential mobility was defined as changing residential postcode between notification and delivery, and healthcare mobility was defined as changing NHS Trust or Strategic Health Authority (SHA) in that same timeframe. We used logistic regression to determine factors associated with residential and healthcare mobility and with detectable delivery viral load. RESULTS: Among 10 305 pregnancies, 19.6% experienced residential mobility, 8.1% changed NHS Trust, and 4.5% changed SHA during pregnancy. Mobility was more likely to be experienced by younger women, migrants, and those with new antenatal diagnosis; residential but not healthcare mobility declined over time. In a fully adjusted model, mobility was not associated with having a detectable viral load at delivery. Higher proportions of infants were lost to follow-up after mobile pregnancies than after non-mobile pregnancies. CONCLUSIONS: This analysis provides new knowledge on mobility during pregnancy in the context of HIV, but further research is needed to understand its broader impacts and its utility as a marker to help identify families requiring additional follow-up and support.

Effectiveness and Safety of Direct-acting Antivirals for Treatment of Adolescents With HCV/HIV Coinfection: Real-world Data From Europe.

We evaluated the effectiveness and safety of direct-acting antivirals in adolescents with hepatitis C (HCV)/HIV coinfection using pooled individual patient-level data from 5 European cohorts. Of 122 participants in follow-up from November 2013 to August 2021, 19 were treated <18 years of age; of 15 with HCV RNA available at/after 12 weeks post-treatment, all had sustained virologic response with acceptable safety. This evidence addresses an important gap in knowledge of treatment outcomes in adolescents with HCV/HIV coinfection in real-life settings.

Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: an international Delphi consensus study "PC-COS Children".

The coronavirus disease 2019 (COVID-19) pandemic substantially impacted different age groups, with children and young people not exempted. Many have experienced enduring health consequences. Presently, there is no consensus on the health outcomes to assess in children and young people with post-COVID-19 condition. Furthermore, it is unclear which measurement instruments are appropriate for use in research and clinical management of children and young people with post-COVID-19. To address these unmet needs, we conducted a consensus study, aiming to develop a core outcome set (COS) and an associated core outcome measurement set (COMS) for evaluating post-COVID-19 condition in children and young people. Our methodology comprised of two phases. In phase 1 (to create a COS), we performed an extensive literature review and categorisation of outcomes, and prioritised those outcomes in a two-round online modified Delphi process followed by a consensus meeting. In phase 2 (to create the COMS), we performed another modified Delphi consensus process to evaluate measurement instruments for previously defined core outcomes from phase 1, followed by an online consensus workshop to finalise recommendations regarding the most appropriate instruments for each core outcome. In phase 1, 214 participants from 37 countries participated, with 154 (72%) contributing to both Delphi rounds. The subsequent online consensus meeting resulted in a final COS which encompassed seven critical outcomes: fatigue; post-exertion symptoms; work/occupational and study changes; as well as functional changes, symptoms, and conditions relating to cardiovascular, neuro-cognitive, gastrointestinal and physical outcomes. In phase 2, 11 international experts were involved in a modified Delphi process, selecting measurement instruments for a subsequent online consensus workshop where 30 voting participants discussed and independently scored the selected instruments. As a result of this consensus process, four instruments met a priori consensus criteria for inclusion: PedsQL multidimensional fatigue scale for "fatigue"; PedsQL gastrointestinal symptom scales for "gastrointestinal"; PedsQL cognitive functioning scale for "neurocognitive" and EQ-5D for "physical functioning". Despite proposing outcome measurement instruments for the remaining three core outcomes ("cardiovascular", "post-exertional malaise", "work/occupational and study changes"), a consensus was not achieved. Our international, consensus-based initiative presents a robust framework for evaluating post-COVID-19 condition in children and young people in research and clinical practice via a rigorously defined COS and associated COMS. It will aid in the uniform measurement and reporting of relevant health outcomes worldwide.

Resurgence of congenital syphilis: new strategies against an old foe.

Congenital syphilis is a major global cause of fetal loss, stillbirth, neonatal death, and congenital infection. In 2020, the global rate of congenital syphilis was 425 cases per 100 000 livebirths-substantially higher than WHO's elimination target of 50 cases per 100 000 livebirths. Case rates are rising in many high-income countries, but remain low compared with those in low-income and middle-income settings. This Review aims to summarise the current epidemiology and knowledge on transmission and treatment of syphilis in pregnancy, and proposes measures to reduce the rising incidence seen worldwide. We also describe emerging diagnostic and treatment tools to prevent vertical transmission and improve management of congenital syphilis. Finally, we outline a programme of public health priorities, which include research, clinical, and preventive strategies.

Setting the research agenda: involving parents in research on children who are HIV-free.

INTRODUCTION: There is growing interest in health, developmental and survival outcomes of children who are born HIV-free to women living with HIV (children born HIV-free). To date, the research agenda has been largely determined by researchers, funders and policy makers, with limited involvement of parents, who are key stakeholders. Researchers at UCL Great Ormond Street Institute of Child Health in partnership with community-based organisation 4M Network of Mentor Mothers conducted two workshops with parents in March 2022 to establish research priorities for children born HIV-free, and key considerations for methodological approaches both to research and engagement with the affected communities. DISCUSSION: When exploring research on children born HIV-free, we consider the following: what aspects of current research are aligned with women and parents' priorities, what is missing and what approaches would be preferred. A holistic approach to research on children born HIV-free should be prioritised, focussing on a breadth of outcomes and how they intersect. Secondary use of existing data sources should be maximised to facilitate this, with a view of monitoring the long-term effects of fetal antiretroviral drug exposure alongside other key health and developmental outcomes. Involving and engaging with parents, and children where possible, must be at the heart of research design to maximise relevance and impact of findings for the affected communities. Potential barriers to engaging with individuals who were children born HIV-free include parental disclosure and individuals not identifying as a child born HIV-free to a mother living with HIV. Stigma-free language must be incorporated into the vocabulary of researchers and other stakeholders, avoiding reference to exposure; we propose the term "children born HIV-free." CONCLUSIONS: Mothers and parents living with HIV should be involved in research about their children born HIV-free and are key in identifying research priorities so that findings may translate into an impact on their children's health and wellbeing. Meaningful involvement of women living with HIV through trusted community partners is an effective mechanism by which to elicit views on research about their children.

Digital Foot Technology in Ulcer Prevention and Reulceration: A Clinical Perspective.

BACKGROUND: Studies have shown that personal and economic reasons determine whether clinicians use diagnostic technology in their routine clinical biomechanical practice. This study aimed to identify the biomechanical management plan of local clinicians in relation to management of the diabetic high-risk foot and to investigate whether diagnostic technology is being used to determine the effectiveness of dispensed prescription orthoses in view of ulcer prevention. METHODS: A mixed-methodologic approach was adopted in this study. A retrospective quantitative study was also conducted to access records of patients attending the biomechanics clinic at a local health biomechanics clinic. Outcomes of interest included the number and percentage of patients attending the biomechanics clinic, source of referral to this clinic, age and gender of patients, clinical diagnosis, management plan, and referral pathway. Following a phenomenologic approach, four experienced clinicians working in the private, primary, and tertiary health sectors were interviewed. Thematic analysis was used to analyze and interpret data. RESULTS: Only low-risk patients living with diabetes mellitus were referred for a comprehensive biomechanical examination; the majority were referred by podiatrists. There was no record of diabetic high-risk patients being referred for a detailed biomechanical assessment within the health service. This study also confirmed that, because of the expenses and laborious work involved when using diagnostic technology to assess foot pressures, interviewed clinicians based their treatment plan and tested the efficiency of dispensed offloading devices on the basis of clinical experience and visual observation only. CONCLUSIONS: Waiting for signs of ulceration can be too late for the high-risk foot. A change in clinical practice is recommended where the integration of diagnostic technology, together with standard care, in view of ulcer prevention is warranted.

Innovative single-sensor, in-shoe pressure and temperature monitoring device: A static laboratory validation study.

BACKGROUND: To perform laboratory static validation of pressures from an innovative, single-sensor pressure and temperature monitoring device for the early detection of complications in the high-risk foot. RESEARCH QUESTION: Can an innovative, newly developed, in-shoe pressure and temperature measuring device, detect and measure the in-shoe peak plantar pressures and skin temperature as accurately as the reference standard? METHODS: A pressure generating rig, the Tekscan™ Equilibration 'bladder calibrator', was used to produce a known force, against the gold standard, FScan™ in-shoe pressure mapping system by Tekscan™ and a newly developed prototype. The F-scan® system was used to record the pressure readings and establish a baseline for the readings recorded utilising the prototype. A total of 20 pressure values were recorded with 100 samples each. RESULTS: Exploratory data analysis was conducted to gain insights and analyse the prototype's behaviour at different pressure points. Pre-processing and data cleaning were also performed to remove any anomalies. Support Vector Regressor with a polynomial kernel and Grid-Search algorithm was used to fit the recorded data curve. The best combination of parameters had a Mean Squared Error of 2.59 and a Root Mean Squared Error of 1.61. A simple linear equation was used to convert raw readings to pressure values. SIGNIFICANCE: The results of this study conclude that the pressure measurements taken with the prototype are congruent to the gold standard, F-scan® in-shoe system. This confirms that the prototype is a valid device that can be used safely as a low-cost alternative to current costly commercial in-shoe pressure mapping devices.

Gestational diabetes in women living with HIV in the UK and Ireland: insights from population-based surveillance data.

INTRODUCTION: The prevalence of gestational diabetes (GD) is increasing globally. While universal risk factors for GD are reasonably well understood, questions remain regarding risks for women living with HIV (WLWH). We aimed to describe GD prevalence, evaluate associated maternal risk factors and assess specific birth outcomes in WLWH in the UK and Ireland. METHODS: We analysed all pregnancies (≥24 weeks' gestation) in women diagnosed with HIV before delivery, reported to the UK-based Integrated Screening Outcomes Surveillance Service between 2010 and 2020. Every report of GD was considered as a case. A multivariable logistic regression model, adjusted for women with more than one pregnancy fitted with generalized estimating equations (GEE) assessed the effect of independent risk factors. RESULTS: There were 10,553 pregnancies in 7916 women, of which 460 (4.72%) pregnancies had reported GD. Overall, the median maternal age was 33 years (Q1:29-Q3:37), and 73% of pregnancies were in Black African women. WLWH with GD (WLWH-GD) were older (61% vs. 41% aged ≥35 years, p < 0.001) and more likely to be on treatment at conception (74% vs. 64%, p < 0.001) than women without GD. WLWH-GD were more likely to have a stillbirth (odds ratio [OR]: 5.38, 95% CI: 2.14-13.5), preterm delivery (OR: 2.54, 95% CI: 1.95-3.32) and fetal macrosomia (OR: 1.14, 95% CI: 1.04-1.24). Independent risk factors for GD included estimated year of delivery (GEE-adjusted odds ratio [GEE-aOR]: 1.14, 95% CI: 1.10-1.18), advanced maternal age (≥35 years) (GEE-aOR: 2.87, 95% CI: 1.54-5.34), Asian (GEE-aOR: 2.63, 95% CI: 1.40-4.63) and Black African (GEE-aOR: 1.55, 95% CI: 1.13-2.12) ethnicity. Timing and type of antiretroviral therapy showed no evidence of a relationship with GD in multivariable analyses; however, women with a CD4 count ≤350 cells/µl were 27% less likely to have GD than women with CD4 counts >350 cells/µl (GEE-aOR: 0.73, 95% CI: 0.50-0.96). CONCLUSIONS: GD prevalence increased over time among WLWH but was not significantly different from the general population. Maternal age, ethnicity and CD4 count were risk factors based on available data. Stillbirth and preterm delivery were more common in WLWH-GD than other WLWH over the study period. Further studies are required to build upon these results.

Effectiveness of Iontophoresis in Treating Plantar Hyperhidrosis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of tap water iontophoresis as a treatment for plantar hyperhidrosis. METHODS: Thirty participants living with idiopathic plantar hyperhidrosis and consented to undergo treatment using iontophoresis were recruited. The Hyperhidrosis Disease Severity Score was used to evaluate the severity of the condition before and after treatment. RESULTS: Tap water iontophoresis was found to be effective in the treatment of plantar hyperhidrosis in the study group (P = .005). CONCLUSIONS: Treatment with iontophoresis led to the reduction of disease severity and improvement of quality of life, and it is a safe, easy-to-use method with minimal side effects. This technique should be considered before the use of systemic or aggressive surgical interventions, which could have potentially more severe side effects.

Characteristics, treatment and care of pregnant women living with hepatitis B in England: findings from a national audit.

Around 0.4% of pregnant women in England have chronic hepatitis B virus (HBV) infection and need services to prevent vertical transmission. In this national audit, sociodemographic, clinical and laboratory information was requested from all maternity units in England for hepatitis B surface antigen-positive women initiating antenatal care in 2014. We describe these women's characteristics and indicators of access to/uptake of healthcare. Of 2542 pregnancies in 2538 women, median maternal age was 31 [IQR 27, 35] years, 94% (1986/2109) were non-UK born (25% (228/923) having arrived into the UK <2 years previously) and 32% (794/2473) had ⩾2 previous live births. In 39%, English levels were basic/less than basic. Antenatal care was initiated at median 11.3 [IQR 9.6, 14] gestation weeks, and 'late' (⩾20 weeks) in 10% (251/2491). In 70% (1783/2533) of pregnancies, HBV had been previously diagnosed and 11.8% (288/2450) had ⩾1 marker of higher infectivity. Missed specialist appointments were reported in 18% (426/2339). Late antenatal care and/or missed specialist appointments were more common in pregnancies among women lacking basic English, arriving in the UK ⩽2 years previously, newly HBV diagnosed, aged <25 years and/or with ⩾2 previous live births. We show overlapping groups of pregnant women with chronic HBV vulnerable to delayed or incomplete care.

Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi.

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs.

Innovative single-sensor, in-shoe pressure and temperature monitoring device: A dynamic laboratory validation study.

BACKGROUND: Available technology to detect the 2 primary predictors of ulceration is not being used as it is deemed as costly and time-consuming. Thus, the aim of this study was to determine dynamic laboratory validation, of an innovative, single-sensor in-shoe device that can read peak pressure and temperature simultaneously. RESEARCH QUESTION: Can an innovative, newly developed, in-shoe pressure and temperature measuring device, detect and measure the in-shoe peak plantar pressures and skin temperature of healthy participants, as accurately as the reference standard? METHODS: Five healthy adult participants were recruited. The prototype was validated against the gold standard FScan™ in-shoe system for pressures and the Flir® T630sc thermographic camera for temperatures. Participants were asked to walk at a comfortable pace on an electric treadmill for 13 min. The prototype and the FScan in-shoe sensors™ were superimposed inside the shoe of the participant, with the prototype on top, to ensure direct contact with the area of interest. Two thermographic images were captured using the Flir® T630sc thermographic camera, before and after the walk. During the trials, the participants wore 100 % cotton socks and their own sports shoes and pressures were recorded at 50 readings a second. RESULTS: The raw readings of pressure were passed to the regressor, which returned the estimated kPa value. Several evaluations metrics were used to evaluate the performance of the modal. The prototype gave equal results to that of the gold standard, the FScan™ in-shoe system. With regards to temperature measurements, both devices gave similar readings. SIGNIFICANCE: This innovative single-sensor, in-shoe pressure and temperature monitoring device showed similar measurements of pressure to the FScan™ system and temperature measurements were equivalent to the Flir® T630sc thermographic camera. The authors are confident that the innovative, low cost, single-sensor, in-shoe pressure and temperature monitoring device can be used as an alternative to the costly available commercial devices that measure pressure and temperature separately to detect early signs of complications in the high-risk foot.

Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment.

BACKGROUND: Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. METHODS: Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA-negative infants in whom RNA was not detectable until after 6 weeks. RESULTS: Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1-18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0-76.9), 39.7% (CrI, 17.9-65.9), and 20.9% (CrI, 4.6-44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. CONCLUSIONS: Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment.

Perinatal characteristics and longer-term outcomes in Brazilian children with confirmed or suspected congenital Zika infection: ZIKAction Paediatric Registry.

Background: Despite growing scientific knowledge of Zika virus (ZIKV) infection, questions remain regarding ZIKV infection in pregnancy and congenital ZIKV syndrome (CZS). Methods: The ZIKAction Paediatric Registry is an international registry of children with documented ZIKV exposure in utero and/or with confirmed or suspected CZS. Its aim is to characterize these children (i.e., clinical, radiological, neurodevelopmental features) and describe outcomes, longer-term sequelae and management through retrospective case note review. This analysis described the maternal and perinatal characteristics of children in the Registry's Bahia arm, assessed their neuroimaging, ophthalmic, hearing and electroencephalography abnormalities by microcephaly classification and reported on hospitalisations. Children born in 2015-2018 and enrolled 2020-2021 in three public health facilities in Salvador were included. Results: Of 129 (57% female) children, 15 (11·6%) had laboratory-confirmed congenital ZIKV infection and 114 (88·4%) suspected CZS. At delivery, 15 (11·6%) were normocephalic, 30 (23·3%) moderately microcephalic, and 84 (65·1%) severely microcephalic. Median birth head circumference z-score was -3·51 [IQR, -4·69,-2·73]. During follow-up, all children had abnormal neuroimaging, 80·3% (94/117) abnormal electroencephalogram, 62·2% (77/120) ophthalmic abnormalities, and 27·4% (34/124) hearing impairment. Microcephaly classification was significantly associated with gestational age, and ophthalmological and electroencephalography abnormalities. Of 125 children with hospitalisation data, 52 (41·6%) had been hospitalised by most recent follow-up, at median age of 15·8 [4·0, 34·4] months; infections were the leading cause. Conclusion: Congenital ZIKV infection is an emerging disease with a varied and incompletely understood spectrum. Continued long-term follow-up is essential to understand longer-term prognosis and to inform future health and educational needs.

Estimating the number of livebirths to Hepatitis C seropositive women in England in 2013 and 2018 using Bayesian modelling.

BACKGROUND: The UK National Screening Committee currently recommends against antenatal screening for Hepatitis C virus (HCV) infection in England due to lack of HCV prevalence data and treatment licensed for use in pregnancy. We aimed to produce regional and national estimates of the number and proportion of livebirths to HCV seropositive women in England in 2013 and 2018. METHODS: A logistic regression model fitted in the Bayesian framework estimated probabilities of HCV seropositivity among 24,599 mothers delivering in the North Thames area of England in 2012 adjusted by maternal age and region of birth. These probabilities were applied to the underlying population structures of women delivering livebirths in England in 2013 and 2018 to estimate the number of livebirths to HCV seropositive women in these years nationally and by region. The Bayesian approach allowed the uncertainty associated with all estimates to be properly quantified. RESULTS: Nationally, the estimated number of livebirths to women seropositive for HCV for England was 464 (95% credible interval [CI] 300-692) in 2013 and 481 (95%CI 310-716) in 2018, or 70.0 (95%CI 45.0-104.1) per 100,000 and 76.9 (95%CI 49.5-114.4) per 100,000 in these years respectively. Regions with the highest estimated number of livebirths to HCV seropositive women in 2013 and 2018 included London with 118.5 and 124.4 and the South East with 67.0 and 74.0 per 100,000 livebirths. CONCLUSION: Few previous studies have investigated HCV among pregnant women in England. These findings complement and supplement existing research by providing national and regional estimates for the number of livebirths to HCV seropositive women in England. Bayesian modelling allows future national and regional estimates to be produced and the associated uncertainty to be properly quantified.

Neurological Short-Term Outcomes of a Cohort of Children Born to Zika Virus-Infected Mothers in Barcelona.

Zika virus (ZIKV) is a vector-borne flavivirus with a known teratogenic effect, yet the full spectrum has not been delineated. Studies on endemic areas tried to characterize the clinical outcomes of ZIKV intrauterine exposure. We aimed to describe early neurodevelopmental outcomes on prenatally ZIKV-exposed children in a non-endemic ZIKV area. This is a prospective observational cohort study conducted from May 2016 to December 2021 at Hospital Universitari Vall d'Hebron in Barcelona, Catalonia, Spain. We monitored for up to 24 months 152 children extracted from a pregnant women cohort with suspected ZIKV infection; eleven women (11/150; 7.3%) fulfilled the criteria for a confirmed ZIKV infection. Among the 152 children included, we describe two cases of congenital ZIKV syndrome (CZS) born from women with a confirmed ZIKV infection. Additionally, we describe five cases of other potentially ZIKV-related outcomes (OPZROs), all with normal birth cranial circumference and born to women with probable ZIKV infection. The low exposed prevalence of adverse outcomes in asymptomatic children at birth in a non-endemic area suggests that close follow-up should be addressed by primary care pediatricians instead of pediatric specialists. Further studies are needed to assess the effects of ZIKV intrauterine exposure beyond two years of life.

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi.

Background: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. Methods: Data were collected from a prospective cohort of infants HIV-exposed aged 1-6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi's Prevention of Mother-to-Child Transmission of HIV Programme (2014-2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P < 0.1. Results: A total of 1,206 singleton CHEU and their mothers were enrolled and 563 completed the follow-up through 24 months of age. Moreover, 48% of CHEU were exposed to ART from conception, 40% from first/second trimester, and 12% from third trimester/postpartum. At enrollment, 12% of infants had low birthweight (LBW), 98% had been breastfed in past 7 days, and 57% were enrolled in an HIV care clinic. CHEU growth trajectories demonstrated cohort-wide growth faltering after the age of 12 months. Of 788 and 780 CHEU contributing to WAZ and LAZ multivariable models, respectively, there was no evidence of differences in mean WAZ or LAZ among those exposed from conception or first/second trimester vs. third trimester/postpartum and no evidence of a difference in WAZ or LAZ rate of change by timing of ART exposure (all interactions P > 1.0). Conclusion: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life.

Detection of Potential Arbovirus Infections and Pregnancy Complications in Pregnant Women in Jamaica Using a Smartphone App (ZIKApp): Pilot Evaluation Study.

BACKGROUND: There is growing evidence of the benefits of mobile health technology, which include symptom tracking apps for research, surveillance, and prevention. No study has yet addressed arbovirus symptom tracking in pregnancy. OBJECTIVE: This study aimed to evaluate the use of a smartphone app (ZIKApp) to self-report arbovirus symptoms and pregnancy complications and to assess compliance with daily symptom diaries during pregnancy in a cohort of women in an arbovirus-endemic, subtropical, middle-income country (Jamaica). METHODS: Pregnant women aged ≥16 years, having a smartphone, and planning on giving birth at the recruiting center were enrolled between February 2020 and July 2020. ZIKApp comprised a daily symptom diary based on algorithms to identify potential episodes of arbovirus infection and pregnancy complications. Sociodemographic, epidemiological, and obstetric information was collected at enrollment, with additional review of medical records, and users' perception was collected through an exit survey. Descriptive analyses and logistic regression analysis of possible factors associated with diary adherence were performed. RESULTS: Of the 173 women enrolled, 157 (90.8%) used ZIKApp for a median duration of 155 (IQR 127-173) days until pregnancy end, 6 (3.5%) used the app for <7 days, and 10 (5.8%) exited the study early. For each successive 30-day period from enrollment up to 150 days after enrollment, of these 157 women, 121 (77.1%) to 129 (82.2%) completed their daily symptom diary; 50 (31.8%) to 56 (35.7%) did so on the same day. Overall, 31.8% (50/157) of the women had good adherence to diary reporting (ie, they completed the task on the same day or 2 to 3 days later for ≥80% of the days enrolled). There were 3-fold higher odds of good adherence for participants aged >34 years versus those aged 25 to 29 years (adjusted odds ratio 3.14, 95% CI 1.10-8.98) and 2-fold higher odds for women with tertiary versus secondary education (adjusted odds ratio 2.26, 95% CI 1.06-4.83). Of the 161 women who ever made a diary entry, 5454 individual symptom reports were made (median 17 per woman; IQR 4-42; range 0-278); 9 (5.6%) women reported symptom combinations triggering a potential arbovirus episode (none had an adverse pregnancy outcome) and 55 (34.2%) reported painful uterine contractions or vaginal bleeding, mainly in the month before delivery. Overall, 51.8% (71/137) of the women rated the app as an excellent experience and were less likely to be poor diary adherers (P=.04) and 99.3% (138/139) reported that the app was easy to understand and use. CONCLUSIONS: This pilot found a high adherence to ZIKApp. It demonstrated the feasibility and usability of the app in an arbovirus-endemic region, supporting its future development to contribute to surveillance and diagnosis of arbovirus infections in pregnancy and to optimize maternal care.