Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be ...determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions.
From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System.
The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death.
We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.
Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) ...services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis.
We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy.
The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01).
These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.
Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis ...that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28+5 (24+4–32+1) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24–27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal–social, hearing–language, eye–hand coordination and performance scales at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye–hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and provide a biomarker for therapeutic or mechanistic studies of preterm brain injury.
Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage ...(IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda.
This is a prospective cohort study of neonates with birthweights of ≤2000 g admitted to a neonatal unit (NU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival.
Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) < 32 weeks and resuscitation in the NU increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH.
In this resource limited NU in eastern Uganda, more than a third of neonates born weighing ≤2000 g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation and need for resuscitation after admission to the NU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.
Recent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker ...test for the identification of individuals at risk of developing schizophrenia based on multiplex immunoassay profiling analysis of 957 serum samples. First, we conducted a meta-analysis of five independent cohorts of 127 first-onset drug-naive schizophrenia patients and 204 controls. Using least absolute shrinkage and selection operator regression, we identified an optimal panel of 26 biomarkers that best discriminated patients and controls. Next, we successfully validated this biomarker panel using two independent validation cohorts of 93 patients and 88 controls, which yielded an area under the curve (AUC) of 0.97 (0.95-1.00) for schizophrenia detection. Finally, we tested its predictive performance for identifying patients before onset of psychosis using two cohorts of 445 pre-onset or at-risk individuals. The predictive performance achieved by the panel was excellent for identifying USA military personnel (AUC: 0.90 (0.86-0.95)) and help-seeking prodromal individuals (AUC: 0.82 (0.71-0.93)) who developed schizophrenia up to 2 years after baseline sampling. The performance increased further using the latter cohort following the incorporation of CAARMS (Comprehensive Assessment of At-Risk Mental State) positive subscale symptom scores into the model (AUC: 0.90 (0.82-0.98)). The current findings may represent the first successful step towards a test that could address the clinical need for early intervention in psychiatry. Further developments of a combined molecular/symptom-based test will aid clinicians in the identification of vulnerable patients early in the disease process, allowing more effective therapeutic intervention before overt disease onset.
We constructed self-reported pre-exposure prophylaxis (PrEP) cascades and explored factors associated with and barriers to PrEP use to inform efforts to support PrEP use among young women who sell ...sex.
Using self-reported data from HIV-negative young women who sell sex enrolled into a cohort study using respondent-driven sampling in Zimbabwe, we constructed PrEP cascades assessing knowledge of, ever offered, ever used, and current PrEP use in 2017 and 2019. We used logistic regression to examine factors associated with PrEP use by 2019. Through qualitative interviews with 43 women enrolled in the cohort, we investigated barriers to PrEP use.
At enrollment, 50% of women had heard of PrEP, 12% had ever been offered PrEP, and 7% ever used PrEP. Over time, all cascade domains: 96% of women had heard of and 55% reported an active offer of PrEP. Among women retained in the study in 2019 (56%; n = 538), 34% ever took PrEP by 2019. PrEP use was associated with, at enrollment, reporting more clients in the past month (10+: 45% vs 1-3: 27% adjOR = 1.71 95% CI: 1.06 to 2.76), duration of selling sex (24% <2 years vs 38% 2-3 years; adjOR = 0.51 95% CI: 0.32 to 0.83), and having visited a female sex worker program in the past 12 months (55% vs 27%; adjOR = 2.92 95% CI: 1.91 to 4.46). Qualitative interviews revealed fear of disclosing sex work, HIV-related/ART-related stigma, and (opportunity) costs of accessing PrEP as barriers to use.
PrEP use was associated with factors known to increase HIV risk. Fear of stigma, disclosure, and supply-side barriers need to be addressed to increase women's ability to use PrEP.
Aim
To investigate whether motor performance in school‐age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18‐month developmental ...scores and to explore relationships between school‐age motor and cognitive performance.
Methods
Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children‐2 (MABC‐2) and the Wechsler Intelligence Scale for Children (WISC‐IV). Associations between MABC‐2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18‐month Bayley‐III scores and WISC‐IV scores were explored.
Results
Eleven of the 29 (38%) children had MABC‐2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio‐economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC‐2 scores ≤15th centile. MABC‐2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01).
Conclusion
A third of cooled children without CP had MABC‐2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley‐III. Most children with low MABC scores needed support at school. Sub‐optimal MABC‐2 scores indicate need for detailed school‐age cognitive evaluation.
HIV stigma can inhibit uptake of HIV testing and antiretroviral therapy as well as negatively affect mental health. Efforts to reduce discrimination against people living with HIV (LWH) have ...contributed to greater acceptance of the infection. Female sex workers (FSW) LWH may experience overlapping stigma due to both their work and HIV status, although this is poorly understood. We examined HIV and sex-work stigma experienced by FSW LWH in Zimbabwe. Using the SAPPH-IRe cluster-randomised trial baseline survey, we analysed the data from 1039 FSW self-reporting HIV. The women were recruited in 14 sites using respondent-driven sampling. We asked five questions to assess internalised and experienced stigma related to working as a sex worker, and the same questions were asked in reference to HIV. Among all FSW, 91% reported some form of sex-work stigma. This was not associated with sociodemographic or sex-work characteristics. Rates of sex-work stigma were higher than those of HIV-related stigma. For example, 38% reported being "talked badly about" for LWH compared with 77% for their involvement in sex work. Those who reported any sex-work stigma also reported experiencing more HIV stigma compared to those who did not report sex-work stigma, suggesting a layering effect. FSW in Zimbabwe experience stigma for their role as "immoral" women and this appears more prevalent than HIV stigma. As HIV stigma attenuates, other forms of social stigma associated with the disease may persist and continue to pose barriers to effective care.
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