Growth patterns in a cohort of very low birth weight infants in Johannesburg: a retrospective review

Thesis MMed (Paediatrics), Faculty of Health Sciences, University of the WitwatersrandINTRODUCTION: Improved survival of VLBW infants is raising several management issues. An example is that of growth and growth monitoring. AIM OF THE STUDY: To assess the growth of a cohort of VLBW infants born at CMJAH from term CGA to 20 months CGA. METHODS: A retrospective chart review was conducted on 139 VLBW infants (birth weight ≤ 1500g) born at CMJAH between 1 July 2006 and 28 February 2007. RESULTS: Comparison with a term growth reference showed initial growth failure followed by gradual catch up growth but with persistent deficits in length for age. Comparison with international VLBW references showed similar growth for weight and head circumference for age but with deficits in length for age. Growth parameters of the study sample were similar to those of other South African VLBW infants. CONCLUSION: Growth and growth monitoring in VLBW infants is complicated by characteristic growth patterns, high associated morbidity, controversies surrounding ideal growth and lack of an ideal growth reference. Significant deficits in length for age in the study sample may have been due to the large proportion of infants born SGA and the high prevalence of stunting in South African children. Current recommendations for growth monitoring of VLBW infants include the use of a VLBW reference up to two years CGA followed by a term growth reference thereafte

Does vocabulary influence word recognition and reading comprehension through set for variability? : a thesis presented in partial fulfilment of the requirements for the degree of Master of Education at Massey University, Manawatū, New Zealand

Vocabulary is recognised as a key contributor to literacy development and comprehension. Children cannot make meaning from text if they lack the vocabulary to support what is being read. This study investigated the independent contribution of vocabulary to word recognition, and whether the contribution was direct or indirect through set for variability. A second aim of the study was to determine if a direct relation exists between vocabulary knowledge and reading comprehension. Unpublished data from the longitudinal study (Chapman, Arrow, Tunmer, & Braid, 2016) were analysed to find predictive links between vocabulary and later reading outcomes, for a cohort of 374 5-year-old children in New Zealand primary schools. The results identified that word recognition and vocabulary both directly contributed to reading comprehension for these children in the middle of their second year at school. Word recognition explained a greater amount of the shared variance of reading comprehension in the middle of Year 2 as the children were at the stage of still trying to read a range of unfamiliar words. Set for variability was found not to directly contribute to reading comprehension when word recognition was added to the model. This finding suggests that set for variability mediates the relationship between vocabulary and word recognition but not for overall reading comprehension. In terms of practical teaching, it is suggested that language comprehension abilities should be acquired alongside the development of word recognition skills

Serum 1,3-βD-Glucan assay in the diagnosis of invasive fungal disease in neonates

Invasive fungal disease is a significant cause of morbidity and mortality in the neonate. The current study aims to assess the 1, 3-βD-Glucan (BG) assay in a prospective analysis in neonates with suspected fungaemia. A multicentre, prospective cohort study was conducted in Johannesburg, South Africa. The study included 72 neonates with clinically suspected late onset sepsis who were at high risk of fungaemia. A BG assay was performed on each patient and correlated with a sepsis classification based on the full blood count, C-reactive protein and blood culture results as no fungaemia, possible fungaemia, probable fungaemia or definite fungaemia. Sensitivity and specificity of the BG assay at levels of 60 pg/mL are 73.2% and 71.0% respectively and at levels of 80 pg/mL are 70.7% and 77.4% respectively. Positive and negative predictive values at 60 pg/mL are 76.9% and 66.7% respectively and at 80 pg/mL are 80.6% and 66.7% respectively. The area under the receiver operating curve is 0.753. The BG assay is a useful adjunct to the diagnosis of invasive fungal disease in neonates. It does, however, need to be considered in the context of the clinical picture and supplementary laboratory investigations

Umbilical cord interleukin-6 predicts outcome in very low birthweight infants in a high HIV-burden setting: a prospective cohort study

Objectives South Africa has a double burden of high neonatal mortality and maternal HIV prevalence. Common to both is a proinflammatory in utero and perinatal milieu. The aim of this study was to determine cytokine profiles in HIV exposed (HE) and HIV unexposed (HU) very low birthweight (VLBW) infants and to determine whether these were associated with predischarge outcomes. Design Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019. Patients Inborn infants with birth weight of <1500 g were enrolled and cord blood was collected for interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) assays. Participants provided informed consent and ethics approval was obtained. Outcome measures The primary outcome was umbilical cord cytokine levels according to maternal HIV status. Secondary outcomes included death and/or serious neonatal infection, necrotising enterocolitis, intraventricular haemorrhage, periventricular leucomalacia, chronic lung disease and haemodynamically significant patent ductus arteriosus before discharge. Results A total of 279 cases were included with 269 cytokine assays performed on 122 HEs and 147 HUs. Median IL-6 levels were 53.0 pg/mL in HEs and 21.0 pg/ mL in HUs (p=0.07). Median TNF-α levels were 7.2 pg/ mL in HEs and 6.5 pg/mL in HUs (p=0.6). There was significantly more late-onset sepsis in the HE group compared with the HU group (41.2% vs 27.9%) (p=0.03). IL-6 levels were significantly higher for those with any adverse outcome (p=0.006) and death and/or any adverse outcome (p=0.0001). TNF-α levels did not differ according to predischarge outcomes. Conclusion There is no significant difference in IL-6 and TNF-α levels in cord blood of HE compared with HU VLBWs. However, IL-6 levels are significantly higher in VLBWs with adverse predischarge outcomes, and VLBW HEs are at increased risk of adverse predischarge outcomes compared with HUs, particularly late-onset sepsis

Umbilical cord interleukin-6 predicts outcome in very low birthweight infants in a high HIV-burden setting: a prospective cohort study

Objectives South Africa has a double burden of high neonatal mortality and maternal HIV prevalence. Common to both is a proinflammatory in utero and perinatal milieu. The aim of this study was to determine cytokine profiles in HIV exposed (HE) and HIV unexposed (HU) very low birthweight (VLBW) infants and to determine whether these were associated with predischarge outcomes. Design Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019. Patients Inborn infants with birth weight of <1500 g were enrolled and cord blood was collected for interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) assays. Participants provided informed consent and ethics approval was obtained. Outcome measures The primary outcome was umbilical cord cytokine levels according to maternal HIV status. Secondary outcomes included death and/or serious neonatal infection, necrotising enterocolitis, intraventricular haemorrhage, periventricular leucomalacia, chronic lung disease and haemodynamically significant patent ductus arteriosus before discharge. Results A total of 279 cases were included with 269 cytokine assays performed on 122 HEs and 147 HUs. Median IL-6 levels were 53.0 pg/mL in HEs and 21.0 pg/ mL in HUs (p=0.07). Median TNF-α levels were 7.2 pg/ mL in HEs and 6.5 pg/mL in HUs (p=0.6). There was significantly more late-onset sepsis in the HE group compared with the HU group (41.2% vs 27.9%) (p=0.03). IL-6 levels were significantly higher for those with any adverse outcome (p=0.006) and death and/or any adverse outcome (p=0.0001). TNF-α levels did not differ according to predischarge outcomes. Conclusion There is no significant difference in IL-6 and TNF-α levels in cord blood of HE compared with HU VLBWs. However, IL-6 levels are significantly higher in VLBWs with adverse predischarge outcomes, and VLBW HEs are at increased risk of adverse predischarge outcomes compared with HUs, particularly late-onset sepsis

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society