Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Presentation, management and short-term outcomes of extradural spinal tumours at the University Teaching Hospital in Lusaka, Zambia

Objectives: To investigate the clinical presentation of patients with extradural spinal tumours and establish the factors that determined the treatment they received and outline the outcomes of that treatment at the University Teaching Hospital between January 2013 and December 2016.Material and Methods: This was a retrospective study of the presentation, management and shortterm outcome of extradural spinal tumours at the University Teaching Hospital. A questionnaire was used to obtain data from patients' hospital records. Data was analysed using Microsoft Excel and the Statistical Package for Social Sciences version 25 software.Results: Of the 62 patients in the study, 34 were female and 28 male. The age range was 14 to 87 years, with a mean of 55.03. Backache (93.8%), Limb weakness (91.9%), loss of sensation (50%), urine and stool incontinence (43.5% and 41.9% respectively), back deformity (11.3%), night pain (85.5%), weight loss(67.7%), poor appetite (61.3%), fever (35.5%) and night sweats(29%) were common symptoms. Sixty-eight percent of patients were bedridden. Visual Analogue Scale scores were  greater than 5 in 84% of patients. A muscle power grade of 3 or less (n=48), impaired muscle tone (n=38), abnormal reflexes (n=52), presence of a sensory level(n=37) and back deformity (n=17) were common signs. Plain radiography, Computed Tomography Scans, Magnetic Resonance Scans and Tecnetium Bone scans were done in 60, 35, 17 and 2 patients respectively. The commonest surgical host category was A (64%). Secondary Extradural Spinal Tumours comprised 82% while 18% were primary. Surgery was done in 14 patients with 1 failing to afford implants. Forty-eight received nonsurgical treatment. Nineteen percent of patients had improved pain scores but the rest remained the same or worsened after treatment. Complications included decubitus ulcers, Urinary Tract Infection, Deep Veinous Thrombosis, pneumonia, sepsis and joint stiffness. Fourty patients died and eighteen patients were lost to follow-up.Conclusions: The ages of patients followed normal distribution with female to male ratio of 1.2 to 1. Most patients presented with symptoms and signs of advanced disease. The type of extradural spinal tumour, stage of disease, completeness of diagnostic workup, availability of implants, need for tissue diagnosis, type of surgical host and availability of nonsurgical treatment modality determined the choice of treatment. Poor outcomes in quantity and quality of life are a reflection of the late presentation, delayed diagnosis, lack of resources and difficulty of  treating these tumours. Extradural spinal tumours are not uncommon and cause significant morbidity and mortality in those affected