The differential effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on seizure frequency in patients with drug-resistant epilepsy – A Randomized, double-blind, placebo-controlled trial

Abstract The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with DRE was investigated. Methods: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n=99) DRE patients, aged 5-16 (n=85) and 17-45 (n=14). After randomization, patients were given two, four or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n=33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n=33) or placebo (high oleic acid sunflower oil, n=33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients’ total count of seizures per month. The treatment effects on seizure incidence rate ratio was tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure and number of AEDs combinations used at enrollment. Results: Fifty-nine patients (n=59) completed the study (59.6%).The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender and seizure type adjusted seizure incidence rate ratios (IRRs) of the EPA and DHA groups compared with the placebo were 0.61 (CI= 0.42-0.88, p=0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p= 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p=0.56). Both treatment groups had a significantly higher number of seizure-free days compared to placebo (p<0.05). Significance: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family

Abstract Background Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. Case presentation Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members. Conclusion This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients’ phenotype). Therefore this variant can be currently annotated as “pathogenic”. This is the first study to report mutations in PLA2G6 gene in patients from Sudan

Parkinsonism Relat Disord

Background: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson’s disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan. Materials and methods: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCAintron1 was performed as described earlier. Results: Of the fourteen analyzed CpGs of SNCAintron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P–values improved, when sporadic cases were excluded from the analysis. Conclusion: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCAintron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research