Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia

Hydroxyurea is FDA-approved and now increasingly used for children with sickle cell anemia (SCA), but dosing strategies, pharmacokinetic (PK) profiles, and treatment responses for individual patients are highly variable. Typical weight-based dosing with step-wise escalation to maximum tolerated dose (MTD) leads to predictable laboratory and clinical benefits, but often takes 6 to 12 months to achieve. The Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154) was a single-center study designed to prospectively validate a novel personalized PK-guided hydroxyurea dosing strategy with a primary endpoint of time to MTD. Enrolled participants received a single oral 20 mg/kg dose of hydroxyurea, followed by a sparse PK sampling approach with three samples collected over three hours. Analysis of individual PK data into a population PK model generated a starting dose that targets the MTD. The TREAT cohort (n = 50) was young, starting hydroxyurea at a median age of 11 months (IQR 9-26 months), and PK-guided starting doses were high (27.7 ± 4.9 mg/kg/d). Time to MTD was 4.8 months (IQR 3.3-9.3), significantly shorter than comparison studies (p < 0.0001), thus meeting the primary endpoint. More remarkably, the laboratory response for participants starting with a PK-guided dose was quite robust, achieving higher hemoglobin (10.1 ± 1.3 g/dL) and HbF (33.3 ± 9.1%) levels than traditional dosing. Though higher than traditional dosing, PK-guided doses were safe without excess hematologic toxicities. Our data suggest early initiation of hydroxyurea, using a personalized dosing strategy for children with SCA, provides laboratory and clinical response beyond what has been seen historically, with traditional weight-based dosing.     

Influenza surveillance in Middle East,North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

The Middle‐East and Africa Influenza Surveillance Network (MENA‐ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA‐ISN countries. Data were presented at the 8th MENA‐ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA‐ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA‐ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.     

Vascular factors in diabetic neuropathy

Summary Despite considerable research we still do not have a comprehensive explanation for the pathogenesis of diabetic neuropathy. Although chronic hyperglycaemia is almost certainly involved, it is not known whether the primary pathology is metabolic, microvascular, or an interaction between the two. Hyperglycaemia-induced polyol pathway hyperactivity associated with nerve sorbitol accumulation and myo-inositol depletion may play a part in the genesis of diabetic neuropathy. The case for microvascular disease in diabetic neuropathy is now strong. Fibre loss in human sural nerve is multifocal, suggesting ischaemia. The degree of vessel disease has been related to the severity of neuropathy. People with chronic obstructive pulmonary disease develop the so called hypoxic neuropathy in which similar microvascular changes occur as in diabetic neuropathy. In rats with experimental diabetic neuropathy nerve blood flow is reduced and oxygen supplementation or vasodilator treatment improved the deterioration in conduction velocity and nerve blood flow. Similarly, in human diabetic neuropathy, there is impaired nerve blood flow, epineurial arterio-venous shunting and a reduction in sural nerve oxygen tension. At what stage during the development of nerve damage these changes occur is yet to be determined.Abbreviations RICF resistance to ischaemic conduction failure     

Helicobacter pylori infection in endoscopic biopsy specimens of gastric cancer: a preliminary evaluation in a high risk population of kashmir valley

Objective: The aim of the present study was to assess the prevalence of Helicobacter pylori (H. pylori) infection in Kashmiri patients with gastric cancer and to compare this with a matched control population.Methods: Fifty patients with gastric cancer and thirty age/sex matched controls were included in the study. All the subjects were hailing from Kashmir Valley. For detection of H. pylori, biopsy specimens were used both from cases and controls.Results: An insignificant association was shown between H. pylori and both intestinal and diffuse type of gastric cancer.Conclusions: The data provides support against the significant association between H. pylori and gastric cancer in this part of world, a place where the age standardized incidence of gastric cancer is alarmingly high. We conclude that other factors like personal and special dietary habits of Kashmiri population may be more important for the development of gastric cancer.     

Helicobacter pylori Infection in Various ABO Blood Groups of Kashmiri Population

Aim: This study was carried out to assess the prevalence of Helicobacter pylori infection in various ABO blood groups of people of Kashmir.Method: The study comprised 80 individuals - 50 peptic ulcer patients (whose disease was diagnosed by endoscopy) and 30 asymptomatic volunteers. Every subject's blood group and Rhesus status was determined by standard serological tests. Helicobacter pylori infection was diagnosed by three different methods viz., one minute endoscopy room test (urease test), Gram staining and by histology. The detection of Helicobacter pylori by histological examination using Giemsa staining was taken as the 'gold standard' for the presence of Helicobacter pylori infection.Results: Out of 80 individuals, 67 were males and 13 females aged between 18-65 years. The majority of peptic ulcer patients had blood group 'O' (n = 28.56%). The prevalence of Helicobacter pylori infection amongst peptic ulcer patients was 76%. There was no difference in Helicobacter pylori positivity in various blood groups.Conclusion: Blood group 'O' though a risk factor for peptic ulcer (Duodenal ulcer) is not a risk factor for acquiring Helicobacter pylori infection.