Dinesh Nayak

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

Relationship between neurological outcome and early oxidative changes in erythrocytes in head injury patients.

Abstract Background: Experimental data indicate that destructive oxidative events reach their peak within the first 24 h after trauma in head injury (HI) and that brain damage occurring due to this impact can be the cause of death or irreversible permanent disabilities in affected patients. Methods: Venous blood samples were obtained from 50 HI patients within 24 h of trauma onset and from 30 age- and sex-matched normal controls (NC). Patients were divided into three different neurological outcome groups: those who died within 10 days of trauma (D), and those with severe neurological deficits (SD) or mild/no neurological deficits (MD) at 90 days after trauma. Early oxidative changes in erythrocytes were assessed by estimating an indicator of lipid peroxidative damage – thiobarbituric acid-reactive substances (TBARS) – and antioxidants [reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity]. Results: In the D group, erythrocyte TBARS levels were significantly higher compared to the NC, SD and MD groups (p<0.001); GSH levels were significantly lower compared to the NC (p<0.001) and MD (p<0.01) groups and SOD activity was significantly higher than in the NC (p<0.01) and MD (p<0.01) groups. In the SD group, TBARS levels were significantly higher than in the NC (p<0.001) and MD (p<0.05) groups; GSH levels were significantly lower than in the NC (p<0.001) and MD (p<0.01) groups and SOD activity was higher compared to the NC and MD (p<0.01) groups. In the MD group, TBARS levels were significantly higher and GSH levels significantly lower compared to the NC group (p<0.001). However, we did not observe any significant change in SOD activity compared to the NC group. Conclusions: These findings indicate that early oxidative changes may reflect the severity of neurological insult and provide an early indication of patient outcome in traumatic HI. Clin Chem Lab Med 2007;45:629–33.

Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients

Abstract Background: Oxidative stress is said to strongly influence the neurological recovery of patients following a severe head injury. Estimation of the markers of oxidative stress in the blood of such patients can hence aid in predicting the prognosis of head injury. Methods: Erythrocyte thiobarbituric acid-reactive substances (TBARS) and plasma ceruloplasmin (CP) levels were estimated in 24 severe head-injury patients on days 1, 7 and 21 of the post-traumatic period and compared with levels in 25 healthy age- and sex-matched controls. These parameters reflecting oxidative stress status were related to the Glasgow Coma Scale (GCS) scores of patients noted at the same time points of the study period. Results: Lipid peroxidation as indicated by increased levels of erythrocyte TBARS remained significantly elevated in severe head injury patients compared to controls on day 1 (p<0.001), day 7 (p<0.001) and 21 (p<0.001) of the post-traumatic period. Plasma CP levels remained significantly elevated (p<0.001) at these three time points compared to controls. The significant decrease in lipid peroxidation products (p<0.01) and significant increase in CP levels (p<0.001) on day 21 compared to day 1 in head injury patients correlated well with the significant improvement in GCS scores of patients on day 21 compared to day 1 (p<0.05). Conclusion: The above results could account for the adaptation of the study patients to severe oxidative stress, as evidenced by their clinical recovery trend during the study period.

Relationship between markers of lipid peroxidation, thiol oxidation and Glasgow coma scale scores of moderate head injury patients in the 7 day post-traumatic period

Abstract Objective: Epidemiologic works reveal that moderate head injury (MHI) is more frequent and a substantial number of these patients develop complications resulting in neurological disabilities. Reactive oxygen species (ROS) play a major role in post-traumatic neuronal damage following traumatic head injury. Thus, the current study analysed the post-traumatic changes in the erythrocyte markers of oxidative damage and the relationship between these parameters and Glasgow coma scale (GCS) scores of MHI patients during the 7 day study period. Methods: Peripheral venous blood samples were taken at the time of hospital admission (d1 of injury) and on d7 from 25 MHI patients (admission GCS score>8). These were compared with samples from 25 healthy individuals (normal controls, NC). GCS scores were recorded at the same time points of the study period. Erythrocyte lipid peroxidation (LP) and thiol oxidation levels were estimated and compared with that of NC. The relationship between GCS scores and erythrocyte markers were also studied. Results: Erythrocyte thiobarbituric acid reactive substance (TBARS) levels reflecting lipid peroxidative damage remained significantly elevated at both time points of the study period in MHI patients as compared to NC (p<0.001). There was a significant decrease in the level of non-protein thiols in MHI patients as compared to NC (p<0.01) at the same time points of the study. However, on d7 there were no further significant changes in the markers of oxidative damage in MHI patients as compared to on d1. Conclusion: These findings suggest that a condition of oxidative stress occurs during the entire post-traumatic period in MHI patients and the utility of markers of oxidative damage in the prognosis of head injury needs to be addressed in further works.

Effectiveness of a training program for bleeding disorders among accredited social health activists in Udupi District, Karnataka, India

Hemophilia and other bleeding disorders are underreported and cause significant morbidity and mortality in resource‐constrained countries. Training and the creation of awareness among accredited social heath activists (ASHAs) will aid in the early detection of bleeding disorders at the community level.

Knowledge among mothers’ of children and youth with hemophilia-A cross sectional survey at a hemophilia center

Introduction: Hemophilia is a genetic disease caused by deficiency of factor VIII or IX. Awareness about the disease condition among parents and children also is as important to manage the disease effectively. Objectives: To assess the knowledge on hemophilia among mothers’ of children with hemophilia and youth with hemophilia. Methodology: A cross sectional survey was conducted at hemophilia center(Manipal, Karnataka). In total, 23 mothers’ of children and 27 youth with moderate and severe hemophilia were included. The participants were selected based on purposive sampling. Approval was taken from the ethical committee. Demographic proforma and knowledge questionnaire was used to collect the data. The data was analyzed using SPSS 16.0 version. Results: The mean age of the participants were 13.68 years. Out of 50 participants 42 had moderate and 8 had severe hemophilia. Moderate knowledge was found among 43.5% of mothers’ and 66.7% of youth with hemophilia. Conclusion: This study shows that mothers’ knowledge on hemophilia is limited and highlights the importance of continual education of parents and youth about their disease.

Effectiveness of a comprehensive educational programme for Accredited Social Health Activists (ASHAs) to identify individuals in the Udupi district with bleeding disorders: A community-based survey

The awareness and knowledge on bleeding disorders is generally poor among the rural population. Accredited Social Health Activists (ASHAs) serve as the facilitators between the rural community and the health care system. Training of ASHAs in screening of rural population for early identification of bleeding disorders can enable prompt referral, timely detection and management of bleeding disorders.

A portrayal of childhood injury among under- five year children

Introduction:Children and injuries are always closely associated. Injuries to children irrespective of its seriousness will affect the whole family function. One of the major reasons for childhood morbidity and mortality are injuries. Method: A cross sectional house to house survey was conducted in Udupi Taluk to identify the major types of childhood injuries. The study also tried to find the association between the age of the child and the common injuries.Results:The present study used a sample subject of 2040 for the survey. The mean age of children included in the study were 2.60 (SD + 1.16) years. Majority of children included in the survey were males 52.5%. The overall injury identified in survey was 14%. Fall from stairs (92%), burn with hot water/food (41%), injury with a sharp knife (72%), accidental ingestion of medicine (3%), injury during play (94%) and foreign body in ear and nose (79%) were identified as the most common injuries among children of 2 to 5 years.Conclusion:This article establishes the need for a detailed prevalence survey. A detailed survey will help in planning an intervention for caregivers which can reduce the injuries in children.