Prophylactic bypassing agent use before and during immune tolerance induction in patients with haemophilia A and inhibitors to FVIII.

The development of high-titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high-titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI), utilizing repeated infusions of FVIII, is an effective therapeutic approach to eliminating inhibitory antibodies. This strategy can eradicate FVIII inhibitors, so that FVIII-specific tolerance is induced. However, patients undergoing ITI are still vulnerable to the development of serious and/or repeated bleeding events. The efficacy of bypassing agents in preventing bleeding episodes has been widely proven in patients with HA and inhibitors to FVIII. Evidence suggests that reducing bleeding during ITI can also shorten the time to tolerance. There are concerns with the use of bypassing agents, including the cost of treatment, short half-life, management of non-responders and the risk of thrombosis. Despite these concerns, and the still limited evidence from prospective studies and consensus reports, the use of prophylaxis with bypassing agents during ITI has been gaining support. This review presents a rationale and current data supporting the use of prophylactic bypassing agents as effective and safe therapies to reduce the incidence of joint bleeding due to inhibitors and improve quality of life in patients with HA undergoing ITI.

Validation of the Haemophilia & Exercise Project-Test-Questionnaire (HEP-Test-Q)-An instrument for the assessment of subjective physical functioning in children with haemophilia.

INTRODUCTION: Contemporary haemophilia management recommends sport and physical activity in children with haemophilia. Assessment of subjective physical functioning requires standardized and validated instruments. AIMS: To adapt and psychometrically test the adult Haemophilia & Exercise Project-Test-Questionnaire (HEP-Test-Q) for children (aged 6-17 years). METHODS: In discussion rounds with children, single items of the adult HEP-Test-Q were reformulated to make them understandable without changing the item concept. The validation of the child-adapted version in children with haemophilia (n = 228) included pre-testing with feasibility testing, cognitive interviewing (n = 34), pilot-testing of the revised version in the EIS Study (n = 67) and field-testing in the SO-FIT Study (n = 127). RESULTS: Pre-testing revealed a completion time of 8.2 ± 4.1 minutes and children liked the instrument. Cognitive interviews demonstrated that most items were easy to understand; 9 items were reformulated. Pilot-testing demonstrated good psychometric characteristics in terms of reliability (α = .94 Total Score) and validity. Convergent validity testing showed moderate correlations with the Haemo-QoL (r = -.491), but low correlations with the Petrini Score (r = -.293). Known groups' validity revealed significant differences in clinical subgroups; chronic pain (P < .002) and target joints (P < .021). Field-testing confirmed psychometric characteristics; Cronbach's alpha ranged from α = .80 ("endurance") to α = .94 (Total Score). The child-adapted HEP-Test-Q showed moderate correlations with the PedHAL (r = .634, P < .0001) and the Haemo-QoL SF (r = -.575, P < .0001). Known groups' validity testing proved that the HEP-Test-Q could discriminate between clinical subgroups. CONCLUSION: The child-adapted HEP-Test-Q is a short, practical and acceptable instrument for the assessment of subjective physical functioning. Outcomes can be compared to adults because item concepts are identical to the adult version.

Pattern of bleeding in a large prospective cohort of haemophilia A patients: A three-year follow-up of the AHEAD (Advate in HaEmophilia A outcome Database) study.

INTRODUCTION: Outcome data on treatment of patients with haemophilia A spanning several years of real-world evidence collection are currently very limited. AIM AND METHODS: The global prospective long-term Advate® Haemophilia A Outcome Database (AHEAD) cohort study collects real-world data from patients with severe and moderate haemophilia. We report an interim data read-out after three years of observation. RESULTS: A total of 522 patients were enrolled from 21 countries: 334 completed year 1 follow-up, 238 completed year 2 and 136 completed year 3, with an overall follow-up of 811 patient-years. Median annual bleeding rates (ABR) were 1.7 in the prophylaxis group and 8.9 in the on-demand group at year 1 visit, 1.6 and 13.0, respectively, at year 2 visit and 2.2 and 10.3, respectively, at year 3 visit. Moreover, about 42% of patients on prophylaxis vs 12% of patients on on-demand had zero annual joint bleeding rates (AJBR). Effectiveness of prophylaxis and on-demand treatment was deemed excellent/good in the majority of cases. Octocog alfa (Advate® ) was well tolerated. The inhibitors that developed in nine patients all disappeared spontaneously. Three patients had been previously exposed to FVIII for ≤50 exposure days (EDs), 3 for >50 EDs and 3 showed a borderline positive inhibitory activity (≤0.6 BU/mL). CONCLUSIONS: These data confirm that the goal of zero bleeds is achievable, although not yet achieved in all patients. Understanding reasons behind the lower response to standard prophylaxis regimens in some patients and personalizing prophylactic treatment may further improve outcome in patients with haemophilia A.

The impact of clinical practice on the outcome of central venous access devices in children with haemophilia.

INTRODUCTION: Central venous access devices facilitate home treatment in boys with haemophilia. These are usually fully implanted lines, referred to as ports. Caregivers are taught to manage the port using sterile techniques and maintaining patency by flushing with saline or heparin solution. National and international guidelines for the home care of ports are lacking. AIM: To evaluate if infection or occlusion rates differ between home care regimens used for ports in children with haemophilia. METHODS: Children with ports were identified from the PedNet registry. Data on the homecare policy were acquired from each centre. To ensure a complete data set for each port, only ports that had been removed were included in the study. Three care groups were defined: 'aseptic non touch technique', 'sterile technique' and 'fully sterile technique'. Outcomes within and between the groups were analysed. RESULTS: A total of 240 children with 352 ports were studied. Insertion occurred at a median age of 1.32 years. The median port duration was 2.94 years with a total of 215 688 port days in children without and 183 852 in children with inhibitors. Infection was the most common cause of port removal (34%); there was no significant difference with infection as reason for removal between the different care groups. Occlusion was not more frequent in centres that did not use heparin. CONCLUSION: Use of sterile gloves and gowns did not reduce the risk of port infection. Using less stringent sterile techniques for accessing ports is easier for caregivers and in addition may have health economic benefits.

Study of physical function in adolescents with haemophilia: The SO-FIT study.

INTRODUCTION: Contemporary haemophilia care demands Patient-Reported Outcomes. SO-FIT is a UK multi-centre study, assessing self-reported function, health-related quality of life (HRQoL) and joint health in boys with severe haemophilia. METHODS: Subjective physical function (PedHAL, HEP-Test-Q) and HRQoL (Haemo-QoL Short Form [SF]) were assessed alongside joint health using the objective Haemophilia Joint Health Score (HJHS v2.1). Demographic and clinical data were collected. RESULTS: Data from 127 boys mean age 12.38 ± 2.5 (range 8-17) treated at 16 sites were analysed. One-hundred-and-thirteen had haemophilia A, 25/9 past/current inhibitor, 124 were treated prophylactically (46.8% primary) and three on-demand. In the preceding 6 months, boys reported median 0 joint bleeds (range 0-8) with a median HJHS score of 1 (range 0-30). Boys reported good physical functioning; HEP-Test-Q (M = 80.32 ± 16.1) showed the highest impairments in the domain "endurance" (72.53 ± 19.1), in PedHAL (M = 85.44 ± 18.9) highest impairments were in the domains "leisure activities & sports" (M = 82.43 ± 23.4) and "lying/sitting/kneeling/standing" (M = 83.22 ± 20.3). Boys reported generally good HRQoL in Haemo-QoL SF SF (M = 22.81 ± 15.0) with highest impairments in the domains "friends" (M = 28.81 ± 30.5) and "sports & school" (M = 26.14 ± 25.1). HJHS revealed low correlations with the Haemo-QoL SF (r = .251, P < .006), the PedHAL (r = -.397, P < .0001) and the HEP-Test-Q (r = -.323, P < .0001). A moderate correlation was seen between HEP-Test-Q and Haemo-QoL SF of r = -.575 (P < .0001) and between PedHAL and Haemo-QoL SFr = -.561 (P < .0001) implying that good perceived physical function is related to good HRQoL. CONCLUSIONS: The SO-FIT study has demonstrated that children with severe haemophilia in the UK report good HRQoL and have good joint health as reflected in low HJHS scores.

Assessment and management of pain in children and adolescents with bleeding disorders: a cross-sectional study from three haemophilia centres.

INTRODUCTION: Pain is a major clinical problem in patients with bleeding disorders. This study aimed to determine the level of pain and how it is managed in children and adolescents with bleeding disorders. METHODS: This cross-sectional study was performed in three haemophilia centres (one in Shiraz and two in London).The data were collected using questions about pain management and Wong-Baker Faces Pain Rating Scale at routine clinical review as well as attendance for bleed treatment in summer 2014. RESULTS: This study indicated no difference among the three haemophilia centres regarding having pain, however, a significant difference was found among them concerning the mean score of pain intensity. Among the 154 subjects, 20.8% had pain on the study day, most reporting moderate levels of pain. The study participant's most frequently described their pain as aching, dull, throbbing and stabbing. Moreover, 84.38% of pain was experienced in joints and the most common painful joints were knees, ankles, elbows, hands and hips. The most common pain relief strategies included factor administration, immobilization and rest, ice packs and analgesia. Pain was significantly associated with disease severity and age. CONCLUSION: As the intensity of pain in on-demand patients was highest, using prophylaxis treatment is suggested. Moreover, adolescent patients reported more pain; giving more self-care information to them and their parents is recommended. Since little evidence was published for pain assessment and management in children and adolescents with bleeding disorders, more research is recommended.

The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center.

INTRODUCTION: Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. AIM: This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. METHODS: The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. RESULTS: ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). CONCLUSION: Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation.

The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia.

BACKGROUND: There is increasing recognition that sport is important for individuals with haemophilia; however, there remains a paucity of data of the importance of this in adults, many of whom already have joint pathology related to childhood bleeds and treatment access. This multicentre, cross-sectional study presents the impact of sport on health-related quality of life (HRQoL), physical performance and clinical outcomes in adults with haemophilia. RESULTS: Fifty adults aged 35.12±14.7 with mild (n = 12), moderate (n = 10), or severe (n = 28) haemophilia A (70%) or B (30%) from four haemophilia centres across the United Kingdom participated in the study. A total of 64% were overweight/obese according to their BMI; median orthopaedic joint scores using the WFH Orthopaedic Joint Score (OJS) were 6 (range 0-48). On a VAS pain scale (range of 0-10), patients reported mean score of 5.66 ± 2.4. 36% of participants reported not doing any sport, mainly due to their physical condition. However, 64% of participants reported undertaking sporting activity including contact sports, mostly twice per week in average 4 h week(-1) . Participating in sport did not have a statistically significant impact on HRQoL; except in the domain 'sport and leisure' of the Haem-A-QoL. Patients doing more sport reported significantly better HRQoL than those doing less sport (P < 0.005). Those doing sport for more than 4 h week(-1) had a significantly better physical performance than patients doing less sport (assessed with Hep-Test-Q). Encouraging physical activity and sport in older patients with haemophilia may have a direct impact on their HRQoL; thus, education about sport activity should be incorporated into routine haemophilia care.

Spotlight on the human factor: building a foundation for the future of haemophilia A management: report from a symposium on human recombinant FVIII at the World Federation of Hemophilia World Congress, Melbourne, Australia on 12 May 2014.

Inhibitor development is the most serious and challenging complication in the treatment of severe haemophilia A. Up to 38% of such patients develop inhibitors with current recombinant factor VIII (rFVIII) products produced in hamster cell lines. Human-cl rhFVIII is a new generation fully sulfated B-domain-deleted FVIII coagulant glycoprotein, which is generated from a human cell line. Thus, there are no non-human epitopes which would be potentially immunogenic. This molecule has significantly higher VWF-binding affinity compared with existing full-length rFVIII produced in hamster cell lines. The development aim of Human-cl rhFVIII is to address the challenges of FVIII inhibitors and frequent infusions during prophylaxis. Human-cl rhFVIII's mean half-life is very comparable to some of the newer products which involve modification of the FVIII molecule to extend the circulating half-life. There are promising data concerning the use of a personalized prophylaxis regimen with Human-cl rhFVIII. Preliminary data indicate a median dosing interval of 3.5 days with 66.7% of the patients on a twice per week or fewer infusions schedule combined with a low bleeding rate and no increased FVIII consumption when compared to standard prophylaxis. No product-specific laboratory assay is required to monitor the coagulation activity for Human-cl rhFVIII. The results of registration clinical trials with Human-cl rhFVIII as well as the ongoing studies in previously untreated patients (NuProtect) and personalized prophylaxis study in previously treated patients (NuPreviq), will be discussed. The manufacturer has received marketing authorization for Human-cl rhFVIII in Europe and Canada under the name Nuwiq(®) and plans to launch it in the USA and globally in 2015.

Wilate use in 47 children with von Willebrand disease: the North London paediatric haemophilia network experience.

Children with von Willebrand disease (VWD) in whom DDAVP is ineffective or contraindicated require treatment with a coagulation factor concentrate containing von Willebrand factor (VWF) and factor VIII (FVIII). The aim of this study was to monitor the safety, efficacy and tolerability of Wilate(®) (a VWF:FVIII concentrate with a 1:1 ratio) used across the North London Paediatric Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years) with type 1 (n = 28), type 2 (n = 7), type 3 (n = 10) and acquired VWS (n = 2) have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU Wilate(®). Analysis of dose and frequency of treatment show expected responses to treatment with mean doses of 55, 50 and 50 IU kg(-1) for bleeds, surgery and prophylaxis respectively. Most bleeds responded to a single treatment. Surgical procedures were covered with clinician approved dosing schedules with 95% (39/41) reported as having excellent or good efficacy. There was no accumulation of FVIII or VWF and no thromboembolic events. This case series confirms the efficacy, safety and tolerability of Wilate(®) in neonates, children and adolescents when used on-demand, prophylactically and in the surgical setting.

Compliance, concordance and adherence: what are we talking about?

Adherence or compliance to prescribed treatment regimens is an important and much debated area of haemophilia care. Many patients are labelled as 'non-adherent' because they don't do what we say in terms of self- treatment and factor administration. However, do we engage patients in developing mutually acceptable treatment programmes which work for them as individuals? If we do, does this affect self-care and treatment uptake through a supportive relationship which enhances treatment concordance? Once we have agreed treatment regimens, how do we measure the success or outcomes of them? This paper discusses these issues, and some of the tools that are available to assess adherence in a systematic way.

The experience of girls and young women with inherited bleeding disorders.

Haemophilia carriers and women with inherited bleeding disorders (IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers.

Management of surgical procedures in children with severe FV deficiency: experience of 13 surgeries.

Homozygous severe factor V (FV) deficiency has a prevalence of around one per million. Even in patients with FV levels of <0.01 IU mL(-1) there appears to be a variation in bleeding phenotype in that there is a subgroup of affected individuals who present in later childhood and have a relatively mild bleeding phenotype, but there are children who present as neonates with intracerebral bleeding events and who have a much more severe bleeding phenotype. The only available current FV replacement is in the form of fresh frozen plasma (FFP) or solvent detergent FFP. We present here our experience with surgical haemostatic cover for 13 surgeries in three children with severe FV deficiency.

Potential for development of haemophilia link nurse role within UK hospitals.

Link nurses are practising nurses with an expressed interest in a given specialty, with formal links to clinical nurse specialists and other specialist staff. The role involves attending meetings to discuss ideas and new developments, and relaying findings to other ward nurses to improve their practice. Such nurses are common in many specialties such as diabetes and tissue viability. In haemophilia, the role has the potential to enhance the care of haemophilia patients on general hospital wards. In April 2012, a focus group of five haemophilia nurses was convened to discuss their experiences of 'link nurse' programmes within district general hospitals and the potential value of developing the haemophilia link nurse role, and to consider the materials needed to support such role development. It was agreed to test whether other haemophilia nurses perceived such a need by means of a short five-item questionnaire devised by the group and made available to all members of the UK's Haemophilia Nurse's Association via Survey-Monkey. Final responses from 59 haemophilia nurses across the UK have been analysed. Most nurses agreed that there was value in the development of a haemophilia link nurse role within UK hospitals and thought their trusts would support it. While barriers and potential downsides were acknowledged, this was seen as a useful way of sharing information and knowledge with colleagues from different specialties and of raising awareness of bleeding disorders among the general nursing community. Haemophilia nurses should coordinate the development of a Haemophilia Link Nurse training and education pack.

Factors affecting the Haemophilia Joint Health Score in children with severe haemophilia.

Joint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high-titre inhibitors (HTI) and bleeding events influenced the Haemophilia Joint Health Score (HJHS) in children. Medical and physiotherapy notes of boys with severe haemophilia, aged 4-18 years, were reviewed to identify factors associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from 0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean 2.6). In the non-HTI group, the HJHS for boys on late prophylaxis was 2.68 times higher than those who started early and the HJHS was on average 10% higher for every additional recent bleed. In this group the odds of having a zero score fell by 30% for every year increase in age. Boys with a history of HTI had higher HJHS scores than the non-HTI group, and age, number of recent bleeds and tolerized status were positively associated with HJHS. The score rose on average by 28% for every year of age and by 76% for non-tolerized boys. This study provides further evidence supporting early prophylaxis use and the importance of immune tolerance therapy. The HJHS is a useful tool for identifying and tracking changes in joint health with respect to therapy or disease progression. With improvements in haemophilia treatment, the disproportionate number of zero scores will continue to make interpretation of the HJHS challenging.

The benefits of prophylaxis: views of adolescents with severe haemophilia.

It is well known and often reported that patients with long-term health conditions have problems adhering to treatment regimens. This is often reportedly worst in adolescents who struggle with the physical and psychological impact of adolescence as well as with the limitations that treatment regimens impose on their day-to-day activities. This article presents results from a larger study that aimed to discover what living with haemophilia in the 21st century was like for boys with severe haemophilia. The overall study was a multi-method, cross-sectional interview based study of 30 boys with severe haemophilia, treated with prophylaxis at a single site in the UK. Although not specifically asked in the interview schedule, opinions about treatment (prophylaxis) were given by 66% of the boys. These boys recognized that prophylaxis offered them protection from bleeding, the older and more sporty boys understood the need for tailored prophylaxis around 'risk' activities such as sport or events away from home. For some boys this meant low dose daily prophylaxis, and this further enhanced treatment adherence, as it became firmly embedded in their daily ritual of health care. This study shows that adolescent boys are in fact adherent with treatment, possibly at a schedule decided upon by them rather than one directed by the haemophilia centre. They are able to comprehend complex treatment decisions and make treatment plans that offer them maximum protection with minimal interference in their day-to-day activities.

Social networking for adolescents with severe haemophilia.

Access to modern treatments allows adolescents with haemophilia to manage their haemophilia at home, with improved treatment outcomes and quality of life, but has reduced peer support and the potential for experiential learning from older peers. Social networking, aided by modern communication technologies, may offer health benefits through peer support. We sought to assess whether or not disease-specific social networking could benefit adolescents with severe haemophilia. A total of 150 adolescents (aged 10-18) with severe haemophilia A or B from 11 UK treatment centres or those who had attended focus groups to explore the potential for a social network designed specifically for their use were surveyed. Teenage boys with severe haemophilia in the UK who responded to an online and paper questionnaire (n = 47; 31% response rate) rarely knew of or socialized with others with haemophilia outside their families. Two-thirds of respondents said they would like to meet others. For 70% of boys, parents were the major source of information about haemophilia, yet more than half said they often had trouble finding answers to their questions. These boys frequently used online social networks to chat with friends. Adolescents with severe haemophilia frequently have limited contact with others and many wish to have greater contact. They may benefit from peer support and experiential learning gained through online social networking. The SixVibe restricted access social network is to be launched in 2011. It includes features designed to promote and facilitate the development of peer-to peer disease management skills for adolescents with severe haemophilia.

The impact of sport on children with haemophilia.

Sport is nowadays perceived as beneficial for children with haemophilia, as good muscle strength supports joints and may reduce bleed frequency; by contrast psychological benefits are less known. This study introduces the impact of sport on health-related quality of life (HRQoL) and physical performance in children with haemophilia. A cross-sectional, multi-site, study of boys aged 6-17 years with haemophilia A or B of any severity, current or past inhibitor, which assessed physical performance, sporting activity and HRQoL using age appropriate questionnaires including KINDL, Haemo-QoL and HEP-Test-Q. Eighty-four haemophilic boys (23 mild, 19 moderate, 42 severe) with a mean age of 11.52 years (SD = 3.4) were enrolled from two haemophilia centres in the United Kingdom. 28.4% were overweight/obese according to their BMI/age and had a good orthopaedic status (M = 1.55, SD = 3.3). Boys watching < 1-2 h of TV/PC/day had fewer days lost (M = 3, SD = 3.2) than those with a more sedentary lifestyle (M = 9.40, SD = 7.1) (P < 0.032). 90.5% participated in regular sporting activity; 79.9% at least twice a week. HRQoL in children was generally good, with highest impairments in boys aged 8-12 years. Boys aged 8-16 years reported good physical performance (M = 80.0, SD = 16.0) with highest impairments in the dimensions 'endurance' and 'mobility'. Boys doing sport had a significant better physical performance and HRQoL than boys not doing sport. Sedentary life styles had a negative impact on the subjective physical performance and number of days lost of children. Encouraging haemophilic boys to participate in sport will have a direct impact on their overall HRQoL.

Why don't haemophilia nurses do research?

Clinical research should form a core component of the role of haemophilia nurse specialists. The UK Haemophilia Nurses Association sought to determine the barriers that prevent nurse specialists from engaging in research and to seek ways to promote clinical research by haemophilia nurses in the UK. Web-based survey with subsequent workshop discussion was conducted. Responses were received from 32 nurses (a 50% response rate), all of whom agreed that haemophilia nurses should be actively involved in nursing research although only 21 had actually participated in research specifically related to haemophilia practice. Of these, most research had been related to educational programmes or (less commonly) was limited to data collection as part of multidisciplinary studies. Involvement in research rarely resulted in publication. Some barriers to involvement in nursing research and subsequent publication were suggested by survey respondents. They also identified key practice areas that warranted nurse-based research including carriership and antenatal decision-making, along with the role and impact on care of the specialist haemophilia nurse, education and empowerment. To overcome the barriers to engaging in research and publishing, nurses require dedicated research time, mentorship and collaboration with more experienced haemophilia nurse researchers.

Early diagnosis of neonatal septicemia by hematologic scoring system, C-reactive protein and serum haptoglobin.

Neonatal septicemia is one of the major health problems throughout the world. Infections are frequent and important cause of morbidity and mortality in neonatal period. The objective of the present study was to find out the role of hematologic scoring system (HSS), C-reactive protein (CRP) and haptoglobin in the early diagnosis of neonatal septicemia. This is a descriptive consisted of 100 neonates admitted at neonatal ICU, BSMMU, who were clinically suspected sepsis. The hematological parameter, C-reactive protein and haptoglobin were measured in all cases. Blood culture was done as the gold standard for diagnosis of neonatal septicemia. There were 12 out of 100 neonates (12%) who had culture proven sepsis and they were predominantly preterm and very low birth weight. On evaluation of various hematological parameters total leukocyte count, total neutrophil count, immature to total neutrophil ratio (>0.2), immature to mature neutrophil ratio (>0.3), total immature count, platelet count were found to have optimal sensitivities and negative predictive values. Using these values hematologic scoring system (HSS) was formulated according to Rodwell et al. Score ≥4 was found sensitivity of 100%, specificity of 60%. C-reactive protein (CRP) had sensitivity of 75%, specificity of 74%. Haptoglobin was not found significant (p<0.05) with sepsis and sensitivity was very low. But Combination of score ≥4 and CRP showed sensitivity of 75%, specificity 85%, positive predictive value (PPV) 41% and negative positive value (NPV) 96%. HSS and CRP are useful test to differentiate the septicemic from non septicemic neonates and also provide a effective guideline to make decisions regarding judicious use of antibiotic therapy. But haptoglobin level was not found useful for screening of sepsis.