bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased breakthrough bleeding during prophylaxis with B‐domain deleted factor VIII – a robust meta‐analytic finding
Authors: Gruppo R. A. , Brown D. , Wilkes M. M. , Navickis R. J.
Published: September 2004

Summary.  Meta‐analyses of observational studies have become increasingly common to support evidence‐based clinical decisions. We analyzed currently available clinical studies of full‐length factor VIII (FL‐FVIII) vs. B‐domain deleted recombinant factor VIII (BDD‐rFVIII) using a random effects model to investigate possible differences in clinical efficacy in patients treated during prophylaxis. Some studies reported breakthrough bleeding incidence as mean annual total bleeds, whereas others reported median bleeds. In accord with the consensus recommendations by the Meta‐analysis of Observational Studies in Epidemiology (MOOSE) group, all available studies where included. For analysis, data were combined by converting median to mean annual total bleeds using a conversion factor of 2.6, based on clinical data previously compiled by the Universal Data Collection Program of the U.S. Centers for Disease Control and Prevention. To evaluate the sensitivity of our model upon the choice of conversion factor, we re‐estimated incidence rate ratios for breakthrough bleeding over a wide range of conversion factors from 1.4–2.6. Even at the lowest extreme conversion factor of 1.4, bleeding incidence was statistically higher in patients treated with BDD‐rFVIII compared with FL‐FVIII. We also examined the impact of reported patient age on our multivariate model. Exposure to BDD‐rFVIII remained an independent predictor of bleeding, regardless of patient age at start or mean age during prophylaxis. These analyses further support the robustness of our meta‐analysis and its conclusions.
Consensus recommendations for use of central venous access devices in haemophilia
Authors: Ewenstein B. M. , Valentino L. A. , Journeycake J. M. , Tarantino M. D. , Shapiro A. D. , Blanchette V. S. , Hoots W. K. , Buchanan G. R. , Manco‐Johnson M. J. , Rivard G.‐E. , Miller K. L. , Geraghty S. , Maahs J. A. , Stuart R. , Dunham T. , Navickis R. J.
Published: September 2004

Summary.  Venous access is essential for delivery of haemophilia factor concentrate. Wherever possible, peripheral veins remain the route of choice, and the use of central venous access devices (CVADs) should be limited to cases of clear need in patients with caregivers able to exercise diligence in CVAD care and should continue no longer than necessary. CVADs are of recognized value for repeated administration of coagulation factors in haemophilia, particularly for prophylaxis and immune tolerance therapy and in young children. Evidence to guide best practices has been fragmentary, and standardized methods for CVAD usage have yet to be established. We have developed management recommendations based upon available published evidence as well as extensive clinical experience. These recommendations address patient and CVAD selection; CVAD placement, care and removal; caregiver/patient guidance; and complications, including infection and thrombosis. In the absence of inhibitors, ports are recommended, primarily because of fewer associated infections than with external catheters. For patients with inhibitors, ports also appear to be associated with fewer infections. Infection is the most frequent complication, and recommendations to prevent and treat infections are supported by extensive clinical data and experience. Strict adherence to handwashing and aseptic technique are essential elements of catheter care. Evidence‐based data regarding the detection and treatment of CVAD‐related thrombotic complications are limited. Caregiver education is an integral part of CVAD use and the procedural practices of users should be regularly re‐assessed. These recommendations provide a basis for sound current CVAD practice and are expected to undergo further refinements as new evidence is compiled and clinical experience is gained.
Clinical efficacy, safety and pharmacokinetic properties of the factor VIII concentrate Haemoctin® SDH in previously treated patients with severe haemophilia A
Authors: Wolf D. M. , Rokicka‐Milewska R. , Lopaciuk S. , Skotnicki A. B. , Klukowska A. , Laguna P. , Windyga J. , Kotitschke R. , Struff W. G.
Published: September 2004

Summary.  Clinical efficacy, safety and pharmacokinetic properties of the high‐purity double‐virus inactivated plasma‐derived factor VIII concentrate Haemoctin® SDH (pdFVIII) were evaluated in three prospective open‐label uncontrolled studies in previously treated patients (PTPs) with severe haemophilia A. The pharmacokinetic properties assessed at baseline and after 3 months of treatment are in accurate accordance with published data and remain unchanged over time (study A, n = 12). Mean terminal elimination half‐life was 11.8 and 11.9 h, mean incremental recovery (IU dL−1/IU kg−1) was 2.3 and 2.0, respectively. Long‐term efficacy and safety, in particular the potential immunogenicity, were investigated in a total of 53 PTPs (studies A and B) treated prophylactically and on‐demand, as required. PdFVIII has shown to be effective in preventing and controlling bleeding episodes; 23.5% of patients were free of bleeding events. A total of 177 haemorrhages occurred with 74.0% resolving after a single infusion, 87.6% within two infusions. 98.3% of responses reported on haemorrhages were rated as ‘excellent’ or ‘good’. Moreover, ‘excellent’ haemostatic efficacy has been demonstrated in 10 surgical procedures including general and severe orthopaedic interventions (study C). No complication occurred in any surgery. Few adverse events were reported, one patient developed a high‐titre FVIII inhibitor without clinical relevance. In all three studies, over 6 million units were administered in nearly 4300 infusions, approximately 94% units or infusions were given for prophylaxis and only 6% for treatment on‐demand. In conclusion, pdFVIII has shown to be effective, safe and well tolerated in long‐term prophylaxis and treatment on‐demand as well as after minor and major surgical procedures.
Treatment patterns and cost‐of‐illness of severe haemophilia in patients with inhibitors in Germany
Authors: Auerswald G. , von Depka Prondzinski M. , Ehlken B. , Kreuz W. , Kurnik K. , Lenk H. , Scharrer I. , Schramm W. , Zimmermann R.
Published: September 2004

Summary.  To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost‐of‐illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first‐line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first‐line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15 kg) and adult patients (75 kg) from third party payers’ perspective. Cost for ITT ranges from €70 290 (2 months; LR) to €3 812 400 (24 months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from €287 500 (6 months; LR) to €17 253 000 (36 months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to €77 000 for a child and €354 000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.
Costs of on‐demand and prophylactic treatment for severe haemophilia in Norway and Sweden
Authors: Carlsson K. STEEN , Höjgård S. , Lindgren A. , Lethagen S. , Schulman S. , Glomstein A. , Tengborn L. , Berntorp E. , Lindgren B.
Published: September 2004

Summary. The expected annual cost (in the year 2000 prices) for a 30‐year‐old patient with average individual and treatment characteristics for on‐demand EUR 51 832 (95% CI: 44 324–59 341) and for prophylaxis EUR 146 118 (95% CI: 129 965–162 271), was obtained from panel‐data analysis of an 11‐year retrospective panel of 156 patients with severe haemophilia in Norway and Sweden. Costs included haemophilia‐related treatment costs within the health‐care sector (factor concentrate, doctors’ visits, diagnostic procedures, hospitalisation, invasive procedures, etc.) and cost for haemophilia‐related resource use in other sectors (lost production, use of special equipment, adaptation of workplace and domicile, etc). Although costs of lost production, reconstructive surgery and hospitalisation were higher for on‐demand, they did not balance out the higher costs of factor‐concentrate consumption in prophylaxis. The cut‐off risk of premature death, where on‐demand and prophylaxis would have been equally costly, was 3.7 percentage units higher for on‐demand than for prophylaxis. Such a great risk difference has not been reported elsewhere to our knowledge. Estimated cost‐elasticities indicated that annual costs of prophylaxis would increase by approximately the same proportion as a potential increase in the price of factor concentrate and decrease less than proportionately with a reduction in prescribed dose kg−1. For on‐demand, the annual costs would increase by approximately the same proportion as an increase in the prescribed dose kg−1.
The impact of unaware carriership on the clinical presentation of haemophilia
Authors: MacLean P. E. , Fijnvandraat K. , Beijlevelt M. , Peters M.
Published: September 2004

Summary.  This study was conducted to evaluate the effect of an unaware carriership on the delay in diagnosis of haemophilia and the resulting effect of this delay on morbidity. Information on 73 haemophilia patients (<18 years) and their mothers was gathered from data of patients’ medical records and completed by interviews with the parent(s). Although a positive family history was present in 52 gravidae, 16 of them (31%) were not aware of their carrier status at moment of delivery. Fifteen of these 16 unaware carriers, were carriers of a non‐severe form of haemophilia. In mothers who were unaware of carriership for haemophilia instrumental delivery occurred more frequently than in mothers who knew they were carriers. This is disquieting since instrumental delivery poses a significant risk (relative risk: 17.8, 95% CI: 4.0–78.4) for intra‐ or extracranial bleedings in newborn haemophiliacs in comparison to spontaneous deliveries or caesarean sections. In 83% of the patients with a positive family history, diagnosis was established before the first bleeding episode. Patients diagnosed by bleedings presented more often with iatrogenic bleedings (38%) then patients who were diagnosed because of a positive family history (9%) (P < 0.05). In comparison to previous studies, more patients had a positive family history and in more haemophiliacs with a positive family history diagnosis was established before the first bleeding episode. Although this reflects the yield of improved diagnostic methods, further reduction of iatrogenic bleeding is possible by intensifying counselling of mild haemophilia carriers.
Relationships between factor VIII:Ag and factor VIII in recombinant and plasma‐derived factor VIII concentrates
Authors: Lin Y. , Yang X. , Chevrier M.‐C. , Craven S. , Barrowcliffe T. W. , Lemieux R. , Ofosu F. A.
Published: September 2004

Summary.  A variety of plasma‐derived (pd) and recombinant (r) factor VIII (FVIII) concentrates are used to prevent and treat bleeding in severe hemophilia A patients. A significant side effect of FVIII replacement is the development of FVIII neutralizing antibodies (inhibitors) in up to 30% of patients receiving FVIII concentrates. The FVIII protein content (FVIII:Ag) per unit of FVIII:C in FVIII concentrates, and how effectively the FVIII:Ag in FVIII concentrates binds to von Willebrand factor (VWF) may provide information relevant for the survival of FVIII:C in vivo and for estimating the risk for inhibitor development. The FVIII:Ag content of nine r‐FVIII and nine pd‐FVIII concentrates were quantified in this study using two enzyme‐linked immunosorbent assay (ELISA) platforms. The two ELISA platforms were based on the use of a monoclonal anti‐(FVIII light chain)‐IgG and polyclonal anti‐FVIII antibodies as capture antibodies and both ELISAs were equally able to detect ≥0.005 IU of FVIII:Ag. Measured in international units, the r‐FVIII concentrates contained significantly higher FVIII:Ag per unit of FVIII:C than the pd‐FVIII concentrates. The VWF‐binding profiles of the r‐FVIII and pd‐FVIII concentrates were also determined by gel filtration chromatography. Unlike the plasma‐derived products, the r‐FVIII concentrates invariably contained a fraction of FVIII:Ag molecules (∼20%) which was unable to associate with VWF. Given that VWF regulates both factor VIII proteolysis and survival of FVIII:Ag in vivo, the fraction of FVIII:Ag unable to bind to VWF may have a reduced survival and be more susceptible to proteolytic degradation in vivo. The extent to which the fractions of FVIII:Ag in concentrates able and unable to bind to VWF contribute to inhibitor development in severe FVIII‐deficient patients is unknown.
Asking fathers: a study of psychosocial adaptation
Authors: Herrick E. K. , Nussbaum R. , Holtzman N. A. , Wissow L.
Published: September 2004

Summary. Although few contemporary studies specifically address paternal adaptation, the theme of paternal estrangement from medical care and from family relationships is pervasive in the psychosocial literature on haemophilia. This estrangement has been shown to have a negative effect on fathers’ psychological well‐being, marital relationships and the adaptive outcome of their sons who have haemophilia. The goals of this study were to provide contemporary data on the psychosocial adaptation of fathers of boys with haemophilia and to examine specific variables that might influence their adjustment. Eighty‐three eligible fathers returned a survey instrument that collected demographic and medical information, as well as scores on self‐measures of adaptation in marital and parenting roles. Statistically significant direct correlations (P < 0.01) were found between fathers’ scores on the Marital Adjustment Test and the Parenting Sense of Competence subscales (parenting efficacy and satisfaction). Variables specific to rearing a son with haemophilia that negatively affected fathers’ marital adjustment scores included: feeling left out of medical decision making by their wives or partners, worry about their sons’ having limited activity, and the presence of a secondary diagnosis in the affected child. Scores on the parenting efficacy subscale of the PSOC were statistically significantly reduced (i.e. fathers felt less effective in the parenting role) in men who ‘rarely’ or ‘never’ infused their sons (42/80, 53%). Variables that negatively affected scores on the parenting satisfaction subscale included frustrating interactions with medical staff and concern about their sons’ potential to contract an infection or secondary diagnosis. This paper presents a model to examine the interrelationships among the data and discusses the clinical implications.
HLA class II genotype and factor VIII inhibitors in mild haemophilia A patients with an Arg593 to Cys mutation
Authors: Bril W. S. , MacLean P. E. , Kaijen P. H. P. , van den Brink E. N. , Lardy N. M. , Fijnvandraat K. , Peters M. , Voorberg J.
Published: September 2004

Summary.  We evaluated inhibitor formation in a group of patients with mild haemophilia A caused by an Arg593 to Cys mutation. A remarkably high cumulative inhibitor incidence of 14% over 22 years was observed. Three of 49 patients developed transient, low‐titre inhibitors, which remained below 2.0 BU mL−1. Four patients with an Arg593 to Cys mutation developed high‐titre inhibitors (>5.0 BU mL−1). Three of these patients have been described previously. In this study, we characterized inhibitory antibodies in a fourth patient with high‐titre inhibitors. Epitope mapping studies revealed that antibodies were predominantly directed to the A2 domain of factor VIII. We addressed the role of human leucocyte antigen (HLA) class II alleles in inhibitor development in patients with an Arg593 to Cys mutation by HLA genotyping. In the group of inhibitor patients raised frequencies of HLA‐DRB1*01 and HLA‐DQB1*05 were observed that did not reached statistical significance. Our data suggest that inhibitor development in mild haemophilia A patients with an Arg593 to Cys mutation is not linked to HLA class II profile.
Continuous infusion of B‐domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience
Authors: Stieltjes N. , Altisent C. , Auerswald G. , Négrier C. , Pouzol P. , Reynaud J. , Roussel‐Robert V. , Savidge G. F. , Villar A. , Schulman S.
Published: September 2004

Summary. This retrospective, open‐label, non‐comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto®), B‐domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as ‘excellent’ or ‘good’ in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non‐haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non‐serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild‐to‐moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well‐tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well‐tolerated regimen for patients with haemophilia A undergoing surgery.
Bacterial enteritis and the development of the larval digestive tract in olive flounder, Paralichthys olivaceus (Temminck & Schlegel)
Authors: Kim D‐H , Han H‐J , Kim S‐M , Lee D‐C , Park S‐I
Published: September 2004

Three bacterial isolates obtained from diseased olive flounder larvae, Paralichthys olivaceus, were identified as Vibrio ichthyoenteri based on the results of phenotypic characterization and 16S rRNA gene sequencing studies. Bacterial enteritis was reproduced in 16 and 22 days post‐hatch (dph) larvae by administering brine shrimp nauplii, Artemia salina, dosed with the environmental isolates and reference strains of V. ichthyoenteri. To investigate the effect of the disease on development of the stomach, a pepsin activity assay and reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of the expression of the pepsinogen gene were performed. Expression of olive flounder pepsinogen was detected from 30‐dph larvae and the increased level of pepsin activity coincided with reduced susceptibility to the disease. Growth rates of V. ichthyoenteri, V. anguillarum and Edwardsiella tarda were tested in artificial stomach conditions using HCl and porcine pepsin. All the strains of V. ichthyoenteri were inhibited by low pH conditions which corresponded with an increase in pepsin levels. This suggests that differentiation of the stomach in olive flounder larvae and juveniles, an essential physiological development, also provides the host with a non‐immunological defence mechanism.
Nutritional changes among premenopausal women undertaking a soya based dietary intervention study in Hawaii
Authors: Acharya S. , Maskarinec G. , Williams A. E. , Oshiro C. , Hebshi S. , Murphy S. P.
Published: September 2004

Background  We conducted a 2‐year nutritional intervention among premenopausal women. The goal was to incorporate two daily servings of soya into the regular diet. This report describes the dietary modifications and assesses their nutritional adequacy with regard to major nutrients.

Methods  In this analysis of 100 intervention and 106 control subjects, women completed a validated food‐frequency questionnaire at baseline; throughout the study, they participated in at least three unannounced 24‐h recalls.

Results  At randomization, both groups were similar in age and body weight, reported low soya intake, and did not differ by intake of major nutrients and foods. According to the 24‐h recalls, women in the intervention group consumed nearly two servings of soya per day, while the control women remained at 0.2 servings. In comparison with the control group, the intervention group consumed fewer dairy products, primarily milk, but also less meat, nuts and seeds. As a result of the dietary modification, the intervention women consumed less‐saturated fat and cholesterol and more protein, dietary fibre, calcium and vitamins than the control group.

Conclusion  These results suggest that women in the intervention group improved the overall quality of their diet by adding two servings of soya per day.
The health benefits of omega‐3 polyunsaturated fatty acids: a review of the evidence
Authors: Ruxton C. H. S. , Reed S. C. , Simpson M. J. A. , Millington K. J.
Published: September 2004

The UK dietary guidelines for cardiovascular disease acknowledge the importance of long‐chain omega‐3 polyunsaturated fatty acids (PUFA) – a component of fish oils – in reducing heart disease risk. At the time, it was recommended that the average n‐3 PUFA intake should be increased from 0.1 to 0.2  g day−1. However, since the publication of these guidelines, a plethora of evidence relating to the beneficial effects of n‐3 PUFAs, in areas other than heart disease, has emerged. The majority of intervention studies, which found associations between various conditions and the intake of fish oils or their derivatives, used n‐3 intakes well above the 0.2 g day−1 recommended by Committee on Medical Aspects of Food Policy (COMA). Furthermore, in 2004, the Food Standards Agency changed its advice on oil‐rich fish creating a discrepancy between the levels of n‐3 PUFA implied by the new advice and the 1994 COMA guideline. This review will examine published evidence from observational and intervention studies relating to the health effects of n‐3 PUFAs, and discuss whether the current UK recommendation for long‐chain n‐3 PUFA needs to be revisited.
Eyewitness testimony and perceived credibility of youth with mild intellectual disability
Authors: Peled M. , Iarocci G. , Connolly D. A.
Published: September 2004

Background  Individuals with intellectual disability (ID) are more vulnerable to abuse compared to individuals without disabilities yet have limited access to the legal system. This study examined perceived credibility of youth with mild intellectual disability (MID) who provide courtroom testimony.

Method  Participants, 187 undergraduates, were asked general questions about credibility. They also read eyewitness testimony and answered questions about a particular witness's credibility. Half the participants were informed that the youth has MID [chronological age (CA) 15 years, mental age (MA) 10 years] and the others were informed that the youth is a typically developing 10‐year‐old.

Results  When participants were asked general questions about credibility they rated 15‐year‐olds with MID (MA 10 years) as less credible than typically developing 15‐year‐olds and as less credible than typically developing 10‐year‐olds. However, when participants read eyewitness testimony and answered questions about a particular witness's credibility, no statistically significant differences were found between participants who were informed that the witness was a 15‐year‐old with MID (MA 10 years) and those who were informed that the witness was a typically developing 10‐year‐old.

Conclusions  The present study provided a preliminary investigation of perceived credibility of witnesses with MID and suggests directions for future research in this area.
Effects ofHelicobacter pylorieradication among adults with intellectual disability
Authors: Wallace R. A. , Schluter P. J. , Webb P. M.
Published: September 2004

Background Compared to the general population,Helicobacter pyloriinfection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success of a standardH. pylorieradication protocol; (2) frequency of side‐effects; and (3) impact of eradication on level of functional ability and maladaptive behaviour.

Method A cohort of adults with ID underwent assessment of their levels of function and maladaptive behaviour, medical history, physical examination, andH. pyloritesting using serology and faecal antigen tests. Some received standardH. pylorieradication therapy. Twelve months later, participants underwent repeat assessment, were grouped by change inH. pyloristatus and compared.

Results Of 168 participants, 117 (70%) were currently infected withH. pyloriat baseline, and 96 (82%) of the 117 were given standardH. pylorieradication therapy. The overall eradication rate was 61% but 31% reported side‐effects. Institutional status of the participants, their level of behaviour or function, and number of comorbid medical conditions were not associated with failure of eradication. There were no statistically significant differences in level of behaviour or function, ferritin, or weight between the groups in whomH. pyloriwas eradicated or stayed positive.

Conclusion Adults with ID have lowerH. pylorieradication and higher side‐effect rates than the general population. Levels of maladaptive behaviour and disability did not improve with eradication and thus greater levels of maladaptive behaviour or disability appear to be risk factors for, rather than consequences of,H. pyloriinfection.
Two cases of generalized seizures and the Velocardiofacial syndrome – a clinically significant association?
Authors: El Tahir M. O. , Kerr M. , Jones R. G.
Published: September 2004

Background  Velocardiofacial syndrome (VCFS) is caused by a micro deletion of chromosome 22q11 and associated with multiple system abnormalities. There is an increasing recognition of associations with psychiatric disorders. Neurological and brain abnormalities have been reported but to date no association with generalized epilepsy has been reported in literature.

Methods  We report two cases of adults with VCFS and primary generalized epilepsy. The details on their background, psychiatric history and history of epilepsy including results of investigations will be discussed.

Results  Case 1 is an adult male with mild learning disability (LD), VCFS, paranoid schizophrenia and primary generalized epilepsy. Case 2 is an adult female with mild LD, VCFS, schizoaffective disorder and primary generalized epilepsy. The diagnosis of epilepsy in both cases was based on clinical and EEG findings of primary generalized abnormalities.

Conclusion  As there is an evidence of association between VCFS and psychiatric disorders, this raises the possibility of an association with generalized epilepsy.
Utilization of inpatient care and its determinants among persons with intellectual disabilities in day care centres in Taiwan
Authors: Lin J. D. , Wu J. L. , Lee P. N.
Published: September 2004

Background  In Taiwan, current understanding is limited concerning the manner in which health services are utilized by persons with intellectual disabilities (ID). The objective of this study is to describe the patterns of inpatient care sought by persons with ID, and factors affecting inpatient care utilization.

Method  The primary method used in this study was a cross‐sectional survey of 1390 persons with ID in day care centres. Data were obtained from responses to a questionnaire, copies of which were mailed to 30 day care centres catering for persons with ID. The questionnaire assessed demographic and health characteristics, disability status, and inpatient care utilization for the 12 months leading up to the survey. Multivariate logistic regression analysis identified factors independently associated with inpatient care.

Results  Findings indicated that the average age of the people with ID in the centres was 13.7 years. Fifty per cent of people were afflicted with multiple handicaps, with an average of 26 outpatient visits made per person during the 12 months, and 16% of persons having been hospitalized within the previous year. The average hospital stay was 6 days. Inpatient care was more likely to be used by those individuals with an ID who were younger, had multiple handicaps, required rehabilitation, and had other disabilities and existing illnesses.

Conclusions  The study concluded that the parameters describing age of persons with ID, as having an existing illness, and requiring rehabilitative care were statistically significant in the logistic regression model of the inpatient care.
Mild intellectual disability in children in Lahore, Pakistan: Aetiology and risk factors
Authors: Yaqoob M. , Bashir A. , Zaman S. , Ferngren H. , Von Dobeln U. , Gustavson K.‐H.
Published: September 2004

Background  One of the main objectives of studying intellectual disability (ID) in children is to explore its causes. A specific aetiological diagnosis is important in determining the prognosis, nature and extent of services needed to support affected children.

Methods  Aetiology and risk factors in mild ID were studied in a cohort of longitudinally followed children (6–10 years of age, n = 40) in four population groups in and around Lahore, Pakistan.

Results  The overall prevalence of mild ID was 6.2%. In 22% of the cases the onset of mild ID was prenatal with small for gestational age and multifactorial inheritance as the main underlying factors. During the postnatal period (28% of the cases), social deprivation and malnutrition were the major causes of ID. In a substantial proportion of the cases (50%), the cause of ID could not be traced.

Conclusion  The present study indicates a clear relationship of mild ID with prenatal and postnatal malnutrition and social deprivation. Two independent variables, maternal illiteracy and small head circumference at birth, showed a clear association with the development of mild mental disability among children in the study population.
An analogue assessment of repetitive hand behaviours in girls and young women with Rett syndrome
Authors: Wales L. , Charman T. , Mount R. H.
Published: September 2004

Background Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. In addition to neurodevelopmental regression and loss of hand skills, apraxia, deceleration of head growth, and increasing spasticity and scoliosis, a number of behavioural features are also seen, including stereotypic hand movements, hyperventilation and breath holding. The aim of the study was to investigate the extent to which analogue environmental conditions affected the frequency of repetitive hand behaviour in eight girls and young women with Rett syndrome.

Method The frequency of repetitive hand movements was observed every 10 s for four 4‐min sessions under the following conditions: Continuous Adult Attention, Adult Demands, Stimulation and No Stimulation.

Results The frequency of repetitive hand movements was high – they occurred in above 60% of all intervals in all conditions for all participants and at nearly 100% for some participants in some conditions. For one participant the frequency of repetitive hand movements was somewhatreducedin the Stimulation condition; for another it was relativelyincreasedin the No Stimulation condition.

Conclusions Overall, environmental manipulations had relatively limited effects on repetitive hand behaviours. Repetitive hand behaviour in Rett syndrome may be maintained by automatic reinforcement or neurochemical processes and may not be primarily influenced by contingent reinforcement.
Late diagnosis in severe and mild intellectual disability in adulthood
Authors: Verri A. P. , Maraschio P. , Uggetti C. , Pucci E. , Ronchi G. , Nespoli L. , Destefani V. , Ramponi A. , Federico A.
Published: September 2004

Background  The diagnosis of intellectual disability (ID) is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the patient. Our study intended to: (1) classify the aetiology of mild and severe ID in an adult population of 140 Italian subjects; (2) evaluate the frequency of associated medical conditions; (3) evaluate the age of diagnosis in both groups; and (4) underline the importance of aetiological diagnosis for adult ID patients also.

Methods  The study involved 140 consecutive adult Italian ID inpatients and outpatients neurologically investigated at the Neurological Institute C. Mondino of Pavia Service for Mental Retardation. A total of 80 patients had mild ID (MID group) (39 females, 41 males), mean age 34 years (range 19–61 years), mean IQ = 64 (range 51–75), and 60 had severe ID (SID group) (32 females, 28 males), mean age 30 years (range 19–69 years). They underwent a complete diagnostic work‐up that comprised prenatal, perinatal and postnatal history, physical examinations, laboratory investigations, genetic survey and neuroradiological investigations to determine the aetiology of ID and to evaluate the presence of associated medical conditions.

Results  ID aetiology was classified as prenatal in 34% of the MID and 28% of the SID group. Perinatal and postnatal events were found in 6% of the MID and in 5% of the SID group. Associated medical conditions were found in 97 patients (47% MID and 26% SID). A genetic diagnosis was possible in 6% of patients above 20 years of age and in 5% of patients above 40 years. A diagnosis of cerebral dysgenesis was possible in 5% of patients above 20 years and 4% of patients above 40 years.

Conclusions  A long interval between the diagnosis of ID and the aetiological definition can be observed in a significant percentage (24%) of our population, leading to unfortunate consequences of late diagnosis: late onset of a specific therapeutic program, genetic counselling that is frequently no more useful, and ineffective prenatal diagnosis, leading to the birth of other affected subjects (for familiar ID).
A prospective study of the use of cryosurgery for the treatment of actinic keratoses
Authors: Thai Keng‐Ee , Fergin Peter , Freeman Michael , Vinciullo Carl , Francis David , Spelman Lynda , Murrell Dedee , Anderson Chris , Weightman Warren , Reid Catherine , Watson Alan , Foley Peter
Published: September 2004

Background  Actinic keratoses are the most common actinic lesions on Caucasian skin. Cryosurgery with liquid nitrogen is commonly used to treat actinic keratoses, but there have been few studies examining the true rate of cure in everyday dermatologic practice.

Aim  To determine prospectively the true efficacy of cryosurgery as a treatment for actinic keratoses in everyday dermatologic practice.

Methods  A prospective, multicentered study (a subsidiary study of a photodynamic therapy trial) was performed. Patients with untreated actinic keratoses greater than 5 mm in diameter on the face and scalp were recruited. Eligible lesions received a single freeze–thaw cycle with liquid nitrogen given via a spray device and were reviewed 3 months thereafter. Each center used their preferred freeze time. The only treatment criterion was complete freezing of actinic keratoses and a 1‐mm rim of normal skin. Treated lesions were assessed as complete response or noncomplete response. The influence of the duration of freeze, cosmetic outcomes, and adverse events were examined.

Results  Ninety adult patients from the community with 421 eligible actinic keratoses were recruited. The overall individual complete response rate was 67.2%[SEM = ±3.5%; 95% confidence interval (CI) = 60.4–74.1%]. Complete response was 39% for freeze times of less than 5 s, 69% for freeze times greater than 5 s, and 83% for freeze times greater than 20 s. Cosmetic outcomes were good to excellent in 94% of complete response lesions. The main adverse events were pain, stinging, and burning during treatment, and hypopigmentation after healing.

Conclusions  Cryosurgery is an effective treatment for actinic keratoses. The true complete response rate is significantly lower than that previously reported. The freeze duration influences successful treatment. Adverse events are mild and well tolerated.
Pemphigus vulgaris with involvement of the cervix treated using thalidomide therapy
Authors: Cunha Paulo Rowilson , De Oliveira Josenildo Rodrigues , Salles Maria José , Jamora Jasmin , Bystryn Jean‐Claude
Published: September 2004

A 55‐year‐old White woman was first seen in July 1995 with ulceration of the oral mucosa, including the gingiva, labial mucosa, gums, palate and tongue, as well as erosions and blisters on the trunk. A biopsy showed a suprabasal blister with acantholysis. Direct immunofluorescence was positive for intercellular deposits of IgG and C3, and indirect immunofluorescence was positive for intercellular antibodies at a titer of 160. The patient was diagnosed as having pemphigus vulgaris and treated with prednisone 1–1.5 mg/kg/day from 1995 until 1998, but no response was observed (the disease continued to be active with the formation of new lesions). The patient developed a number of steroid‐induced complications including diabetes, osteoporosis, Cushing syndrome, hypertension and high‐output cardiac failure, and required repeated hospitalization. In August 1998 she was started on azathioprine 100–150 mg/day and continued on prednisone 1 mg/kg/day. One year later, in August 1999, the disease was still active with new lesion formation and persistent oral erosions and dysphagia, despite persistent therapy with azathioprine 150 mg/day and prednisone 1 mg/kg/day.

Because of the disease severity and the lack of a response to treatment, in October 1999 the patient was started on thalidomide therapy 100 mg/day (1.7 mg/kg/day) and continued the prednisone treatment at 1 mg/kg/day together with azathioprine 150 mg/day (2.7 mg/kg/day). There was a good response, with clearing of all oral lesions in 20 days. The prednisone dose was gradually reduced and was discontinued in May 2000; azathioprine was gradually reduced to 50 mg 3 times/week (0.35 mg/kg/day). Thalidomide was continued at a dose of 100 mg/day. The patient was in total clinical remission, being free of both old and new lesions, for the next 14 months, when the thalidomide treatment was discontinued as a result of side‐effects, including weakness in the legs and paresthesis of the fingers.

After the discontinuance of treatment with thalidomide, severe lesions returned. Thalidomide was reintroduced, at 100 mg/day. After 2 months the patient entered total clinical remission and on the last occasion on which she was seen, in May 2003, was found to have remained clear of lesions. The patient continues to take thalidomide at 100 mg/day.
Itraconazole in the treatment of New World mucocutaneous leishmaniasis
Authors: Calvopina Manuel , Guevara Angel G. , Armijos Rodrigo X. , Hashiguchi Yoshihisa , Davidson Robert N. , Cooper Philip J.
Published: September 2004

Background  A well‐tolerated oral drug is required for the treatment of mucocutaneous leishmaniasis (MCL). Current parenteral treatment regimens with pentavalent antimonials are associated with marked toxicity and significant rates of relapse.

Aim  To evaluate the efficacy and tolerability of high‐dose itraconazole for the treatment of MCL.

Methods  An uncontrolled treatment study was performed in 13 Ecuadorian patients with MCL. Each patient received a daily dosage of 400 mg of itraconazole for a minimum of 3 months.

Results  All 13 subjects responded to itraconazole during the first month of treatment, but by 12 months after treatment the complete resolution of MCL lesions was observed in only three (23%) subjects. No adverse effects of treatment were reported. Response to treatment was associated with a short evolution of the disease and mild to moderate disease severity.

Conclusion  Prolonged and high‐dose treatment regimens with itraconazole are not effective for the treatment of the majority of patients with MCL.
The association of hepatitis A and Helicobacter pylori with sensitization to common allergens, asthma and hay fever in a population of young British adults
Authors: Jarvis D. , Luczynska C. , Chinn S. , Burney P.
Published: September 2004

Background:  A negative association of oro‐faecally spread infection with serological markers of sensitization and allergic disease has been reported.

Method:  Previous infection with hepatitis A and Helicobacter pylori was assessed in a community‐based sample of young British adults and associations with serum‐specific IgE to environmental allergens, asthma‐like symptoms and hay fever were examined.

Results:  There was no association of previous infection with hepatitis A or H. pylori with wheeze or hay fever. There was no evidence of an association of infection with either agent and sensitization except for the isolated finding of a lower prevalence of sensitization to grass in those with IgG antibodies to H. pylori (OR 0.65, 95% CI 0.43–0.99). This association did not explain the negative association of family size with sensitization to grass.

Conclusion:  In this population, there was no evidence that infection with hepatitis A or H. pylori was associated with lower levels of IgE sensitization, asthma or hay fever except for an isolated finding of a negative association of H. pylori infection with sensitization to grass.
Atopic disorders among Estonian schoolchildren in relation to tuberculin reactivity and the age at BCG vaccination
Authors: Annus T. , Montgomery S. M. , Riikjärv M.‐A. , Björkstén B.
Published: September 2004

Background:  Published data about a relationship of atopic diseases to Bacillus Calmette‐Guérin (BCG) vaccination and tuberculin responses are inconsistent. Our aim was to determine this association in a country with a low prevalence of allergies.

Methods:  A random sample of 10–11‐year‐old schoolchildren in Tallinn was studied by a parental questionnaire (n = 979) and skin‐prick tests (n = 643), according to the International Study of Asthma and Allergies in Childhood. Data about BCG vaccinations and tuberculin tests were obtained from school records (n = 723).

Results:  The prevalence of allergic symptoms and atopy was similar in children vaccinated during the first month of life and later. Positive tuberculin responses (≥5 mm) were inversely related to symptoms of asthma [odds ratio (OR) 0.10 (95% confidence interval 0.00–0.68) for exercise‐induced wheezing; OR 0.37 (0.12–0.99) for night cough], and eczema [OR 0.53 (0.28–0.98)] but not to atopy. However, among BCG‐revaccinated children, atopy tended to be more common in tuberculin responders, and the atopic children were significantly more likely to have a positive tuberculin response after the revaccination than would be predicted by their first test.

Conclusions:  We found no protective effect of early BCG vaccination against atopy in school age, although tuberculin responses and allergic symptoms were inversely related.
Lipoxins in asthma: potential therapeutic mediators on bronchial inflammation?
Authors: Bonnans C. , Chanez P. , Chavis C.
Published: September 2004

Arachidonic acid metabolism represents an important source of mediators with ambivalent actions. Among these, lipoxins (LXs) are the first agents identified and recognized as anti‐inflammatory endogenous lipid mediators, which are involved in the resolution of inflammation and are present in the airways of asthmatic patients. Lipoxins result mainly from the interaction between 5 and 15‐lipoxygenases (LO) and their levels are modulated by the degree of bronchial inflammation as well as by the long‐term glucocorticoid treatments. In the airways, LX synthesis is higher in mild asthmatics than in severe asthmatics, whereas in vitro chemokine release inhibition by LXs is more effective in cells from severe asthmatics than from mild asthmatics. LipoxinA4 effects on interleukin (IL)‐8 released by blood mononuclear cells and on calcium influx in epithelial cells are mediated by the specific receptor ALX. Lipoxin generation by lung epithelial cells depends mainly on 15‐LO activity. Mild asthmatics present higher 15‐LOb expression at the epithelium level than severe patients, whereas the LX deficit in severe asthma is associated with an up‐regulation of the 15‐LOa expressions. Therefore, bronchial epithelial cells become a target for therapeutic intervention and LXs represent a potential therapeutic solution for bronchial inflammation resolution in asthma.
The basophil activation test in wasp venom allergy: sensitivity, specificity and monitoring specific immunotherapy
Authors: Erdmann S. M. , Sachs B. , Kwiecien R. , Moll‐Slodowy S. , Sauer I. , Merk H. F.
Published: September 2004

Background:  As in vitro diagnosis of wasp venom sensitization by specific serum IgE has a sensitivity of only 60–80%, additional in vitro tests are desirable. Basophil activation is associated with the expression of CD63 and its measurement has been proposed as a novel in vitro test for immediate‐type allergy. Furthermore, to date, no in vitro test exists to monitor successful specific immunotherapy (SIT) with wasp venom. Therefore, the potentially harmful sting challenge is still recommended.

Objective:  We compared the CD63‐based basophil activation test (BAT) in the diagnosis of wasp venom allergy with skin tests and measurement of specific IgE. Furthermore, we investigated whether BAT can predict the outcome of the sting challenge in patients on SIT.

Methods:  Fifty patients with a systemic reaction caused by a wasp sting and 20 controls were studied. Intracutaneous tests were performed with wasp and bee venom in the suspected allergics. Specific IgE was determined by the CAP‐FEIA method and basophil activation by flow cytometry upon double staining with anti‐IgE/anti‐CD63 mAb. Twenty‐five patients were sting challenged 6 months after starting SIT and the BAT was repeated before challenge.

Results:  Sensitivity of the intracutaneous tests, specific IgE and BAT was 100, 76, and 92%, respectively. Specificity of specific IgE and the BAT was 85 and 80%, respectively. The cut‐off for a positive BAT was 15% CD63+ basophils. There was a positive correlation between IgE reactivity to wasp venom and the number of CD63+ basophils (r = 0.65). Although no patient had a systemic reaction upon sting challenge, in most subjects basophil activation did not decrease when compared with the BAT before SIT.

Conclusions:  Quantitation of basophil activation by CD63 expression is a valuable new in vitro method for diagnosis of allergy to hymenopteran venoms. The CD63‐based BAT is a helpful tool for the complementation of routine diagnostic tests such as specific IgE as it increases sensitivity of in vitro detection of sensitization. However, this in vitro method does not offer an alternative to the sting challenge in monitoring successful SIT.