Bone disease in patients with haemophilia A and B – where are we now?

It is evident that haemophilia A and B are associated with decreased bone mass in both adults and children. Decreased physical activity and vitamin D deficiency are some of the major factors leading to bone loss. Hepatitis C virus (HCV) infection may also contribute to low bone mineral density (BMD). However, definite conclusions regarding the exact prevalence and pathogenesis of osteoporosis cannot be conducted yet, due to the small sample size and significant heterogeneity among studies. Discordant findings with regard to the skeletal site of low BMD have also been reported. Furthermore, data on fracture risk are sparse. The use of the Fracture Risk Assessment Tool (FRAX) for assessing fracture risk, regular BMD assessment at the age of 25 and thereafter, careful evaluation of risk factors associated with bone loss and optimal calcium and vitamin D intake are recommended. Long‐term prophylactic factor replacement therapy, resistance exercise and bisphosphonates, in severe cases of increased fracture risk, can prevent bone loss.     

How to manage IBD in patients with infections or malignancies?

Infections and malignancies are a major issue for clinicians in the management of patients with IBD because of concerns about the safety of drugs currently used in treatment, including immunosuppressive agents, steroids and tumor necrosis factor (TNF) antagonists. Infections are strongly associated with IBD both in their etiopathogenesis and in their clinical course. A number of viral infections, tuberculosis and other therapy-related infections create challenges for the successful management of intestinal disease with immunosuppressive agents or TNF antagonists. Recently published guidelines offer a strong support to deal with these issues. Major concern about IBD patients with malignancies is related to the consequences of chemotherapy on the intestinal disease, the risk of maintaining immunosuppressant or anti-TNF therapy after the diagnosis of malignancy and the management of a clinical relapse of IBD in patients with a recent diagnosis of malignancy. Further research is required to optimize strategies for IBD patients with malignancies. At the moment, all therapeutic choice is made on an individual basis, with an integrative multidisciplinary approach.     

Is on‐demand treatment effective in patients with severe haemophilia?

Summary. On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.     

Infliximab in Takayasu arteritis: a safe alternative?

Objective To test the efficacy of Infliximab, a chimeric monoclonal antibody against TNF-α, in the treatment of Takayasu arteritis. Materials and methods We used infliximab at an initial dose of 3 mg/kg i.v. at weeks 0, 2, 6, and 8 thereafter in combination with methotrexate or azathioprine, to treat four patients with Takayasu arteritis. Results Three out of four patients responded to infliximab treatment, while two of them retained the response during a two-year follow up. A higher dose regimen (5 mg/kg), however, was eventually warranted for two of the responders. No major side effects were noted. Conclusions Infliximab might be an effective and safe alternative for patients with Takayasu arteritis.     

What patient,joint and isotope characteristics influence the response to radiosynovectomy in patients with haemophilia?

Summary. The literature describes radiosynovectomy (RS) as a good non‐surgical option for reducing synovial membrane size and thus the number of haemarthrosis episodes. However, there are still many aspects concerning the beneficial effects of RS that have not been quantified. A total of 156 radiosynovectomies (RS) were performed in 104 joints corresponding to 78 haemophiliacs (yttrium‐90, rhenium‐186). The mean patient age was 18 years. In another study involving the same group of patients, the parameters that improved most after RS were pain and haemarthrosis, followed by the World Federation of Hemophilia clinical score, muscle strength and range of movement (ROM). Following RS, improvement was seen to be independent of patient age, haemophilia type and grade, previous haematological treatment, the presence or absence of circulating inhibitor, synovial membrane size, the type of joint (elbow, knee and ankle), previous physical activity or lack of activity, the prior presence or absence of radiographic signs of joint degeneration (arthropathy) or the isotope used. RS is effective in treating haemophilic synovitis and may require 1–3 injections (RS‐1, RS‐2 and RS‐3) spaced 6 months apart. Following RS‐1, the knee had a 3.4‐ and 3.2‐fold greater risk of not improving in terms of pain, compared with the elbow and ankle, respectively. Regarding ROM, lesser improvement was recorded after RS‐1 in cases of severe haemophilia and the ankle. In other words, severe haemophilia implies a 2.1‐fold greater risk of no improvement in ROM compared with mild and moderate haemophilia. In addition, the ankle presented a 6‐fold greater risk of not improving in terms of ROM compared with the elbow and knee. RS affords effective treatment of chronic haemophilic synovitis. RS is effective in all patient groups, independently of the presence of circulating inhibitor antibody, the type of joint involved, the degree of synovial membrane hypertrophy and the presence of radiographic findings of joint degeneration (arthropathy).     

How safe is primary knee replacement surgery? Perioperative complication rates in Northern Illinois, 1993–1999

Objective

To describe inpatient complications for primary total knee replacement (TKR) in a period of rapidly growing orthopedic surgery capacity, declining length of stay, and more frequent discharge to rehabilitation facilities.

Methods

Complication incidence according to published coding algorithms was estimated for 35,531 primary TKR admissions of northern Illinois residents to 65 Illinois hospitals. Complication odds were estimated as a function of patients' clinical and sociodemographic status, hospital volume, residency training, TKR length of stay, International Classification of Diseases, Ninth Revision (ICD‐9) coding intensity, and discharges to skilled nursing or rehabilitation facilities.

Results

Primary TKR admissions increased 36% between 1993 and 1999, length of stay declined 43%, average ICD‐9 code use increased 31%, and rehabilitation discharges increased 68%. Major complication rates declined 44% (12.4% to 6.9%; P < 0.0001) over this period, reflecting a 50% reduction in the adjusted odds of complication between 1993 and 1999. There was no association of procedure volume and outcome.

Conclusion

It is likely that the reduction in complications reflects true safety improvements as well as reduced length of stay.

     

Are infections due to resistant pathogens associated with a worse outcome in critically ill patients?

OBJECTIVES: To evaluate the outcome of critically ill patients infected with antimicrobial resistant microorganisms, and to analyse the factors involved in the development of antimicrobial resistance. METHODS: All patients admitted to a 31-bed mixed medico-surgical intensive care unit who developed a nosocomial infection were prospectively followed until discharge or death. RESULTS: Of 949 consecutive patients admitted, 186 developed a nosocomial infection: 79 with an antimicrobial-resistant pathogen and 107 with susceptible strains. The lungs were the main source of infections in both groups. The main resistant microorganisms were Enterobacter aerogenes, methicillin resistant Staphylococcus aureus (MRSA), and Enterobacter cloacae. The main susceptible microorganisms were Enterobacter spp., methicillin susceptible S. aureus (MSSA), and Proteus mirabilis. Patients infected with resistant strains had a longer length of stay prior to infection (9+/-4 vs. 5+/-3 days), longer total length of stay (18+/-16 vs. 11+/-7 days), longer duration of mechanical ventilation (12+/-15 vs. 6+/-7 days), and more severe coagulation, liver, and renal dysfunction (all p<0.05). The maximum degrees of organ failure during the ICU stay, and the respiratory dysfunction, but not infection with a resistant pathogen, were independent predictors for death. Multivariate logistic regression revealed previous use of multiple antibiotics, duration of length of stay prior to infection, and the degree of liver failure as independent factors for development of infection with resistant organisms. CONCLUSIONS: Infection with antimicrobial resistant microorganisms is not an independent predictor for death. The development of antimicrobial resistance is related to the previous use of multiple antibiotics, the ICU length of stay, and the severity of hepatic dysfunction.     

When is enough … enough? Developing consensus of definition of failure of immune tolerance induction in patients with haemophilia and inhibitors

Immune tolerance induction (ITI) is the preferred management of haemophilia A patients who develop high titre inhibitors against factor VIII. However, the optimal ITI regimen, predictors of ITI outcome and definitions of successful and unsuccessful ITI remain unclear. The aim of this project was to develop a consensus on the definition of ITI treatment failure for Australian clinical practice using a modified Delphi approach. Three consecutive surveys were distributed to the directors of 17 haemophilia treatment centres in Australia. Participants were asked to rate their agreement with definitions of ITI treatment failure generated from a literature review. Thirty‐five statements regarding ITI achieved consensus (majority agree or strongly agree) during the three survey rounds. After round 3, four statements achieved majority disagreement, and for two statements no consensus was reached. Our study demonstrates that clinicians in Australia necessitate an arbitrary time to assess ITI failure, but that clinical outcomes of ITI are important in assessing response. Assessment over any 3‐ to 6‐month period without a 20% reduction in inhibitor titre is suggestive of failure, but a reduction in bleeding phenotype alone may be sufficient to continue ITI. Overall, a period of 3 or 5 years of ITI may be required to determine response to ITI. Documentation of improvement in clinical measures, supported by the laboratory features of factor VIII inhibitor levels and pharmacokinetics, is essential in assessing the success of failure of ITI in these patients.