A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload

This was a 24-week, multicenter phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in < 5% of patients. Mean serum creatinine did not change significantly from Baseline or between dose groups. Transaminases wer increased in 8 (16%), three of whom acquired HCV on-study from a single blood bank while five had an abnormal baseline ALT. The 24 week mean change in liver iron concentration (ΔLIC) at 14.5 mg/kg/d was +3.1 mg/g (dw); 29% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was -0.3 mg/g (dw); 44% achieved a decrease in LIC (P < .03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compare favorably to other oral chelators.     

Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience

We retrospectively analysed the outcome of consecutive children with idiopathic severe aplastic anaemia in the United Kingdom who received immunosuppressive therapy (IST) or matched unrelated donor (MUD) haematopoietic stem cell transplantation (HSCT). The 6-month cumulative response rate following rabbit antithymocyte globulin (ATG)/ciclosporin (IST) was 32·5% (95% CI 19·3-46·6) (n = 43). The 5-year estimated failure-free survival (FFS) following IST was 13·3% (95% confidence interval [CI] 4·0-27·8). In contrast, in 44 successive children who received a 10-antigen (HLA-A, -B, -C, -DRB1, -DQB1) MUD HSCT there was an excellent estimated 5-year FFS of 95·01% (95% CI 81·38-98·74). Forty of these children had failed IST previously. HSCT conditioning was a fludarabine, cyclophosphamide and alemtuzumab (FCC) regimen and did not include radiotherapy. There were no cases of graft failure. Median donor chimerism was 100% (range 88-100%). A conditioning regimen, such as FCC that avoids total body irradiation is ideally suited in children. Our data suggest that MUD HSCT following IST failure offers an excellent outcome and furthermore, if a suitable MUD can be found quickly, MUD HSCT may be a reasonable alternative to IST.     

Psychiatric morbidity among HIV-infected children and adolescents in a resource-poor Kenyan urban community

The course of HIV/AIDS in children has been transformed from an acute to a chronic one with the advent of Anti-Retroviral Therapy. The aim of this study was to determine the prevalence and pattern of psychiatric morbidity in HIV-infected children and adolescents between 6 and 18 years of age and the relationship between their socio-demographic factors, immune suppression and psychiatric morbidity. The study was conducted at a paediatric HIV clinic in Nairobi, between February and April 2010. One hundred and sixty-two HIV-infected children and adolescents aged between 6 and 18 years and their guardians were interviewed. Seventy-nine (48.8%) of the study participants were found to have psychiatric morbidity. The most prevalent Diagnostic Statistical Manual, 4th Edition TR psychiatric disorders were: Major depression (17.8%), Social phobia (12.8%), Oppositional Defiant Disorder (12.1%) and Attention Deficit Hyperactivity Disorder (12.1%). Twenty-five per cent of the study participants had more than one psychiatric disorder. The prevalence of psychiatric morbidity in HIV-infected children is higher than that found in children in the general population. There is therefore a need to integrate psychiatric services into the routine care of HIV-infected children.     

The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater's assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater's assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients.     

Cardiac risks and management of complications in pregnant women with congenital heart disease

There are a growing number of women with congenital heart disease reaching adulthood and contemplating and/or undergoing pregnancy. However, pregnancy imposes hemodynamic stress on the heart and this can result in maternal, fetal and neonatal complications. Most women with congenital heart disease do well during pregnancy, but some women with high-risk cardiac lesions will not tolerate the hemodynamic changes of pregnancy. Physicians must be aware of the potential risks for the mother both during and after pregnancy, the risks to the fetus and neonate, and the risks and benefits of medications and procedures used during pregnancy. For women with complex cardiac conditions, management during pregnancy benefits from multidisciplinary care involving cardiologists with expertise in pregnancy, obstetricians with expertise in maternal fetal medicine, neonatologists and obstetric anesthetists, among others. This review will focus on the cardiac risks faced by women with congenital heart disease; particularly those at high risk, and on management strategies to mitigate risk and address cardiac complications.     

Pelvic organ prolapse surgery in Western Australia: a population-based analysis of trends and peri-operative complications

Introduction and hypothesis

We previously described a declining rate of surgery in the treatment of pelvic organ prolapse (POP) in Western Australia. This paper builds on previous work by examining temporal trends and the post-operative risk of in-hospital complications, following first time incident prolapse surgery in a population-based cohort of women.

Methods

We investigated rates of prolapse surgery between 1988 and 2005 according to age group and concomitant procedure type for 34,509 women whose data were extracted from the WA Data Linkage System. We investigated changes over time in the demographic characteristics of women undergoing surgery and whether the presence of selected concomitant procedures increased the risk of in-hospital complications.

Results

During the study period, 34,509 women underwent an incident surgery for POP. Concomitant hysterectomy was performed in more than half of all surgeries (52.4 %) and a concomitant urinary incontinence (UI) surgery was noted in 25.8 %. 10.9 % of patients experienced a complication of interest, with the highest percentage of complications recorded in women who underwent multi-concomitant surgery. After controlling for age, comorbidity and time period we found that concomitant UI surgery increases in-hospital complications (OR 1.61 95 % CI 1.42–1.83) only in women who have a repair procedure (colporrhaphy and/or enterocele repair). There was no significant effect of concomitant procedures in women who underwent a combined repair and apical prolapse procedure.

Conclusions

Surgery to treat prolapse is common, has low mortality and concomitant surgery only increases complications when combined with simpler prolapse surgery.