Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies.

Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty-five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato-oncological diagnosis. Following immunological assessment and intervention, a 4.39-fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30-fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen-specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen-specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.

Abnormal chondrocyte apoptosis in the cartilage growth plate is influenced by genetic background and deletion of CHOP in a targeted mouse model of pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by mutations in cartilage oligomeric matrix protein (COMP) and characterised by short limbed dwarfism and early onset osteoarthritis. Mouse models of PSACH show variable retention of mutant COMP in the ER of chondrocytes, however, in each case a different stress pathway is activated and the underlying disease mechanisms remain largely unknown. T585M COMP mutant mice are a model of moderate PSACH and demonstrate a mild ER stress response. Although mutant COMP is not retained in significant quantities within the ER of chondrocytes, both BiP and the pro-apoptotic ER stress-related transcription factor CHOP are mildly elevated, whilst bcl-2 levels are decreased, resulting in increased and spatially dysregulated chondrocyte apoptosis. To determine whether the abnormal chondrocyte apoptosis observed in the growth plate of mutant mice is CHOP-mediated, we bred T585M COMP mutant mice with CHOP-null mice to homozygosity, and analysed the resulting phenotype. Although abnormal apoptosis was alleviated in the resting zone following CHOP deletion, the mutant growth plates were generally more disorganised. Furthermore, the bone lengths of COMP mutant CHOP null mice were significantly shorter at 9 weeks of age when compared to the COMP mutant mice, including a significant difference in the skull length. Overall, these data demonstrate that CHOP-mediated apoptosis is an early event in the pathobiology of PSACH and suggest that the lack of CHOP, in conjunction with a COMP mutation, may lead to aggravation of the skeletal phenotype via a potentially synergistic effect on endochondral ossification.

Assortativity coefficient-based estimation of population patterns of sexual mixing when cluster size is informative.

OBJECTIVES: Population sexual mixing patterns can be quantified using Newman's assortativity coefficient (r). Suggested methods for estimating the SE for r may lead to inappropriate statistical conclusions in situations where intracluster correlation is ignored and/or when cluster size is predictive of the response. We describe a computer-intensive, but highly accessible, within-cluster resampling approach for providing a valid large-sample estimated SE for r and an associated 95% CI. METHODS: We introduce needed statistical notation and describe the within-cluster resampling approach. Sexual network data and a simulation study were employed to compare within-cluster resampling with standard methods when cluster size is informative. RESULTS: For the analysis of network data when cluster size is informative, the simulation study demonstrates that within-cluster resampling produces valid statistical inferences about Newman's assortativity coefficient, a popular statistic used to quantify the strength of mixing patterns. In contrast, commonly used methods are biased with attendant extremely poor CI coverage. Within-cluster resampling is recommended when cluster size is informative and/or when there is within-cluster response correlation. CONCLUSIONS: Within-cluster resampling is recommended for providing valid statistical inferences when applying Newman's assortativity coefficient r to network data.

Wake me up when there's a crisis: progress on state pandemic influenza ethics preparedness.

We assessed the progress since 2005 of state plans for pandemic influenza and found that 7 states had recommended steps to further clarify ethical processes or decisions; 6 states had made some progress but almost exclusively in hospital preparedness. Having a high-level public health leader, such as a health department director, committed to ethics was the key determinant of progress. Some state health departments may be destined to gain an appreciation for ethics through ethical mishaps.

Perceived neighborhood safety and depressive symptoms among African American crack users.

This study examined the association between perceived neighborhood safety and depressive symptoms among 443 out-of-treatment African American crack cocaine users interviewed between 2000 and 2002 in North Carolina and tested the regression of depression on perceived neighborhood safety and common predictors of depression. Perceived neighborhood safety was an important predictor of depressive symptoms in models that adjusted for other correlates of depression. The findings are limited by the cross-sectional nature of the data and the complex etiology and course of depression. Additional research is needed to clarify the relationship between perceived neighborhood safety and depression. The study was supported by the National Institute on Drug Abuse.

Alcohol, cannabis, and methamphetamine use and other risk behaviours among Black and Coloured South African women: a small randomized trial in the Western Cape.

BACKGROUND: There is a pressing need for brief behavioural interventions to address the intersection of high HIV prevalence, increasing substance use, and high-risk sex practices among South African women. The primary aim of this pilot, randomized trial was to examine whether an adapted evidence-based intervention would be equally, more, or less effective at reducing HIV risk behaviours when delivered using an individual or group format. The secondary aim was to examine differences between Black and Coloured South African women across pre- and post-intervention measures of alcohol and illicit drug use and sex risk behaviours. METHODS: The Cape Town Women's Health CoOp was adapted from an evidence-based intervention known as the Women's CoOp. Study participants included Black (n=60) and Coloured (n=52) women living in the township communities of Cape Town, South Africa, who reported using illicit drugs and alcohol. RESULTS: Coloured women reported greater methamphetamine use (13 days in the past 30 days) and Black women reported mostly cannabis use (27 days in the past 30 days). Although both groups reported having unprotected sex under the influence of alcohol and/or other drugs, Black women reported greater condom use and having one partner; Coloured women reported having more than one sex partner. One-month post-intervention assessments indicated significant reductions in substance use and sex risk behaviours. After controlling for baseline measures, there were no significant differences between the two intervention conditions. CONCLUSION: Significant differences in risk behaviours were observed between Black and Coloured South African women. However, both ethnic groups were responsive to the adapted intervention and no differences were found by intervention assignment. These findings support the assertion that group interventions may be more cost-effective in reaching at-risk women in resource-scarce environments. Larger studies are needed to show efficacy and effectiveness of woman-focused group prevention interventions.

Health care-based interventions for women who have experienced sexual violence: a review of the literature.

Thirty publications that evaluated health care-based interventions for women who experienced sexual violence were reviewed. The findings highlight that clinicians often need training in the provision sexual assault care, and that not all emergency departments have sexual assault care protocols. Studies examining effectiveness found that Sexual Assault Nurse Examiner programs are very helpful, that health care-based sexual assault treatment settings attract more women than do forensic-based settings, that sexual assault survivors often prefer a combination of medication and counseling treatment, and that preexam administration of a video explaining the collection of forensic evidence may reduce women's stress during the procedure. Studies on postexposure HIV prophylaxis found that many women did not complete the treatment regimen, often because of side effects. Emergency contraception to prevent postrape pregnancy is not consistently offered to women. Only one study reported on abortion as part of the range of sexual assault services.