Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Hyper IgD syndrome and type AA amyloidosis.

Contains fulltext : 80421.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 29 januari 2009Promotores : Meer, J.W.M. van der, Drenth, J.P.H. Co-promotor : Simon, A.179 p

Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model.

Contains fulltext : 48588.pdf (publisher's version ) (Open Access)BACKGROUND: Hyper-IgD and periodic fever syndrome (HIDS) is an hereditary autoinflammatory syndrome, characterised by recurrent inflammatory attacks. Treatment of HIDS is difficult, although simvastatin is beneficial and etanercept might be effective. Studying the treatment of a rare periodic syndrome is complicated by the varying frequency and severity of symptoms and low prevalence. Our aim was to develop a system of clinical observations to evaluate effectiveness of treatment-on-demand. METHODS: Seven fever episodes in three HIDS patients were monitored, with and without administration of etanercept or anakinra. We developed a clinical score, which includes 12 symptoms. In one patient, inflammatory attacks were provoked by vaccination. RESULTS AND CONCLUSIONS: At the onset of an attack, all patients reported a clinical score between 20 and 25. The score was used to quantify severity and define the end of an attack. Reproducible monitoring of inflammatory episodes was difficult, even in this pilot study. The effect of early administration of etanercept was variable. In one patient, a fever episode could be readily provoked within 12 to 24 hours by vaccination. In this patient, the IL-1ra analogue anakinra was more successful in aborting the inflammatory attack than etanercept. We propose that this vaccination model will allow evaluation of treatment-on-demand in a controlled setting

Hypogammaglobulinaemia: cumulative experience in 49 patients in a tertiary care institution

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Hereditary periodic fever and reactive amyloidosis.

Contains fulltext : 47764.pdf (publisher's version ) (Closed access)Hereditary periodic fever syndromes (HPF) are a group of diseases characterised by recurrences of fever and inflammation separated by symptom-free intervals. Familial Mediterranean fever (FMF) is the most frequent entity within this group of disorders which further consists of hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS), tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated periodic syndrome (CAPS). In recent years the causative genes have been identified. Reactive amyloidosis is a severe complication of HPFs. This is caused by deposition of fibrils that consist of the proteolytically cleaved acutephase protein serum amyloid A (SAA). Several factors have been identified that modulate the risk for developing amyloidosis, including SAA concentrations, polymorphisms in the SAA gene and ethnic origin. Furthermore, the risk of developing amyloidosis varies widely between the different HPFs. Colchicine is the cornerstone in the management of FMF, as it reduces the severity and frequency of attacks and is also effective in preventing amyloidosis. In the other HPFs, the introduction of anticytokine-based therapies is a promising new option in treating these inflammatory conditions and they potentially can prevent amyloidosis

AL amyloidosis enhances development of amyloid A amyloidosis.

Contains fulltext : 52125.pdf (publisher's version ) (Closed access

Two patients with recurrent fever and wine red discolouration of the eyelids.

Contains fulltext : 59192.pdf (publisher's version ) (Closed access

Prevalence of drug-drug interactions in the era of HIV integrase inhibitors: a retrospective clinical study

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