A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS < or = 12 and treatment costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported in 2004 DDK. The expected overall 6-month remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.     

Who gets screened, and where: a comparison of organised and opportunistic mammography screening in Geneva, Switzerland

It is unclear whether introducing organised mammography screening programmes in a population where opportunistic screening is prevalent results in the two types of screening mainly competing against each other or attracting different groups of women. To compare women who participate in organised screening and those who prefer opportunistic screening, we conducted a prospective study of 932 women followed for 8 months after an invitation to participate in the first round of an organised screening programme in Geneva, Switzerland. All women were aged 50-69 years and were due for a mammogram according to local guideline. Of the 932 participants, 11.6% had an organised and 39.4% an opportunistic mammogram during follow-up. Women who were in the stage of contemplation, had favourable attitude toward mammography screening, and perceived their risk of breast cancer to be high were more likely to have a mammogram (either organised or opportunistic). Compared to women who had an opportunistic mammogram, women with an organised mammogram were less positive about screening, less likely to be in maintenance at baseline (adjusted odds ratio (OR), 3.0; 95% confidence interval (CI), 1.7-5.5), to have a history of benign breast disease (OR, 2.4; 95% CI, 1.2-5.1) and to perceive their financial situation as comfortable (OR, 1.7; 95% CI, 1.1-2.8). Although screening uptake was low, the programme appeared to attract women in lower socio-economic strata who did not usually undergo mammography screening.     

Sepiapterin reductase deficiency: clinical presentation and evaluation of long-term therapy

Sepiapterin reductase deficiency has recently been recognized as a treatable, inborn error of pterin metabolism. This investigation is the first long-term clinical study demonstrating impressive positive, long-term effects of treatment in two cases of sepiapterin reductase deficiency after 2 and 5 years of treatment respectively. The two patients were not diagnosed before 7 and 13 years of age. These results highlight the importance of cerebrospinal fluid neurotransmitter investigations in childhood encephalopathy, in cases of unexplained early-onset neurologic handicap. Such a widened approach to the diagnostic efforts in early-onset encephalopathy with motor delay during childhood is important, as we have at our disposal a simple and effective treatment.     

Intra-individual comparison of sentinel lymph node scintigraphy on the day of injection and on the following day in breast cancer

OBJECTIVES: To compare, intra-individually, the detection rates of sentinel node on lymphoscintigraphy performed on the day of injection (D0) and on the following day (D1) in breast carcinoma. We also compared 2-day and 1-day protocols in the two groups of patients. METHODS: The 2-day and 1-day protocols included 76 patients in group 1 and 23 patients in group 2. Patients from group 1 underwent lymphoscintigraphy twice--at 2 h (lymphoscintigraphy 1) and 18 h (lymphoscintigraphy 2) post-injection at four sites periareolar using 99mTc sulfur colloid. Patients from group 2 underwent lymphoscintigraphy only at 2 h post-injection. The detection rates and the number of sentinel nodes were compared in the two lymphoscintigraphy examinations for group 2. RESULTS: The detection rate on lymphoscintigraphy in group 1 was 92% at D0 and 96% at D1. The overall agreement between lymphoscintigraphy 1 and lymphoscintigraphy 2 was 69/76 (91%). In 2/76 women, the sentinel node disappeared at D1 on lymphoscintigraphy, but remained detectable during surgery, and in 5/76 women, the sentinel node appeared at D1 on lymphoscintigraphy. The mean number of sentinel nodes detected on lymphoscintigraphy was 2.05+/-0.14 at D0 and 1.76+/-0.11 at D1 (P=0.004) in group 2, the detection rate of the sentinel node was 20/23 (87%). CONCLUSION: Our study demonstrated that for patients undergoing the 2-day protocol for sentinel node procedure in early stage breast cancer, the optimal imaging time would be to perform lymphoscintigraphy 1 h after injection, with the possibility of imaging patients the following day in cases where lymphoscintigraphy was negative.     

Impact of information about risks and benefits of cancer screening on intended participation

BackgroundProviding comprehensive information about the risks and benefits of cancer screening is ethically necessary, but information about risks may decrease participation. This study explored the impact of information on intended participation using a randomised factorial design.MethodsWe conducted a mail survey of 2333 adults living in Geneva, Switzerland. Each participant was given one randomly chosen version of a scenario that described a hypothetical cancer screening test, and was asked whether he or she would accept to undergo screening. The versions varied in terms of the amount of information about risks and benefits.ResultsRespondents who received information about risks associated with screening were more likely to refuse participation (odds ratio 2.6 (95% confidence interval (CI) 2.0–3.5)) than those who received minimal information. In contrast, information about benefits had no impact on intended participation (odds ratio 1.0 (95% CI 0.8–1.2)). The impact of information about risks was significantly stronger in women than in men, in respondents who were in poorer health, who have had a doctor visit in the past 6 months, those who have had a cancer screening test in the past 3 years, and those who reported a high desire for autonomy in medical decisions.ConclusionsInforming potential participants about the risks of screening may reduce participation rates. Enhanced information about the benefits of screening does not counterbalance this effect.     

Effects of the CCR5-Δ32 Mutation on Hepatitis C Virus-Specific Immune Responses in Patients with Haemophilia

In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-Δ32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-γ and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-Δ32 heterozygous n = 5 and CCR5-Δ32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, –4 and –5 was studied. Overall IFN-γ responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-Δ32 carriers (0.6 versus 0.24 SFC/10⁴ PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-Δ32 may potentially result in subtle reduction of HCV specific IFN-γ responses in anti-HCV-positive haemophiliac patients.     

Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in BALB/c mice induce specific humoral and cellular Th1/Th2-like immune responses

We investigated the immune response induced by mucosal immunization of BALB/c mice with virus-like particles (VLPs) of a genogroup II norovirus, Dijon171/96 virus, produced in the baculovirus system. VLPs administered alone by the intranasal route induced a high serum antibody response as well as fecal IgA, which were enhanced when the heat-labile Escherichia coli toxin or its non toxic mutant LT(R192G) was coadministered. In these conditions, the oral route was also efficient. Cytokine production by cells from different lymphoid tissues was then assessed after in vitro restimulation. A Th1/Th2-like response was observed in cervical lymph node and Peyer's patch (PP) cell cultures from mice intranasally or orally immunized with either adjuvant indicating that, on the assumption that T cells are the primary cells producing the cytokines after in vitro restimulation, specific T lymphocytes are present in the intestine after intranasal immunization.     

The Histone Methyltransferase SETDB1 Controls T Helper Cell Lineage Integrity by Repressing Endogenous Retroviruses

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