Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Evidências sobre o suporte durante o trabalho de parto/parto: uma revisão da literatura Evidence on support during labor and delivery: a literature review

Os efeitos do suporte à mulher durante o trabalho de parto/parto por profissionais de saúde, mulheres leigas e doulas, sobre os resultados maternos e neonatais têm sido avaliados em vários ensaios clínicos randomizados, metanálises e revisões sistemáticas. Este artigo apresenta a revisão desses estudos, enfocando as principais características, o provedor de suporte, a simultaneidade na presença ou não do companheiro/familiares da parturiente durante o trabalho de parto e parto, e os resultados obtidos. Foram incluídos os estudos publicados entre os anos de 1980 e 2004, que contemplam explicitamente os aspectos avaliados. De maneira geral, os resultados do suporte são favoráveis, destacando-se redução da taxa de cesarianas, da analgesia/medicamentos para alívio da dor, da duração do trabalho de parto, da utilização de ocitocina e produzindo aumento na satisfação materna com a experiência vivida. Quando o provedor de suporte não é um profissional de saúde, os benefícios têm sido mais acentuados. Os estudos disponíveis não avaliam o acompanhante escolhido pela parturiente como um provedor de suporte, o que constitui lacuna de conhecimento a ser preenchida.<br>The effects of support for women during labor and delivery provided by health professionals, lay women, and doulas on the maternal and neonatal outcomes have been evaluated through randomized clinical trials, meta-analyses, and systematic reviews. This article presents a review of these studies, focusing on the principal characteristics, support provider, simultaneous presence of the woman's spouse and/or family members during labor and delivery and the outcomes. The analysis included studies published from 1980 to 2004 which explicitly approached these aspects. In general, the results of such support were favorable, highlighting a reduction in the cesarean rate, analgesia/ medication for pain relief, duration of labor, and utilization of oxytocin and an increase in maternal satisfaction with the experience. The benefits were greater when the support provider was not a health professional. The available studies did not evaluate the specific companion chosen by the woman as a support provider, which constitutes a gap in the knowledge that should be filled by future research

Variation in referrals to secondary obstetrician-led care among primary midwifery care practices in the Netherlands: a nationwide cohort study

Contains fulltext : 154413.pdf (publisher's version ) (Open Access)BACKGROUND: The primary aim of this study was to describe the variation in intrapartum referral rates in midwifery practices in the Netherlands. Secondly, we wanted to explore the association between the practice referral rate and a woman's chance of an instrumental birth (caesarean section or vaginal instrumental birth). METHODS: We performed an observational study, using the Dutch national perinatal database. Low risk births in all primary care midwifery practices over the period 2008-2010 were selected. Intrapartum referral rates were calculated. The referral rate among nulliparous women was used to divide the practices in three tertile groups. In a multilevel logistic regression analysis the association between the referral rate and the chance of an instrumental birth was examined. RESULTS: The intrapartum referral rate varied from 9.7 to 63.7 percent (mean 37.8; SD 7.0), and for nulliparous women from 13.8 to 78.1 percent (mean 56.8; SD 8.4). The variation occurred predominantly in non-urgent referrals in the first stage of labour. In the practices in the lowest tertile group more nulliparous women had a spontaneous vaginal birth compared to the middle and highest tertile group (T1: 77.3%, T2:73.5%, T3: 72.0%). For multiparous women the spontaneous vaginal birth rate was 97%. Compared to the lowest tertile group the odds ratios for nulliparous women for an instrumental birth were 1.22 (CI 1.16-1.31) and 1.33 (CI 1.25-1.41) in the middle and high tertile groups. This association was no longer significant after controlling for obstetric interventions (pain relief or augmentation). CONCLUSIONS: The wide variation between referral rates may not be explained by medical factors or client characteristics alone. A high intrapartum referral rate in a midwifery practice is associated with an increased chance of an instrumental birth for nulliparous women, which is mediated by the increased use of obstetric interventions. Midwives should critically evaluate their referral behaviour. A high referral rate may indicate that more interventions are applied than necessary. This may lead to a lower chance of a spontaneous vaginal birth and a higher risk on a PPH. However, a low referral rate should not be achieved at the cost of perinatal safety