Canadian consensus guidelines on long-term nonsteroidal anti-inflammatory drug therapy and the need for gastroprotection: benefits versus risks

Background  Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used, but are not without risks.
Aim  To provide evidence-based management recommendations to help clinicians determine optimal long-term NSAID therapy and the need for gastroprotective strategies based on an assessment of both gastrointestinal (GI) and cardiovascular (CV) risks.
Methods  A multidisciplinary group of 21 voting participants revised and voted on the statements and the strength of evidence (assessed according to GRADE) at a consensus meeting.
Results  An algorithmic approach was developed to help manage patients who require long-term NSAID therapy. The use of low-dose acetylsalicylic acid in patients with high CV risk was assumed. For patients at low GI and CV risk, a traditional NSAID alone may be acceptable. For patients with low GI risk and high CV risk, full-dose naproxen may have a lower potential for CV risk than other NSAIDs. In patients with high GI and low CV risk, a COX-2 inhibitor plus a proton pump inhibitor (PPI) may offer the best GI safety profile. When both GI and CV risks are high and NSAID therapy is absolutely necessary, risk should be prioritized. If the primary concern is GI risk, a COX-2 inhibitor plus a PPI is recommended; if CV risk, naproxen 500 mg b.d. plus a PPI would be preferred. NSAIDs should be used at the lowest effective dose for the shortest possible duration.
Conclusion  More large, long-term trials that examine clinical outcomes of complicated and symptomatic upper and lower GI ulcers are needed.     

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea–hypopnoea index (AHI) 5–15 h^?1] and 40 controls (AHI <5 h^?1). Serum concentrations of pro‐ and anti‐inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non‐steroidal anti‐inflammatory medication, the mean level of tumour necrosis factor‐α was significantly elevated (1.54 versus 1.17 pg mL^?1, P = 0.004), whereas the level of interleukin‐1β (IL‐1β) was reduced (0.19 versus 0.23 pg mL^?1, P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti‐inflammatory cytokines, interleukin‐10 (1.28 versus 0.70 pg mL^?1, P < 0.001) and interleukin‐1 receptor antagonist (478 versus 330 pg mL^?1, P = 0.003) were elevated in the OSA group. The concentrations of C‐reactive protein increased, but IL‐1β decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro‐inflammatory, but also with the anti‐inflammatory systems.     

Thrombin generation in vitro in the presence of by-passing agents in siblings with severe haemophilia A

Summary.  Previous data have shown an inter-individual difference in the thrombin generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA^® and NovoSeven^®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL⁻¹ (FEIBA^®) and 130.7 ± 54.9 mmol mL⁻¹ (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL⁻¹ (FEIBA^®) and 142.8 ±53.6mmol mL⁻¹ (rFVIIa) ( P  = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families ( P  < 0.001 for both FEIBA^® and NovoSeven^®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.     

Prognostic value of the ankle‐brachial index in elderly patients with a stable chronic cardiovascular event

Summary. Background and Objectives: Patients with polyvascular arterial disease have a greater risk of suffering a new atherothrombotic episode than those with involvement of only one vascular territory. We have studied the predictive prognostic value of the detection of non‐diagnosed peripheral arterial disease, determined by measuring the ankle‐brachial index in a population of elderly patients with stable chronic cardiac or cerebrovascular disease. Methods: This was a multicenter, prospective cohort study with consecutive inclusion of patients between 65 and 85 years of age with a previous atherothrombotic event, but without previously established peripheral arterial disease. Results: A total of 1096 patients were evaluated during 11.7 (± 2.2) months of follow‐up. An ankle‐brachial index of < 0.9 was observed in 29.9% and > 1.4 in 6.9%. The detection of an ankle‐brachial index < 0.9 was clearly associated with the presence of a combined primary event of cardiovascular death and non‐fatal cardiovascular event [HR 1.99 (95% CI, 1.49–2.66; P < 0.001)]. There was also a significant relationship between ankle‐brachial index > 1.4 and total (P = 0.001) or cardiovascular (P = 0.020) deaths. The predictive value of both ranges of the ankle‐brachial index was maintained after adjusting for age, sex, diabetes mellitus, vascular territory, macroalbuminuria or glomerular filtration rate. Conclusions: The detection of non‐diagnosed peripheral arterial disease in patients with stable coronary or cerebrovascular events identifies a very high risk population that might benefit from more intensive treatment.     

Infertility and subfecundity in population-based samples from Denmark, Germany, Italy, Poland and Spain

Background: No uniform data which give basic Information onthe societal burden of infertility and subfecundity exists inEurope. Methods: In a population-based survey the prevalenceof subfecundity was ascertained by means of a standardized interviewwith women in Denmark, Germany, Poland, Italy and Spain. Thetime of unprotected intercourse (TUI) either leading or notleading to pregnancy was applied as a uniform measure of fecundity.Population-based samples of women 25–44 years of age wererecruited. Results: Altogether 6,630 women participated in thestudy. With regard to the first pregnancy, 19% of all coupleshad a TUI of more than 12 months, which is within the rangeof most previous findings. Regarding the most recent and firstTUI in individual lives, if it had occurred within previous5 years, 23.4% overall did not conceive within 12 months (inPoland 33.3%, in north Italy and Germany 26.2%, in Denmark 23.3%,in Spain 18.6% and in south Italy 14.8%). Secondary subfecunditywas more prevalent in Poland. When stratifying for planningof a pregnancy, the differences between countries diminished,particularly for the most recent TUI. However, the pattern ofa higher prevalence of subfecundity in Poland, north Italy,Denmark and Germany and a lower prevalence (<20%) in Spainand south italy remains. Conclusions: Important differencesin the prevalence of subfecundity exist between the six Europeanregions investigated. Comparisons should first consider TUIsor planned TUIs to reduce the impact of distorting factors,which are mainly due to differing cultures of family planningin Europe.     

中央人口资源环境工作座谈会在北京召开

<正> 据新华社报道,中央人口资源环境工作座谈会2001年3月11日上午在人民大会堂举行。中共中央总书记、国家主席江泽民主持座谈会并发表重要讲话。党和国家领导人李鹏、朱镕基、李瑞环、胡锦涛、魏健行、李岚清等出席会座谈会。 江泽民总书记在座谈会上强调指出,今后一段时