SUMMARY The paper addresses the evergreen problem of construction of regressors for use in least squares multiple regression. In the context of a general sequential procedure for doing this, it is shown that, with a particular objective criterion for the construction, the procedures of ordinary least squares and principal components regression occupy the opposite ends of a continuous spectrum, with partial least squares lying in between. There are two adjustable ‘parameters’ controlling the procedure: ‘alpha’, in the continuum [0, 1], and ‘omega’, the number of regressors finally accepted. These control parameters are chosen by cross‐validation. The method is illustrated by a range of examples of its application.

Brief Report IntroductionProvision of safe and effective anticoagulation for pregnant women with mechanical heart valves is a challenging management problem. All current anticoagulation regimens are associated with maternal thromboembolism (TE) and/or bleeding. Vitamin K antagonist (VKA) therapy throughout pregnancy results in the lowest observed risk of TE (3.9%). However, VKA use is associated with fetal anomaly rates of 6.4%, fetal death of 12% and neurodevelopmental problems.1,2 The rate of TE with unfractionated heparin (UFH) is high at 25% if used throughout pregnancy and 9% if used for the first trimester. 1 Therapeutic dose LMWH is an attractive alternative to VKAs and UFH. However, in the HIP-CAT study which compared enoxaparin with sequential UFH and warfarin in pregnant women with mechanical valves, 2/7 women receiving therapeutic dose enoxaparin 1 mg/kg 12 hourly developed fatal valve thrombosis. 3 The incidence of TE using LMWH in this setting is not known because of the limited data available, but James et al. found an overall TE rate of 22% and a maternal mortality of 4%. 4 In another review, Oran et al. found an overall incidence of valve thrombosis of 8.64% (8/81) and the overall TE rate 12.35% (10/81).5 However, 9 of these 10 patients received a fixed dose of LMWH, and in 2 of these a low fixed dose was used. Among 51 pregnancies where antiXa levels were monitored, only one patient was reported to have had TE. The American College of Chest Physicians (ACCP) advises that there are insufficient data for definitive recommendations on how best to anticoagulate women with mechanical valves in pregnancy, in view of concerns for fetal well-being with warfarin therapy and the possible poorer efficacy of subcutaneous UFH and LMWH in preventing maternal TE. 6 Recommendations have included adjusted dose LMWH throughout pregnancy to keep a 4 h post-dose anti-Xa level of 1.0-1.2 IU/mL although updated ACCP guidelines recommend adjusted dose LMWH to achieve the manufacturer's peak anti-Xa level 4 h post subcutaneous injection (approximately 1.0 IU/mL) with consideration of LDA in women with prosthetic heart valves at particularly high risk of thrombosis. 7Against this background, we conducted a prospective audit of our experience with the use of our dose-adjusted regimen of high intensity LMWH in pregnant women with mechanical heart valves, and documented TE and bleeding complications, pregnancy outcome, as well as anti-Xa levels throughout their pregnancies. Design and MethodsAll pregnancies in women with mechanical heart valves between 2001 and 2007 who received LMWH were included. The use of standard dose low molecular weight heparin (LMWH) to anticoagulate women with mechanical valves in pregnancy is associated with morbidity and mortality. We conducted a prospective audit of the use of adjusted dose high intensity LMWH in 12 pregnancies in 11 women with prosthetic heart valves. LMWH ± low-dose aspirin was started at therapeutic-dose with monitoring of anti-Xa levels to achieve a target level of 1.0-1.2 ...

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In patients with CHD and residual RVOT lesions, the outcome of pregnancy is good. Patients with moderate-to-severe PR were at risk for symptomatic RHF only if additional risk factors were present. When treated by a multidisciplinary team, maternal and foetal outcome was good. The general recommendation that pulmonary valve replacement should be undertaken prior to pregnancy in patients with moderate-to-severe PR and RV dilatation needs to be reconsidered.