Simvastatin,transdermal patch,and oral estrogen-progestogen preparation in early-postmenopausal hypercholesterolemic women: a randomized,placebo-controlled clinical trial

Hormone replacement therapy (HRT) seems to have a favorable influence on the plasma lipid profile. Only a few investigations have examined the effects of HRT versus hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors. We compared the relative effects of different hypolipidemic strategies on lipoproteins and coagulative parameters in women with recent-onset spontaneous menopause. In this 24-week, placebo-controlled trial, 60 consecutive healthy women aged >/= 45 years, with amenorrhea from 6 to 60 months (mean, 1.9 +/- 1.4 years), serum follicle stimulating hormone (FSH) greater than 40 U/L, and slight to moderate hypercholesterolemia (low-density lipoprotein-cholesterol [LDL-C] 160 to 250 mg/dL, high-density lipoprotein-cholesterol [HDL-C] < 75 mg/dL, and triglycerides < 200 mg/dL) were enrolled and randomized to dietetic advice (placebo group), simvastatin 10 mg, 0.625 mg of conjugated equine estrogen (CEE), or 50 microg estrogen transdermal patch (ETP). In the latter 2 cases, the progestative nomegestrol was added to estrogens (days 17 to 28 of the cicle). Lipoprotein parameters were evaluated after separating very-low-density lipoproteins (VLDLs) by ultracentrifugation, while fasting glucose and insulin, homocysteine, and hemocoagulative parameters were determined in plasma. Fifty-four patients completed the trial. Total cholesterol (TC) and LDL-C significantly decrased in the simvastatin (-62 mg/dL [-20%] and -72 mg/dL [-30%], respectively), CEE (-42 mg/dL [-13%] and -45 mg/dL [-18%]), and ETP (-30 mg/dL [-10%] and -26 mg/dL [-11%]) groups compared to baseline, but only simvastatin showed an effect significantly superior to diet alone. Apolipoprotein (Apo) B was decreased by simvastatin (-25%, P <.001) and by CEE (-10%, P <.05); again, simvastatin was more effective than either diet or ETP. Triglyceride concentration and VLDL-C were unmodified by treatments. HDL-C and Apo A-I significantly increased in the simvastatin group (+18% and +8%, respectively), while HDL-C was unmodified by both HRT regimens and Apo A-I was reduced by ETP treatment (-17%); lipoprotein[a] (Lp[a]) was decreased by both HRTs (-38%, P <.05, and -22%, P =.07, for CEE and ETP, respectively). Among coagulative parameters, plasminogen activator inhibitor-1 (PAI-1) was significantly reduced by CEE (-29%, P <.05) but not ETP treatment (+16%, P = not significant), while fibrinogen, antithrombin, and homocysteine were unaffected by therapy. Thus, HRT, particularly CEE, seems well tolerated and moderately effective in improving the lipid pattern and, perhaps, the coagulative/fibrinolytic balance in postmenopausal hypercholesterolemic women; it may represent a therapeutic option in slightly dyslipidemic subjects. Statins are preferred in case of more severe disease.     

Theoretical arguments for the discounting of health consequences: where do we go from here?

Despite the theoretical arguments presented in the literature regarding discounting over the last 25 years, no satisfactory reply has yet been offered to the question of whether health consequences have to be discounted at the same rate as monetary consequences in the economic evaluation of health programmes or interventions designed to improve health. Against this background, the main objective of this paper was to review and systemise these theoretical arguments, with the aim of determining whether any of the positions identified can be accepted without reservation. Having determined that this is not possible, we investigated the rationality of discounting in the literature and, on this basis, propose a potential way to resolve the problem. Thus, we argue that the relationship between the discount of monetary and health consequences has to be determined in an indirect manner, by reference to the relationship maintained by the individual time preference rates for health and money in the context of private and social choice. Although this proposal moves the debate into the empirical field, its advantages must be weighed against the difficulties associated with the estimation of the time preferences.     

Medicare spending for injured elders: are there opportunities for savings?

Claims for injury care provided to aged fee-for-service (FFS) beneficiaries cost Medicare more than $8 billion in 1999, almost 6 percent of Medicare claims spending for elders. More than one-fifth of aged FFS beneficiaries had an injury that resulted in a claim. Fractures, which were experienced by one in seventeen aged beneficiaries, were responsible far 67 percent of total injury claims expenses. Medicare could realize substantial savings if these injuries could be prevented; the program should consider underwriting effective prevention activities.     

High bone turnover in Muslim women with vitamin D deficiency

OBJECTIVE: To measure bone turnover in Muslim women with vitamin D deficiency. DESIGN: A cross-sectional study of a random sample of Muslim women aged 20-65 years, evaluated over a 6-month period from November 1999 to April 2000. SETTING AND PARTICIPANTS: 146 women living in an urban community in south-western Sydney with adequate opportunities for sun exposure. MAIN OUTCOME MEASURES: Bone turnover as measured by urinary deoxypyridinoline (DPYD) excretion rates; and vitamin D status as determined by 25-hydroxyvitamin D (25OHD) levels, serum calcium levels and parathyroid hormone (PTH) concentrations. RESULTS: We analysed data on 119 Muslim women (mean [SEM] age, 46.6 [1.1] years) who met the inclusion criteria. There were 81 (68.1%) women with serum 25OHD levels < 30 nmol/L (defined as "severe" vitamin D deficiency). Fifty-five (46.2%) women had evidence of high bone turnover (urinary DPYD excretion > 6.5 nmol/mmol creatinine). The women with "severe" vitamin D deficiency had significantly higher serum PTH levels (7.3 [0.3] v 5.4 [0.5] pmol/L; P = 0.001) and higher urinary DPYD excretion (7.2 [0.3] v 5.4 [0.2] nmol/mmol creatinine; P = 0.003) than women with serum 25OHD levels > or= 30 nmol/L. No significant differences were seen in their ages, menopausal status or serum calcium and phosphate measurements. The risk of developing high bone turnover was significantly greater in the women with "severe" vitamin D deficiency (relative risk = 5.52; 95% CI, 2-14.8; chi(2 )= 12.95; P = 0.0003). CONCLUSION: High bone turnover occurs in Muslim women with vitamin D deficiency.     

Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.     

Partial Epilepsy of Long Duration: Changing Semiology with Age

There are few data on changing patterns of localization-related epileptic syndromes with time and particularly on changes in seizure semiology as patients age. We retrospectively reviewed 53 patients aged >60 years who had had partial epileptic seizures for a mean duration of 44 years. In 20 patients, seizures became progressively less elaborate and briefer with time. In 29 patients, seizures were unchanged. In four patients, seizures worsened, with the appearance of drop attacks, secondarily generalized seizures, increasing drug resistance, and mental deterioration. These latter 4 patients had cerebrovascular disease with multiple strokes.     

Iron-biofortified rice improves the iron stores of nonanemic Filipino women

Iron deficiency is endemic in much of the world, and food system-based approaches to eradication may be viable with new plant breeding approaches to increase the micronutrient content in staple crops. It is thought that conventional plant breeding approaches provide varieties of rice that have 400-500% higher iron contents than varieties commonly consumed in much of Asia. The efficacy of consuming high-iron rice was tested during a 9-mo feeding trial with a double-blind dietary intervention in 192 religious sisters living in 10 convents around metro Manila, the Philippines. Subjects were randomly assigned to consume either high-iron rice (3.21 mg/kg Fe) or a local variety of control rice (0.57 mg/kg Fe), and daily food consumption was monitored. The high-iron rice contributed 1.79 mg Fe/d to the diet in contrast to 0.37 mg Fe/d from the control rice. The 17% difference in total dietary iron consumption compared with controls (10.16 +/- 1.06 vs. 8.44 +/- 1.82 mg/d) resulted in a modest increase in serum ferritin (P = 0.10) and total body iron (P = 0.06) and no increase in hemoglobin (P = 0.59). However, the response was greater in nonanemic subjects for ferritin (P = 0.02) and body iron (P = 0.05), representing a 20% increase after controlling for baseline values and daily rice consumption. The greatest improvements in iron status were seen in those nonanemic women who had the lowest baseline iron status and in those who consumed the most iron from rice. Consumption of biofortified rice, without any other changes in diet, is efficacious in improving iron stores of women with iron-poor diets in the developing world.     

Gravid uterus exteriorization at cesarean delivery for prenatally diagnosed placenta previa-accreta

Uterine exteriorization during fetal surgery permits hysterotomy away from anterior placental implantations. We employed this technique in two cesarean deliveries for anterior placenta previa-accreta, facilitating selective uterine incisions. Exteriorization of the near-term gravid uterus may be a useful adjunct to cesarean delivery for anterior placenta previa-accreta.