Costs and net health effects of contraceptive methods

BACKGROUND: Pregnancy and contraceptive methods both have important health effects that include risks and benefits. The net impact of contraception on women's health has not been reported previously. STUDY DESIGN: This is a cost-utility analysis using a Markov model evaluated by Monte Carlo simulation using the societal perspective for costs. The analysis compared 13 methods of contraception to nonuse of contraception with respect to healthcare costs and quality-adjusted life years (QALYs). Discounting was applied for future costs and health effects. The base-case analysis applies to women of average health and fertility, ranging from 15 to 50 years of age, who are sexually active in a mutually monogamous relationship; smoking rates observed in women of reproductive age were used. Sensitivity analysis extended the analysis to nonmonogamous status and smoking status. RESULTS: Compared with use of no contraception, contraceptive methods of all types result in substantial cost savings over 2 years, ranging from US$5907 per woman for tubal sterilization to US$9936 for vasectomy and health gains ranging from 0.088 QALYs for diaphragm to 0.147 QALYs for depot medroxyprogesterone acetate. Compared with nonuse, even with a time horizon as short as 1 year, use of any method other than sterilization results in financial savings and health gains. Most of the financial savings and health gains were due to contraceptive effects. In a population of patients, even modest increases in the use of the most effective methods result in financial savings and health gains. CONCLUSIONS: Every method of contraception dominates nonuse in most clinical settings. Increasing the use of more effective methods even modestly at the expense of less effective methods will improve health and reduce costs. Methods that require action by the user less frequently than daily are both less costly and more effective than methods requiring action on a daily basis.     

Seasonal congestive heart failure mortality and hospitalisation trends, Quebec 1990-1998

STUDY OBJECTIVE: To describe seasonal congestive heart failure (CHF) mortality and hospitalisations in Quebec, Canada between 1990-1998 and compare trends in CHF mortality and morbidity with those in France. DESIGN: Population cohort study. SETTING: Province of Quebec, Canada. PATIENTS: Mortality data were obtained from the Quebec Death Certificate Registry and hospitalisation from the Quebec Med-Echo hospital discharge database. Cases with primary ICD-9 code 428 were considered cases of CHF. RESULTS: Monthly CHF mortality was higher in January, declined until September and then rose steadily (p<0.05). Hospital admissions for CHF declined from May until September (moving averages analysis p<0.0001). Seasonal mortality patterns observed in Quebec were similar to those observed in France. CONCLUSION: CHF mortality in Quebec is highest during the winter and declines in the summer, similar to observations in France and Scotland. This suggests that absolute temperatures may not necessarily be that important but increased CHF mortality is observed once environmental temperatures fall below a certain "threshold" temperature. Alternatively better internal heating and warmer clothing required for survival in Quebec may ameliorate mortality patterns despite colder external environments.     

Management of late-onset bleb leaks

PURPOSE OF REVIEW: This paper reviews various methods of both medical and surgical management of late bleb leaks. RECENT FINDINGS: The hood procedure without bleb removal may be preferred for small leaking blebs and autologous conjunctival bleb resurfacing for large leaking blebs. If hypotony is present preleak, revision of the underlying scleral flap may also be required. SUMMARY: Blebs with late leaks are a major problem after glaucoma filtration surgery and can result in hypotony or endophthalmitis. Conservative treatment and laser therapy both have limited success in sealing the leaks and are not as effective as surgical management. Many surgical techniques are used, but none is universally successful.     

Design, synthesis, and biological evaluation of thio-containing compounds with serum HDL-cholesterol-elevating properties

A novel series of substituted sulfanyldihydroimidazolones (1) that modulates high-density lipoprotein cholesterol (HDL-C) has been reported to have HDL-elevating properties in several animal models. Concerns about the chemical and metabolic stability of 1 directed us to explore the structure-activity relationship (SAR) of a related series of substituted thiohydantoins (2). Expansion of the scope of the thiohydantoin series led to exploration of compounds in related thio-containing ring systems 3-7 and the N-cyanoguanidine derivative 8. Compounds were tested sequentially in three animal models to assess their HDL-C elevating efficacy and safety profiles. Further evaluation of selected compounds in a dose-response paradigm culminated in the identification of compound 2.39 as a candidate compound for advanced preclinical studies.     

Hyperpigmentation: a review of common treatment options

Hyperpigmentation disorders are common and include a multitude of forms. They are typically divided into three large categories: dermal, epidermal, or mixed, depending on the site of abnormality. The location of the increased melanin affects treatment options, but therapy within a group is often similar. This paper discusses the treatment modalities, including topical and surgical approaches, available for the different types of hyperpigmentation.     

Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full-dose gemcitabine

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.     

Strong synergy between mutant ras and HPV16 E6/E7 in the development of primary tumors

E6/E7 oncogenes of high-risk human papilloma virus (HPV) subtypes are essential for the development of certain types of cancers. However, these oncogenes are insufficient to transform normal cells into an immortalized or malignant state. Mutant Ha-ras cooperates with E6/E7 of HPV subtype 16 in transformation of cells in vitro and may contribute to some HPV-associated cancers in humans. This study investigates whether HPV16 E6/E7 and v-Ha-ras synergize in vivo. FVB/n mice transgenic for v-Ha-ras gene (R+) were crossed with transgenic C57BL/6 mice that harbor E6/E7 of HPV16 (E+). Beginning at about 3 months of age, the bitransgenic E(+)R(+)(C57BL/6 x FVB/n) F1 mice developed mouth, eye and ear tumors. By 6 months, the prevalence of these types of mouth, eye and ear tumors was 100, 71 and 79% respectively in the E(+)R+ mice. Most tumors grew progressively until the mice had to be killed. The median times for the appearance of the first mouth, eye and ear tumor were 3.6, 4.3 and 4.2 months, respectively. For the two singly transgenic groups of mice, the prevalence of mouth, eye and ear tumors was 0, 0 and 6% (E(-)R+) and 0, 0 and 0% (E(+)R-), respectively, and the median time to first tumor was greater than 12 months for singly transgenic mice (E(-)R+, E(+)R-). Thus, a remarkable synergy occurred between the v-Ha-ras and HPV16 E6/E7 oncogenes in the development of primary tumors in mice.     

White coat effect in treated versus untreated hypertensive individuals: a case-control study using ambulatory and home blood pressure monitoring

BACKGROUND: Some studies have shown a significant white coat effect (WCE) (i.e., difference between clinic blood pressure [CBP] and awake ambulatory blood pressure [ABP]) to be present not only in untreated but also in treated hypertensive individuals. This study aims to assess 1) the prevalence and the magnitude of the WCE in treated versus untreated hypertensive persons, and 2) the usefulness of home blood pressure (HBP) versus ABP in the detection of this phenomenon. METHODS: A case-control study was conducted in 138 treated hypertensive patients and same number of sex- and age-matched untreated hypertensive subjects who had measurements of CBP (at least three visits), HBP, and ABP. Subjects with a WCE of >20/10 mm Hg (systolic/diastolic) were classified as clinic reactors. RESULTS: There was a trend for a larger WCE assessed by ABP monitoring in the untreated group (mean difference in systolic WCE, 1.8 +/- 22.2 mm Hg, 95% CI -2.0 to 5.5; diastolic 1.8 +/- 11.9 mm Hg, 95% CI -0.2 to 3.8) and for more untreated clinic reactors (27% untreated v 20% treated, odds ratio 1.5, 95% CI 0.9 to 2.7). The sensitivity, specificity, and positive and negative predictive values of HBP to detect clinic reactors correctly were 56%/62% (treated/untreated), 87%/84%, 52%/59%, and 89%/86%, respectively, with moderate agreement between HBP and ABP (kappa 0.42/0.46). CONCLUSIONS: In treated hypertensive patients, WCE seems to be reduced compared with that in untreated hypertensive persons but is not eliminated. In both untreated and treated hypertensive individuals HBP monitoring appears to be useful in the detection of the WCE, but it may not be appropriate as an alternative to the ABP method.