Screening for tuberculosis: the port of arrival scheme compared with screening in general practice and the homeless.

BACKGROUND: Tuberculosis is increasing in London, especially in those recently entering the UK from an area of high incidence. Screening through the port of arrival scheme has a poor yield and has been considered discriminatory. METHODS: A study was undertaken to compare the yield and costs of screening new entrants in a hospital based new entrants' clinic (1262 referrals from the port of arrival), general practice (1311 new registrations), and centres for the homeless (267 individuals) using a symptom questionnaire and tuberculin testing if indicated. Clinical outcome measures were cases of tuberculosis, tuberculin reactors requiring chemoprophylaxis and BCG vaccinations. Cost outcomes were cost per individual screened and cost per individual per case of tuberculosis prevented. RESULTS: Verbal screening limited tuberculin testing to 16% of those in general practice; most were tested at the other two locations. Intervention (BCG vaccination, chemoprophylaxis or treatment) occurred in 27% of those who received tuberculin testing. Attendance for screening was 17% of the port of arrival notifications (63% had registered with a GP), 54% in primary care, and 67% in the homeless (42% registered with a GP). Costs for screening an individual in general practice, hostels for the homeless, and the new entrants' clinic were 1.26 pounds sterling, 13.17 pounds sterling and 96.36 pounds sterling, respectively, while the cost per person screened per case of tuberculosis prevented was 6.32 pounds sterling, 23.00 pounds sterling, and 10.00 pounds sterling, respectively. The benefit of screening was highly sensitive to the number of cases of tuberculosis identified and case holding during treatment. CONCLUSION: Screening for tuberculosis in primary care is feasible and could replace hospital screening of new arrivals for those registered with a GP.

"Estrophasic" dosing: A new concept in oral contraceptive therapy.

The first of a new "estrophasic" type of oral contraceptive with 20 microg ethinyl estradiol on cycle days 1 through 5, 30 microg ethinyl estradiol on days 6 through 12, and 35 microg ethinyl estradiol on days 13 through 21 and 1 mg norethindrone acetate throughout the cycle (Estrostep; Parke-Davis, Morris Plains, NJ) combines a continuous low progestin dose with a low, gradually increasing estrogen dose. It was developed to ensure good cycle control while conferring the benefits of low hormone content, such as minimizing estrogen-related side effects. In a double-blind, randomized, parallel-group trial, Estrostep provided acceptable cycle control and excellent tolerableness, comparable to that of the 30-microg ethinyl estradiol monophasic control drug. In a second study Estrostep demonstrated a neutral impact on serum lipids, like the triphasic control drug. This new oral contraceptive design offers a useful low-dose alternative to existing combination preparations.

Histologic classification and pathologic findings for endometrial biopsy specimens obtained from 2964 perimenopausal and postmenopausal women undergoing screening for continuous hormones as replacement therapy (CHART 2 Study).

OBJECTIVE: The aim of this study was to screen for disorders and to histologically classify endometrial biopsy specimens from 2964 perimenopausal and postmenopausal women who were candidates for hormonal replacement therapy. STUDY DESIGN: Endometrial biopsy specimens were obtained with a Vabra aspiration curette, processed by standard methods, and stained by hematoxylin and eosin and special methods to reveal subtle features of the endometrium. RESULTS: Of the endometrial biopsy specimens, 68.7% were atrophic, 23.5% were proliferative, 0.5% were secretory, 0.6% were hyperplastic, 0.07% were adenocarcinoma, and 6.6% were insufficient for classification. Three independent senior microscopists agreed on the classification of each biopsy specimen. CONCLUSION: The number of patients is the largest ever screened for a single hormone replacement therapy study. The low yield of endometrial cancer indicates that biopsies are unnecessary before hormone replacement therapy is initiated in asymptomatic women.

Effects of regular and extended-release gemfibrozil on plasma lipoproteins and apolipoproteins in hypercholesterolemic patients with decreased HDL cholesterol levels.

We have studied, in a prospective blinded fashion, the effects of regular and extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo) levels in hypercholesterolemic subjects with decreased high density lipoprotein (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80 years of age with baseline plasma low density lipoprotein (LDL) C levels > or = 4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and triglyceride levels < or = 3.4 mmol/L (300 mg/dl). All subjects were stabilized on a diet for eight weeks prior to entry into two different protocols. In the first protocol 229 subjects were randomized to placebo or extended-release gemfibrozil (1200 mg/day) for 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) for 6 months (equivalency trial). Changes in lipids and apos were stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both studies, treatment with gemfibrozil, either regular or extended-release, was associated with significant (P < 0.05) decreases in plasma very low density lipoprotein (VLDL) C and triglyceride levels of 42-45% and 33-37%, respectively, in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%, respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions from baseline in directly measured LDL-C levels were observed in both groups (3-6% and 8-9%, respectively). These reductions were less than those observed for calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased by 15-16%, 5-6%, and 21-25%, respectively, in patients with HDL-C < 0.9 mmol/l, and by 6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l. These differences in HDL-C levels reached statistical significance in the equivalency trial (P < 0.0001) and were independent of baseline triglyceride levels. Our data indicate that gemfibrozil, either regular or extended-release, is highly effective in lowering plasma triglyceride levels and increases HDL-C levels by approximately 15% in hypercholesterolemic patients with low HDL-C levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than triglyceride, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. This agent also raises apo A-II levels much more than apo A-I levels.

Efficacy and local tolerance of a low-dose, 7-day matrix estradiol transdermal system in the treatment of menopausal vasomotor symptoms.

OBJECTIVE: To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17 beta-estradiol (E2) daily for 7 days for the relief of vasomotor symptoms. METHODS: A total of 324 surgically or naturally menopausal women, all with prior hysterectomy and moderate to severe vasomotor symptoms (56-140 hot flushes per week, with episodes of sweating, during a baseline observation period), participated in two independent, 12-week, randomized, double-blind, placebo-controlled studies. After a 4-week, treatment-free period, each woman received a continuous regimen of either one E2 transdermal system, two E2 transdermal systems, or placebo transdermal system(s) applied every week for 12 weeks. Efficacy was measured as reduction in hot flush frequency, determined from subject diaries. To measure local tolerance, skin irritation (erythema and edema) was objectively and systematically evaluated under blue light after removal of the transdermal system(s). Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1, 9, 30, 58, 79, and 84. RESULTS: Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week (84% decrease) after 12 weeks of transdermal E2 treatment. Compared with placebo, the decrease in hot flush frequency was significant as early as weeks 2 and 3, and was maintained through the end of the study. Few clinically significant skin reactions occurred, and only nine (3%) of the subjects withdrew because of a skin effect. After initial increase, serum E2 concentrations remained stable throughout the study, achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems, respectively. CONCLUSION: The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therapy and was very well tolerated. The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens, but at lower serum E2 concentrations. This result may be due to the stable E2 blood level achieved with this transdermal system.