Long-term safety of an extended-cycle oral contraceptive (Seasonale): a 2-year multicenter open-label extension trial.

OBJECTIVE: The purpose of this study was to assess the long-term safety of Seasonale, 91-day extended-cycle oral contraceptive (OC). STUDY DESIGN: Following completion of a 1-year Phase 3 multicenter trial, patients from selected centers were invited to participate in this 2-year extension trial. In this open-label study all participants received the 91-day extended-regimen OC, Seasonale. RESULTS: There were 189 study participants enrolled from 27 sites. Patient exposure included 1130 completed 91-day cycles. Overall rates of study discontinuation and the incidence of adverse events were similar to the earlier Phase 3 clinical trial. Seasonale was well tolerated and the number of reported bleeding and/or spotting days reported diminished during the course of the study. CONCLUSION: This study confirms the findings from the previous clinical trial and demonstrates that Seasonale is a safe and effective therapy for long-term use.

A multicenter, randomized study of an extended cycle oral contraceptive.

OBJECTIVE: To assess the efficacy and safety of Seasonale, 91-day extended cycle oral contraceptive (OC). METHODS: A parallel, randomized, multicenter open-label, 1-year study of the OC Seasonale [30 microg ethinyl estradiol (EE)/150 microg levonorgestrel (LNG), and Nordette-28 (30 microg EE/150 microg LNG)] in sexually active, adult women (18-40 years) of childbearing potential. Patients received either four 91-day cycles of extended cycle regimen OC, or 13 cycles of the conventional 28-day OC with daily monitoring of compliance and bleeding via electronic diaries. RESULTS: When taken daily for 84 days followed by 7 days of placebo, the extended cycle regimen was effective in preventing pregnancy and had a safety profile that was comparable to that observed with the 28-day OC regimen that served as the control. While unscheduled (breakthrough) bleeding was reported among patients treated with the extended cycle regimen, it decreased with each successive cycle of therapy and was comparable to that reported by patients who received the conventional OC regimen by the fourth extended cycle. CONCLUSION: This study demonstrated that Seasonale, 91-day extended cycle OC containing 84 days of 30 microg EE/150 microg LNG followed by 7 days of placebo, was effective, safe and well tolerated.

A descriptive, correlational study of patient satisfaction, provider satisfaction, and provider workload at an army medical center.

Strong national interest in health care delivery systems and a highly competitive marketplace have mandated that military hospital commanders be increasingly aware of organizational performance. Historically, one variable that has been used to assess such performance is patient satisfaction with the care received. The purpose of this study was to measure patient satisfaction at a major military medical center and to assess how patient satisfaction correlated with the variables of provider satisfaction and nurse/patient ratio. One hundred eighty-eight patients completed the LaMonica-Oberst Patient Satisfaction Scale. Data analysis revealed that, although overall patient satisfaction was high, it was significantly higher on the intensive care units and in other areas where the nurse/patient ratio was high. Interestingly, there was no correlation between the staff's perceptions of their work environment and patient satisfaction. Findings from this study serve to highlight the continued need for a low nurse/patient ratio and are suggestive of the need for refinement of patient satisfaction survey tools available at present.

Nurse-physician communication: perceptions of nurses at an Army medical center.

The purposes of this study were to describe nurses' perceptions of their communication with physicians, as related to the openness of the communication, the accuracy of the information communicated, and the timeliness of the interaction; and further, to determine if specific demographic characteristics of nurses are associated with perceptions of positive communication. The sample (N = 112) consisted of professional nurses working on one of nine inpatient units at a major military medical center. Shortell's ICU Nurse-Physician Communication subscale was used to measure the nurses' perceptions of the degree to which openness, accuracy, and timeliness described their communication with physicians. Overall findings were that the nurses perceived a poor quality of communication between themselves and the physicians with whom they interacted. Results from this study further indicated that the perceived quality of nurse-physician communication was not related to a nurse's educational level, length of nursing experience, or length of time assigned to a specific unit. Finally, findings provided no evidence that perceived levels of nurse-physician communication were greater among permanent staff than temporary nursing staff, or in intensive care units versus general ward areas.

Evaluation and comparison of health care Work Environment Scale in military settings.

The purpose of this study was to describe health care providers' perceptions of their work environment at a large U.S. Army medical center, and to compare the findings to other military medical centers. The sample (N = 112) consisted of the professional nursing staff working on the nine inpatient units. The Work Environmental Scale (WES) was used to measure perceptions of the workplace relative to gender, position (head nurses, staff nurses, and agency nurses), specialty nursing (intensive care unit [ICU] versus non-ICU), education (MSN, BSN, and ADN), and patterns of differences between the WES subscales of four military medical centers. Results of the study indicate that there were no significant gender differences. Head nurses, non-ICU nurses, and MSN nurses perceived their environment more positively. There were significant differences in the WES subscales between the military hospitals. Implications for nursing using the WES were recommended.

Antiproliferative effects of low-dose micronized progesterone.

OBJECTIVE: To study the pharmacodynamic effects of oral micronized P on endometrial maturation. DESIGN: This was a controlled, open, parallel group, pilot study. SETTING: The experiment was performed in an outpatient academic clinical research unit. PATIENTS: Twelve healthy, P-challenged, estrogen-primed, postmenopausal women participated in the study. INTERVENTIONS: Patients were given 300 mg micronized P daily (8:00 A.M.) or twice (8:00 A.M. and 4:00 P.M.) daily from study days 1 through 14 after estrogen priming for 30 days. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after the 8:00 A.M. dose on study day 1 and 14 and again at 8:00 and 9:30 A.M. on days 3 and 5 fasting, days 7 and 9 after a fatty meal, and day 11 after a high fiber meal. Endometrial biopsies were taken on day 1 and 14. MAIN OUTCOME MEASURES: Progesterone concentrations were measured. Endometrial biopsies were studied for effects on histology, glycogen content of glands, ribosomal RNA, and nuclear estrogen receptors in glands, surface epithelium, and stroma. RESULTS: Day 1 and 14 P kinetics were similar for 8 hours. Dose-dependent increases in glandular glycogen, decrease in ribosomal RNA, and decrease in nuclear estrogen receptors were demonstrated. CONCLUSIONS: Oral micronized P can induce antiproliferative changes in the human endometrium at doses lower than those required for transformation of the endometrium to a full secretory state.

Utilization of supplemental agency nurses in an Army medical center.

The purpose of this study was to describe the perceived impact of supplemental agency nurses upon the quality of patient care, unit cohesiveness, and morale of permanently assigned personnel at an Army medical center. The study population consisted of 28 agency nurses and 138 permanently assigned nursing staff. The study was descriptive and exploratory in nature, utilizing the method of content analysis. Major themes that emerged from data analysis included economic, professional nursing, and patient care issues. Perceptions were that agency nurses provided the institution with necessary labor, but that the agency nurses had greater flexibility of hours and control over their practice. Permanently assigned nursing staff reported that the use of agency services hindered continuity of patient care, at times reduced the quality of care, negatively affected morale among personnel, and impacted adversely upon the time available for mission-related training.

Lea's Shield: a phase I postcoital study of a new contraceptive barrier device.

Lea's Shield is a new vaginal barrier contraceptive that may offer advantages over existing methods. It is made of silicone which is resistant to petroleum-based lubricants, does not absorb odors, and does not cause allergic reactions in users with latex sensitivity. It has an anterior loop for ease of insertion and removal and a one-way flutter valve. Its novel design has sufficient volume to fill the posterior fornix, which helps keep it in place and prevent sperm from entering the cervical os. This study evaluated with a standard postcoital test (PCT) the ability of the Lea's Shield used with spermicide or non-spermicidal lubricant to prevent sperm from entering midcycle cervical mucus. Ten sterilized women underwent four PCT cycles: one cycle in which no contraceptive barrier was used (a baseline cycle) and 3 cycles in which one of the following was used: Lea's Shield with spermicide, or with non-spermicidal lubricant, or the contraceptive diaphragm used with spermicide. All volunteers demonstrated more than 5 progressively motile sperm per high power field in the cervical mucus after intercourse in the baseline cycle. No motile sperm were found in the cervical mucus in any cycle in which Lea's Shield or the diaphragm was used with spermicide. No motile sperm were found in cervical mucus in 9 of 10 cycles in which Lea's Shield was used without spermicide. Only two progressively motile sperm were present in the cervical mucus of one volunteer who used the shield with non-spermicidal lubricant.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: The results of a Phase I postcoital study of Lea's Shield, a new vaginal barrier contraceptive, suggest that this device is as effective as the vaginal diaphragm, even when used without spermicide. Evaluated was the ability of the Lea's Shield to prevent sperm from entering midcycle cervical mucus. Ten sterilized women underwent a baseline cycle followed by three additional cycles under one of the following conditions: Lea's Shield with spermicide, Lea's Shield with a nonspermicidal lubricant, or standard vaginal diaphragm with spermicide. In the baseline cycle, all subjects demonstrated more than five progressively motile sperm per high power field in the cervical mucus after intercourse. No sperm were detected in the post-intercourse cervical mucus in either the women who used the standard diaphragm with spermicide or those using the Lea's Shield with spermicide. One volunteer who used the Lea's Shield without spermicide had two progressively motile sperm in the cervical mucus; however, this involved a small size device that is no longer manufactured and was considered unlikely to result in pregnancy. There were no side effects reported by Lea's Shield users. Advantages of this new device include its silicone composition (more resistant to heat and deterioration, less absorbent of odors, and less likely to cause allergic reactions than latex), anterior loop for ease of insertion and removal, one-way flutter valve, and lack of pressure on the urethra.

Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone.

OBJECTIVE: The pharmacokinetics of a 100 mg vaginal progesterone suppository was evaluated on days 1 and 7 and a 200 mg suppository on day 14. All the volunteers were given oral 17 beta-estradiol during the study. STUDY DESIGN: Ten postmenopausal women volunteered for this study. Progesterone was given as a vaginal suppository. Peripheral venous samples were obtained at appropriate intervals and analyzed for 17 beta-estradiol and progesterone levels. Area under the curve for progesterone was assessed by the trapezoidal method. Statistical analysis was performed by a one-way analysis of variance. RESULTS: Serum 17 beta-estradiol levels ranged from 22 to 182 pg/ml. Maximal serum progesterone levels ranged from 5.7 to 20.9 ng/ml, with the mean maximal levels 13.97, 16.09, and 12.68 ng/ml (not significantly different) and a mean area under the curve of 168.13, 207.64 and 227.71 ng/ml per hour on days 1, 7, and 14 (not statistically different). CONCLUSIONS: These data indicate that vaginal absorption of progesterone is efficient. The lack of difference in the area under the curve for both doses suggests that the vaginal mucosa or the total surface area of the vagina may limit the absorption of progesterone from the vagina.

Managed care at Eisenhower Army Medical Center: an initial experience.

Managed care is receiving a great deal of attention in the health care industry. In today's cost-conscious economic environment, managed care has been developed in an attempt to maximize quality of health care while minimizing the cost of providing that care. The purposes of this article are to (1) review the principles of clinical case management; (2) describe the implementation of clinical case management and critical paths at Dwight David Eisenhower Army Medical Center; (3) elaborate on successful strategies employed; and (4) address difficulties encountered. Finally, the study that is currently underway at the facility will be briefly discussed.

Indirect blood pressure measurement: a need to reassess.

BACKGROUND: Indirect blood pressure measurement is the assessment tool used most frequently in epidemiological studies and hypertension management in the population at large. OBJECTIVE: To review indirect blood pressure measurement within the context of nursing practice. RESULTS: Nurses are not following recommended American Heart Association measurement guidelines. CONCLUSION: A national program of certification in indirect blood pressure measurement, similar to that of basic and advanced cardiac life support, is needed. An initial approach to evaluating present practice is also suggested.

Study of hope in patients with critical burn injuries.

The purpose of this study was to determine which factors patients with critical burn injuries would identify as affecting their feelings of hope; specific attention was given to the influence of nursing actions on these feelings. The nonprobability purposive sample consisted of nine white male patients who had been admitted to a large burn center in the Southwest. Content analysis technique was used to determine the nursing behaviors that influenced the patients' levels of hope. Hope in this study is viewed as a dynamic process with past, present, and future dimensions. The majority of factors that subjects identified as affecting their levels of hope evolved from the present dimension. This study indicates that factors that affected each subject's level of hope were contingent upon where the patient was in the psychological recovery process that occurs after burn injury. Accordingly, the efficacy of specific nursing actions is contingent upon consideration of these same factors.

Tissue response to bioerodible, subcutaneous drug implants: a possible determinant of drug absorption kinetics.

The fibrous tissue compartments that develop in response to the subcutaneous implantation of bioerodible heat-fused rods of norethindrone and cholesterol (85 and 15%, respectively) were studied by light and electron microscopy at various intervals after implantation to determine whether the biological inflammatory response may play a role in drug absorption. Thirty-five regularly menstruating, sterilized (tubal ligation), healthy females each received four Annuelle rods. The microanatomy of seven of the largest implants (135 mg norethindrone) was studied. A dense fibrous biological compartment was found to surround each rod. By light microscopy no abnormal tissue response was revealed. Scanning and transmission electron microscopy showed that the surfaces of the rods were covered by a cellular matrix of mononuclear cells. The fibrous compartment was composed of a loose cellular bed immediately surrounding the norethindrone rod, a dense fibrous connective tissue envelope containing blood and lymphatic vessels, and an outer fatty connective tissue layer. Transmission electron microscopy confirmed that the cellular tissue immediately surrounding the rods was composed mainly of lipid laden macrophages. Norethindrone levels in tissue capsules at 3 and 10.5 months were 0.05 and 8.4% by weight, respectively. These observations suggest that the local inflammatory response plays a role in the active processing of this delivery system. This picture is qualitatively different from the general view of the fibrous capsule as a simple rate limiting membrane. The effects observed in this study suggest that a more complex, functional biological system develops in response to the subcutaneous introduction of a drug delivery device.

Selectivity and minimal androgenicity of norgestimate in monophasic and triphasic oral contraceptives.

The contraceptive progestin norgestimate (NGM) has a high affinity for uterine progestin receptors and a lack of affinity for androgen receptors similar to that of natural progesterone. NGM's selectivity results in excellent efficacy, cycle control, and minimal androgenicity when it is combined with ethinyl estradiol (EE). Clinical studies of a monophasic regimen of NGM/EE indicate a positive impact on lipid metabolism, revealing an increase in serum levels of high-density lipoprotein cholesterol with a concomitant and significant decrease in the low-density lipoprotein/high-density lipoprotein cholesterol ratio. Little impact on carbohydrate metabolism was noted. Serum levels of sex hormone binding globulin, an indicator of androgen-estrogen balance, also increased significantly with NGM/EE in accordance with its low androgenic activity. A significant between-regimen difference in SHBG was seen in a comparison study of NGM/EE and LNG/EE triphasic formulations (a mean rise of 68.6% with NGM/EE vs a decrease of 6.1% with LNG/EE). NGM's lack of estrogenicity was evidenced by unchanged prolactin levels and absence of effect on the coagulation system. In a large study of the monophasic formulation in 59,701 women, some improvement in acne was reported as well as minimal weight gain. An overview of clinical data is provided from United States and European trials as well as some preclinical data relevant to NGM's selectivity.

PIP: The contraceptive progestin norgestimate (NGM) has a high affinity for uterine progestin receptors and a lack of affinity for androgen receptors, similar to that of natural progesterone. NGM's selectivity results in excellent efficacy, cycle control, and minimal androgenicity when it is combined with ethinyl estradiol (EE). Clinical studies of a monophasic regimen of NGM/EE indicate a positive impact on lipid metabolism, revealing an increase in serum levels of high-density lipoprotein (HDL)-cholesterol with a concomitant and significant decrease in the low-density lipoprotein/HDL cholesterol ratio. Little impact on carbohydrate metabolism was noted. Serum levels of sex hormone binding globulin (SHBG), an indicator of androgen-estrogen balance, also increased significantly with NGM/EE in accordance with its low androgenic activity. A significant between-regimen difference in SHBG was seen in a comparison study of NGM/EE and levonorgestrel (LNG)/EE triphasic formulations (a mean increase of 68.6% with NGM/EE vs. a decrease of 6.1% with LNG/EE). NGM's lack of estrogenicity was seen through unchanged prolactin levels and an absence of effect on the coagulation system. In a large study of the monophasic formulation in 59,701 women, some improvements in acne were reported as well as in minimal weight gain. An overview of clinical data is provided from the US and European trials as well as some preclinical data relevant to NGM's selectivity.

Essentiality of a specific cellular terrain for growth of axons into a spinal cord lesion.

To date, there are no reports of growth of significant numbers of axons into or across a lesion of the mammalian spinal cord. However, recent studies showing that CNS axons will grow into PNS environments indicate that comparable growth into spinal cord lesions could be achieved if ischemic necrosis could be prevented and the lesion site repopulated by astrocytes and ependymal cells rather than by the macrophages, lymphocytes, and fibroblasts that generally accumulate at sites of CNS injury. To examine this possibility, we made a laminectomy at T5 in rats and crushed the spinal cord for 2 s with a smooth forceps (leaving the dura mater intact to prevent ingrowth of connective tissue). At 1 week, the lesion was filled with mononuclear cells, degenerating nerve fibers, and capillaries that were oriented parallel to the long axis of the spinal cord. By 2 weeks, longitudinally oriented cords of ependymal cells and astrocytes had migrated into the lesion from the adjacent spinal cord, and similarly oriented nerve fibers had begun to grow into the lesion along these capillaries and cellular cordons. The mononuclear cells had now assumed phagocytic activity and were engorged with myelin and other cellular debris. After 3 weeks, the astrocytes had elaborated thick cell processes. The nerve fibers in the lesion were still oriented longitudinally but had increased in number and were often arranged in small fascicles. These observations provide the first histological evidence of growth of nerve fibers into a lesion of the rat spinal cord. We conclude that the intrinsic regenerative capacity of the spinal cord can be expressed if ischemic necrosis and collagenous scarring are prevented and the spinal cord parenchyma is first reconstructed by its nonneuronal constituents.