Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring.

BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard-of-care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. -0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes.

Effect of frequency on entrance and propagation pattern of high-frequency (radiofrequency) electrical currents in biologic tissues.

BACKGROUND: Radiofrequency electrical currents have a tendency to move toward the center of the bulk of biologic tissues. OBJECTIVES: To evaluate the effect of the frequency of currents on their entrance and propagation pattern in biologic tissues. MATERIALS AND METHODS: Three electrosurgical generators with 0.4, 1.5, and 3 MHz frequency outputs were studied. Current was applied using a metallic needle introduced into a piece of cow liver, with different amounts of energy delivered at multiple points. Cross-sections of the liver were then studied for tissue effect. The diameters of the coagulated areas at the deepest and most superficial parts were measured. The tendency of the currents for penetration in the deeper layers of tissue rather than in the superficial layers was assessed using the superficial diameter/deep diameter ratio. RESULTS: Diameter of coagulated area was larger around deeper parts than around superficial parts of the electrode. No correlation between frequency of current and the superficial/deep diameter ratio of the coagulation zone was found. CONCLUSION: Radiofrequency currents have a tendency to move toward the center of the tissue. Frequency of current over the range of 0.4-3 MHz did not show any effect on this tendency.

Risk of refracture associated with compliance and persistence with bisphosphonate therapy in Taiwan.

SUMMARY: Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. INTRODUCTION: Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. METHODS: This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). RESULTS: The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with <80 % compliance (p < 0.05). Nearly 50 % patients were noncompliant (MPR < 80 %) at 3 months, and only around 30 % patients were adherent at 1 year. Refracture risk increased with MPR < 80 %, age, and co-morbidities like diabetes mellitus or dementia. Patients with concomitant statin medication had significantly lower refracture risk. CONCLUSIONS: The compliance of Taiwanese patients with osteoporosis medication is poor, and refracture risk is related to compliance with bisphosphonate therapy.

Oncology in midlife and beyond.

The onset of the menopause is often a time when women's concerns can act as a powerful trigger to encourage healthy modifications in lifestyle which will maintain, or improve, their general health. This document aims to help women to understand their potential risks, to encourage them to find proactive preventive strategies by modifying some of their attitudes, and to use health resources (when available) to be screened. Cancer is an important cause of death but not the primary cause of mortality. Cardio/circulatory diseases represent 35-40% of causes of death in most developed countries and 20-25% of women will die from cancers in Western Europe, Australasia, high-income North America, high-income Asia Pacific, East Asia and Southern Latin America. Breast cancer, lung cancer and colorectal cancer are prevalent in most regions of the world. Cervical cancer remains a hallmark of low access to health care. Preventive strategies (decreasing smoking and alcohol consumption, losing weight, eating a healthy diet and undertaking physical activity) and implementation of screening could help to significantly decrease the incidence of and mortality from cancer. The mortality/incidence ratio is higher in developing countries compared to high-income regions as well as in subgroups of populations in developed countries with lower socioeconomic levels. Implementation of better diagnostic methods and management of cancer according to the local resources will help to decrease the mortality rate in developing countries, and effort has to be made to decrease social inequities and improve access to health care for low-income groups. In conclusion, cancer incidence is increasing as a consequence of longer life expectancy all over the world. National health programs are mandatory to implement screening and to improve individual management. Finally, educating women so that they are aware of ways to improve their general health, to minimize their own risk factors and to identify signs of change in their own health which may be markers of impending cancer will help to reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.

Evidence-based assessment of the impact of the WHI on women's health.

Following the announcement of the first results of the Women's Health Initiative (WHI) to the media in 2002, prior to their scientific publication, the resulting panic headlines had an immediate and lasting negative effect on use of menopausal hormone replacement therapy (HRT) around the world. Rates of use dropped by 40-80%. Symptomatic women then sought multiple alternative therapies but the majority of these have no greater effect than the effect seen from placebo in well-conducted trials of HRT. Some of these therapies have risks. Although anecdotally most menopause practitioners after 2002 can attest to having to counsel large numbers of women with debilitating menopausal symptoms who were too frightened to consider HRT, it is difficult to document loss of health-related quality of life in large population studies as they were not conducted. Similarly, the positive or negative effects of the marked decline in HRT on long-term morbidities and mortality have yet to be fully assessed. Recent studies have shown an increase in postmenopausal fractures and in some, but not all, populations a small temporary decline in breast cancer. Cardiovascular outcomes may not be apparent for another decade. Short-term, randomized, placebo-controlled trials confirm that HRT is the only therapy that effectively improves health-related quality of life in symptomatic women through a reduction in vasomotor and urogenital symptoms, joint pains and insomnia, while improving sexuality. The results of the re-analyses of the WHI data and new data from other studies do not justify the continuing negative attitude to HRT in symptomatic women who start HRT near menopause.

The assessment of efficacy of Diascorea alata for menopausal symptom treatment in Taiwanese women.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of Diascorea alata for treatment of menopausal symptoms. MATERIALS AND METHODS: Two-center, randomized, double-blind, placebo-controlled clinical investigation on 50 menopausal women randomly assigned to two groups, treated for 12 months with either placebo or two sachets daily of Diascorea extracts containing 12 mg/sachet. Primary outcome measures were changes in the Greene Climacteric Scale caused by Diascorea compared with placebo; secondary outcomes were changes in plasma hormone profiles. One-way ANCOVA test was performed to investigate the significance. RESULTS: At 6 months and at the end of treatment, those women who received Diascorea showed general improvement in almost all the clinical symptoms investigated. A significant reduction was noted in the total Greene scores in the Diascorea group assessed at the end of 12 months' treatment (p < 0.01). This phenomenon was more significant for the psychological parameters of anxiety than for other parameters. Apparent improvements were noted in the parameters 'feeling tense or nervous' (p = 0.007), 'insomnia' (p = 0.004), 'excitable' (p = 0.047) and 'musculoskeletal pain' (p = 0.019) among those receiving Diascorea. Diascorea consumption also resulted in positive effects on blood hormone profiles. CONCLUSIONS: Compared with placebo, Diascorea alata improves symptoms, particularly the psychological parameters in menopausal women. Safety monitoring indicated that standardized extracts of Diascorea alata were safe during daily administration over a period of 12 months.

Updated clinical recommendations for the use of tibolone in Asian women.

Tibolone, which is indicated for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women, has a tissue-specific mode of action different to that of conventional hormone replacement therapy (HRT). A large proportion of Asian postmenopausal women experience symptoms that most frequently include musculoskeletal pain, insomnia, forgetfulness, hot flushes and sexual dysfunction, and there is a need to address their specific requirements. Recent studies show that, in comparison to HRT, tibolone is as effective in alleviating menopausal symptoms and preventing bone loss, has a greater positive effect on sexual dysfunction and is associated with less vaginal bleeding, but it is rarely mentioned in guidelines for menopausal treatment. Levels of awareness amongst women about treatments for menopausal symptoms vary between Asian countries but, even in countries where awareness is high, HRT usage is much lower than in the West. To provide a practical approach to the use of tibolone in Asian postmenopausal women, a panel of experts in the management of menopause from 11 Asia Pacific countries has developed recommendations for its use, based on the evidence from clinical studies published since 2005. However, as much of the clinical data reviewed are from international studies, the recommendations and the treatment algorithm presented here are widely applicable.

Differential osmosensing signalling pathways and G-protein involvement in human cervical cells with different tumour potential.

Previous studies show that the regulatory volume decrease (RVD) in human cervical cells with different tumour potential may be mediated by different ion channels. The signalling events involved in regulating these channel activities are not clear. To screen the possible mechanisms involved in cell volume regulation in these cells, we examine intracellular mechanisms and second messengers listed as follows: phospholipase C (PLC), phospholipase A2 (PLA2), tyrosine kinase (TK), protein kinase C (PKC), protein kinase A (PKA), and cAMP. The involvement of G-protein was also studied. Our results showed that PLC signalling with downstream activation of PKC was involved in the cell volume regulation of cervical cancer cells. On the other hand, different PKC isoforms that were not related to upstream PLC regulation were involved in the RVD of human papillomavirus (HPV)-immortalised and normal cervical epithelia. Furthermore, GTP-gamma S facilitated the process of RVD in cervical cancer cells, while pertussis toxin retarded this process. In contrast, neither GTP-gamma S nor pertussis toxin showed effect on the RVD responses of HPV-immortalised and normal cervical cells.

Pituitary response to synthetic luteinizing hormone-releasing hormone in patients with Turner's syndrone.

Synthetic luteinizing hormone-releasing hormone (LHRH) was administered intravenously in a dose of 25 mug to 9 patients with Turner's syndrome of 45,XO karyotypes, 5 normal menstruating women, and 5 postmenopausal women. In patients with Turner's syndrome, the basal serum LH level was higher than that of the normal subjects and lower than that of postmenopausal women. The LH response to LHRH, when expressed as a percent of control, was comparable to that of the normal luteal phase and significantly higher than that of postmenopausal women. The basal FSH level was more elevated than the basal LH level. The FSH response to LHRH, when expressed as a percent of control, was similar to that of postmenopausal women and lower than that of normal subjects. The results suggest that pituitary function is preserved in patients with Turner's syndrome. I interpret the pituitary responsiveness and/or reserve of patients with Turner's syndrome as larger than that of postmenopausal women. A greater response of LH than of FSH to LHRH was observed in this study and is contrary to findings reported by others on teenage patients with Turner's syndrome. This suggests that the sensitivity of gonadotropins changes with age in Turner's syndrome.

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on cardiovascular risk factors.

OBJECTIVE: To determine the effects of oral and transdermal hormone replacement therapy on lipid profile and hemostatic factors in postmenopausal women. DESIGN: Twenty subjects were treated with oral E2 valerate (2 mg) combined with cyproterone acetate (1 mg) (group I) and 21 with transdermal E2 (1.5 mg) plus oral medroxyprogesterone acetate (5 mg) (group II). The effects on lipid profile and hemostatic parameters were evaluated at baseline and after 3, 6, and 12 months of treatment. RESULTS: Group I showed a stronger increase of high-density lipoprotein (HDL) cholesterol levels (2-8%) and stronger reduction of atherogenic indices (total cholesterol/HDL cholesterol and low-density lipoprotein/HDL cholesterol) than group II. Group II showed a more pronounced reduction of triglyceride (21-31%) and factor VII (6-10%) levels than group I. Both groups showed reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, and protein S, whereas protein C was increased after 12 months of treatment. CONCLUSIONS: The cardioprotective effects of hormone replacement therapy are demonstrated by favorable effects on lipid profile and fibrinolytic activity. Oral hormone replacement therapy showed a more prominent effect on lipoprotein metabolism than did transdermal administration, but transdermal medication had a stronger effect on triglyceride and coagulation factors. However, it needs to be considered that there is an increased risk of venous thrombotic events in the first year of treatment.

Transient hyperprolactinemia in infertile women with luteal phase deficiency.

This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Follicular phase treatment of luteal phase defect with follicle-stimulating hormone in infertile women.

Fifteen infertile women diagnosed by endometrial dating to have a luteal phase defect were treated with human pituitary follicle-stimulating hormone (hFSH) for 45 cycles. Human follicle-stimulating hormone was administered intramuscularly in a dose of 50 IU/day (group 1) for 35 cycles and 100 IU/day (group 2) for ten cycles from either the third or fifth day of the cycle for five days. Plasma estrogen was measured daily during drug injection. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation by basal body temperature during 11 pretreatment control cycles and 39 treatment cycles. Endometrial biopsies were performed on the seventh day after ovulation. The daily estrogen levels increased gradually during hFSH treatment. There was no significant difference between the two dosage groups. The mean progesterone levels were: 1) significantly (P less than .02) greater in the treatment cycles than in the control cycles, 2) significantly (P less than .05) greater in the pregnancy cycles than in the nonpregnancy cycles, 3) significantly (P less than .01) greater in the cycles with normal endometrial dating than in the cycles with abnormal endometrial dating after treatment, and 4) significantly (P less than .05) greater in group 1 than in group 2. After treatment, the endometrial biopsy specimens were improved to normal in 20 of 38 cycles. Five patients became pregnant during the treatment. The authors have concluded that hFSH may be useful in treatment of luteal phase defect.

Interference with uterine blood flow by clomiphene citrate in women with unexplained infertility.

OBJECTIVE: To investigate the effect of clomiphene citrate on the uterine blood flow in women with unexplained infertility. METHODS: Twenty-one women who had normal uterine blood flow (pulsatility index [PI] less than 3 from the LH peak to the middle luteal phase of a natural ovulatory cycle) were enrolled in this study. Patients were given clomiphene citrate (100 mg/day) from days 5-9 of the next ovulatory cycle. The PI values measured in the natural and clomiphene citrate-treated cycles were compared using repeated measures analysis of variance. Their correlations with the estradiol (E2) and progesterone concentrations in the treatment cycle were calculated using the Pearson correlation coefficient. RESULT: In the natural cycles of those with normal uterine blood flow, the highest impedance of uterine blood flow was detected at the late follicular phase, then blood flow increased during the luteal phase. In the clomiphene citrate-treated cycles, a statistically significant decrease in uterine blood flow also occurred during the early luteal phase (P < .05). No significant correlation of E2 or progesterone serum concentrations with PI values of the uterine artery could be found in either natural or clomiphene citrate-treated cycles. CONCLUSION: The use of clomiphene citrate decreases the uterine blood flow during the early luteal phase, a periimplantation stage.

Immunomodulation in women with endometriosis receiving GnRH agonist.

OBJECTIVE: To assess the changes in the subpopulations of lymphocytes and in lymphocyte mitogenic activity in women with endometriosis receiving GnRH-agonist treatment. METHODS: Twenty-six women with advanced endometriosis from the National Cheng Kung University Medical College were studied. Each received a total of six doses of GnRH agonist at 4-week intervals. Immunologic responses at various times after receiving GnRH-agonist treatment, including numbers of peripheral blood lymphocytes subsets and the lymphocyte proliferative activity, were analyzed using a repeated measures analysis of variance. Twenty-six healthy women who visited our gynecologic clinics for routine Papanicolaou smear examination at the time of the recruitment were enrolled as controls. The responses for each patient receiving GnRH agonist were normalized with respect to those of her matched control at each of the time points. The differences between post- and pretreatment data were estimated using generalized estimating equations. RESULTS: There was no significant difference in the sizes of lymphocyte subsets between patients and controls before treatment. After GnRH-agonist treatment, there was a trend in the rise of natural killer cell numbers early in the treatment period, with P values of .05 and .07 at 1-2 weeks and 2-3 weeks, respectively. This rise in natural killer cell numbers was not significant until 3-4 weeks and the second month after the treatment. There were no significant changes in the CD4+ and CD8+ T-cell subsets and B cells, although a slight increase in total T cells (ie, CD3+ T) was observed 1-2 weeks after receiving GnRH agonist. The T-cell mitogenic activities at the end of 2 and 4 months after GnRH-agonist treatment were 1.5 and 1.8 times, respectively, of those before treatment. CONCLUSION: The increase in natural killer cell numbers and the upregulation of T-lymphocyte mitogenic activity, which might be caused by a direct effect of GnRH agonist or a consequence resulting from the depression of estradiol by GnRH agonist, may have implications in the clinical treatment of endometriosis.

Use of synthetic luteinizing hormone-releasing hormone in induction of ovulation in amenorrheic patients.

Luteinizing hormone-releasing hormone (LH-RH), administered to normal women in divided intrramuscular doses or by intravenous infusion, resulted in a prolonged release of luteinizing hormone and follicle-stimulating hormone from the pituitary gland, reliably resulting in ovulation during the late follicular phase. LH-RH was administered 6 days after clomiphene to 18 amenorrheic, anovulatory, infertile women in whom clomiphene therapy had failed previously. When LH-RH was administered intramuscularly in two divided doses, ovulation occurred in six of eight women and in 11 of 22 woman-months of stimulation (50%). One pregnancy occurred. When LH-RH was administered by intravenous infusion, ovulation occurred in nine of ten women and in 16 of 26 woman-months of stimulation (61.5%); three of the ten women became pregnant. Pregnancy also followed treatment withLH-RH in one patient with irregular menses and functional sterility.

The induction of ovulation in amenorrheic patients with synthetic luteinizing hormone-releasing hormone: the significance of pituitary responsiveness.

The pituitary reserve of gonadotropins was evaluated with intravenous injections of 25 mug of synthetic luteinizing hormone-releasing hormone (LH-RH) in 32 patients with secondary amenorrhea. An obvious individual difference in the magnitude of the serum LH response was noted in these patients. Thus the patients were classified into four groups according to their pituitary responsiveness as expressed by the ratio of the serum LH stimulated peak to the basal level. Patients with values within the range of, or higher than, that of the normal follicular phase were classified as having high response (750% and above); within the range of that of the normal luteal phase as having moderate response (500 to 740%); between that of the normal luteal phase and that of postmenopausal women as having low response (250 to 490%); and within the range of, or lower than, that of postmenopausal women as having no response (240% and below). Among 26 clomiphene-failed patients in this series who were treated again with clomiphene and subsequent injection of LH-RH; 10 of 12 patients (25 or 35 cycles) with high response, 6 of 10 patients (12 of 28 cycles) with moderate response, and 1 of 4 patients (1 of 13 cycles) with low response ovulated. Five patients became pregnant. The results of this study indicate that in amenorrheic women the higher the pituitary response to LH-RH the greater the chance of inducing ovulation. Patients with secondary amenorrhea may thus be classified by assessing their pituitary response to LH-RH, which may be useful in predicting the chance for the successful induction of ovulation.

Paradoxical pituitary hormone responses in a case of primary hypothyroidism and Hashimoto's thyroiditis.

A 24-year-old woman is described with irregular menstruation, anovulation, and infertility due to primary hypothyroidism and Hashimoto's thyroiditis. Her baseline gonadotropins and thyroid-stimulating hormone (TSH) were increased. Microsomal and thyroglobulin antibodies were present. Stimulation of pituitary hormone release with thyrotropin-releasing hormone (TRH) resulted in appropriate responses of TSH and prolactin (PRL) as well as a substantial rise in the level of luteinizing hormone (LH). Luteinizing hormone releasing factor (LRF) markedly inhibited LH release. Bromoergocryptine led to inhibition of TSH and PRL. These results suggest that specific and nonspecific responses of pituitary glycoproteins to provocative stimuli reflect a profound disturbance of the hypothalamic-pituitary axis in this case of hypothyroidism.

Pregnancy induced with menotropins in a woman with polycystic ovaries, endometrial hyperplasia, and adenocarcinoma.

A 31-year-old woman is described with PCOD associated with endometrial hyperplasia and well-differentiated adenocarcinoma. Conservative treatment with ovulation induction was pursued for a total of 3 1/2 years. After CC treatment failed to achieve conception, treatment with menotropins resulted in a twin pregnancy that aborted spontaneously and a singleton term pregnancy. Hysterectomy was performed 4 1/2 years after the initial diagnosis of well-differentiated endometrial adenocarcinoma was made. Histologic examination of the endometrium showed no progression of the disease. Ovulation induction of patients with polycystic ovaries and well-differentiated and noninvasive endometrial adenocarcinoma may be justified in properly selected cases.