Pooled analysis of sustained response rates for extended release quetiapine fumarate as monotherapy or adjunct to antidepressant therapy in patients with major depressive disorder

Background

Clinical trials are not generally powered to analyze outcomes such as sustained response. We evaluated sustained response rates for patients with major depressive disorder receiving quetiapine XR as monotherapy or adjunct therapy.

Method

Post hoc analyses of pooled data from four previously reported randomized, placebo-controlled studies of quetiapine XR 150 and 300 mg/day as monotherapy or adjunct therapy to ongoing antidepressant. Sustained response rates (≥50% reduction in MADRS total score at specific timepoint and each subsequent visit until Week 6) were calculated at Weeks 1, 2, and 4; rates were compared using a Cochran–Mantel–Haenszel analysis.

Results

In the monotherapy studies, the proportion of patients experiencing sustained response was greater with quetiapine XR 150 mg/day versus placebo at Week 2 (20.0% vs. 13.3%; p<0.05) and Week 4 (33.3% vs. 23.3%; p<0.01) (observed cases [OC]). The corresponding sustained response rates for quetiapine XR 300 mg/day were 18.0% (p=0.104) and 29.7% (p=0.063), respectively (OC).The proportion of patients experiencing sustained response was greater in the adjunct studies versus placebo at Weeks 2 and 4 for quetiapine XR 150 (Week 2, 30.1% vs. 15.2%, p<0.001; Week 4, 40.1% vs. 32.0%, p<0.05) and 300 mg/day (Week 2, 29.0% vs. 15.2%, p<0.001; Week 4, 42.0% vs. 32.0%, p<0.05) (OC).

Limitations

Post hoc analyses, acute treatment period; no active comparator.

Conclusions

Quetiapine XR as monotherapy (150 mg/day at Weeks 2 and 4) or adjunct to ongoing antidepressant therapy (150 and 300 mg/day at Weeks 2 and 4) increased sustained response rates versus placebo.     

Effect of raloxifene and low-dose percutaneous 17β-estradiol on menopause symptoms and endometrium—A randomized controlled trial

Objective

To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17β-estradiol associated with raloxifene in postmenopausal women.

Design

randomized placebo-controlled study.

Method

Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n = 20), 0.5 mg percutaneous 17β-estradiol associated to 60 mg raloxifene (RLX + E₂; n = 16) or placebo (PLC; n = 16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study.

Results

At baseline, the mean Kupperman index was 23.7 ± 1.8 in RLX group, 22.9 ± 1.9 in RLX + E₂ group and 22.6 ± 1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX + E₂ and placebo were significantly superior to RLX in reducing hot flush severity (p < 0.05). Endometrial thickness did not change in both groups. The association of percutaneous low-dose 17β-estradiol to raloxifene was not associated with proliferation of endometrium neither in hysteroscopies nor in endometrial biopsies at the third month of treatment. No vaginal bleeding was reported during the study.

Conclusions

The association of percutaneous low dose of 17β-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.     

Treatment for premenstrual syndrome with Vitex agnus castus: A prospective,randomized, multi-center placebo controlled study in China

Objectives

To investigate the efficacy and safety of VAC BNO 1095 extract in Chinese women suffering from moderate to severe premenstrual syndrome (PMS).

Methods

Prospective, double-blind, placebo controlled, parallel-group, multi-center clinical trial design was employed. After screening and preparation phase lasting three cycles, Eligible patients were randomly assigned into treatment or placebo groups and had treatment with VAC extract or placebo for up to three cycles. Efficacy was assessed using the Chinese version PMS-diary (PMSD) and PMTS.

Results

Two hundred and seventeen women were eligible to enter the treatment phase (TP) and were randomly assigned into the treatment group (108) or the placebo group (109), 208 provided the efficacy data (treatment 104, placebo 104), and 202 completed the treatment phase (treatment 101, placebo 101). The mean total PMSD score decreased from 29.23 at baseline (0 cycle) to 6.41 at the termination (3rd cycle) for the treatment group and from 28.14 at baseline (0 cycle) to 12.64 at the termination (3rd cycle) for the placebo group. The total PMSD score of 3rd cycle was significantly lower than the baseline in both groups (p < 0.0001). The difference in the mean scores from the baseline to the 3rd cycle in the treatment group (22.71 ± 10.33) was significantly lower than the difference in the placebo group (15.50 ± 12.94, p < 0.0001). Results of PMTS were similar, the total scores for PMTS were significantly lower between the two groups (p < 0.01) and within each group (p < 0.01). The score was decreased from 26.17 ± 4.79 to 9.92 ± 9.01 for the treatment group, and from 27.10 ± 4.76 to 14.59 ± 10.69 for the placebo group. A placebo effect of 50% was found in the present study. No serious adverse event (SAE) occurred in both groups.

Conclusion

Vitex agnus castus (VAC BNO 1095 corresponding to 40 mg herbal drug) is a safe, well tolerated and effective drug of the treatment for Chinese women with the moderate to severe PMS.     

Genetic associations with acute stress-related changes in eating in the absence of hunger

Background

Acute psychological stress is associated with eating in the absence of hunger.

Objective

To investigate if BclI and FTO polymorphisms are associated with eating in the absence of hunger as a result of acute psychological stress.

Methods

FTO (rs9939609) and BclI were genotyped in 98 subjects (BMI = 23.9 ± 3.3 kg/m²). In a randomized crossover design, the ‘eating in absence of hunger’ protocol was measured as a function of acute stress vs. a control task and of STAI (State Trait Anxiety Index) state scores.

Results

In comparison with the FTO T allele, the A allele was associated with an increased feelings of hunger after food intake in the stress (11 ± 10 vs. 18 ± 15, p < 0.01) and control condition (12 ± 9 vs. 16 ± 12, p < 0.05), even though food intake was not different. For the first time, it was observed that in comparison to the BclI C/C genotype, the BclI G/G genotype was associated with higher STAI states scores at 0, 10, and 20 min after the stress condition (30.8 ± 6.4 vs. 36.3 ± 8.2; 28.3 ± 5.5 vs. 32.3 ± 7.5; 27.7 ± 6.1 vs. 31.2 ± 7.5, p < 0.05). Additionally, the BclI G/G genotype was associated with a larger difference in energy intake between the stress and control condition, in comparison with the BclI C/C genotype (136.6 ± 220.4 vs. 29.4 ± 176.3 kJ, p < 0.04).

Conclusion

In concordance with previous studies, the FTO A allele is related to a lower feeling of hunger after a standardized meal. For the first time, the BclI G/G genotype is shown to be associated with increased sensitivity to psychological stress, and increased eating in the absence of hunger after stress.

Practice implications

Interventions to reduce body weight should consider the subjects’ genetic background.     

A 12-month randomized controlled trial of balance training in elderly women with osteoporosis: Improvement of quality of life

Objective

Physical and psychological incapacity, including fear of falling is related to decreased satisfaction with life in osteoporosis (OP). The impact of a balance exercise program on improving the quality of life is not well established. We have, therefore, investigated the effect of 12-month Balance Training Program in quality of life, functional balance and falls in elderly OP women.

Methods

Sixty consecutive women with senile OP were randomized into a Balance Training Group (BT) of 30 patients and no intervention control group (CG) of 30 patients. The BT program included techniques to improve balance over a period of 12 months (1 h exercise session/week and home-based exercises). The quality of life was evaluated before and at the end of the trial using the Osteoporosis Assessment Questionnaire (OPAQ), functional balance was evaluated by Berg Balance Scale (BBS). Falls in the preceding year were noted and compared to the period of study.

Results

The comparison of OPAQ variations (INITIAL–FINAL) revealed a significant improvement in quality of life in all parameters for BT compared to CG: well-being (1.61 ± 1.44 vs. −1.46 ± 1.32, p < 0001), physical function (1.30 ± 1.33 vs. −0.36 ± 0.82, p < 0.001), psychological status (1.58 ± 1.36 vs. −1.02 ± 0.83, p < 0.001), symptoms (2.76 ± 1.96 vs. −0.63 ± 0.87, p < 0.001), social interaction (1.01 ± 1.51 vs. 0.35 ± 1.08, p < 0.001). Of note, this overall benefit was paralleled by an improvement of BBS (−5.5 ± 5.67 vs. +0.5 ± 4.88 p < 0.001) and a reduction of falls in 50% in BT group vs. 26.6% for the CG (RR: 1.88, p < 0.025).

Conclusion

The long-term Balance Training Program of OP women provides a striking overall health quality of life improvement in parallel with improving functional balance and reduced falls.     

Psychological insulin resistance in geriatric patients with diabetes mellitus

Objective

To determine the extent to which geriatric patients with diabetes mellitus experience psychological insulin resistance (PIR).

Methods

A total of 67 unselected geriatric patients with diabetes (mean age 82.8 ± 6.7 years, diabetes duration 12.2 [0.04–47.2] years, 70.1% female) were recruited in a geriatric care center of a university hospital.A comprehensive geriatric assessment (CGA) was performed including WHO-5, Hospital Anxiety and Depression Scale (HADS), Mini Mental State Examination (MMSE) and Barthel-Index. We assessed PIR using the Barriers of Insulin Treatment Questionnaire (BIT) and the Insulin Treatment Appraisal Scale in a face-to-face interview.

Results

Insulin-naïve patients (INP) showed higher PIR scores than patients already on insulin therapy (BIT-sum score: 4.3 ± 1.4 vs. 3.2 ± 1.0; p < 0.001). INP reported in the BIT increased fear of injection and self-testing (2.4 ± 2.4 vs. 1.3 ± 0.8; p = 0.016), expect disadvantages from insulin treatment (2.7 ± 1.6 vs. 1.9 ± 1.4; p = 0.04), and fear of stigmatization by insulin injection (5.2 ± 2.3 vs. 3.6 ± 2.6; p = 0.008). Fear of hypoglycemia, however, did not differ significantly (6.3 ± 2.8 vs. 5.1 ± 3.1; p = 0.11). Depression was not shown to be a barrier to insulin therapy.

Conclusion

INP with diabetes have a significantly more negative attitude toward insulin therapy in comparison to patients already on insulin.

Practice implications

Systematic assessment of barriers of insulin therapy, individualized diabetes treatment plans and information of patients may help to overcome such negative attitudes, leading to quicker initiation of therapy, improved adherence to treatment and a better quality of life.     

The change of insulin levels after six weeks antidepressant use in drug-naïve major depressive patients

Background

A reciprocal relationship between diabetes risk and depression has been reported. There are few studies investigating glucose–insulin homeostasis before and after short-term antidepressant treatment in drug-naïve major depressive disorder (MDD) patients.

Methods

This study included 104 healthy controls and 50 drug-naïve MDD patients diagnosed according to the DSM-IV criteria. These MDD patients were randomly assigned to receive fluoxetine or venlafaxine for six weeks. Depressive symptoms, body mass index, fasting plasma levels of glucose and insulin were measured.

Results

Compared to the healthy controls, the fasting plasma insulin and the homeostasis model of assessment for pancreatic β-cell secretory function (HOMA-β) was significantly lower in the MDD patients before antidepressant treatment (7.7±4.8 μIU/mL vs. 5.1±4.2 μIU/mL, p=0.006; 114.2±72.3% vs. 74.8±52.0%, p=0.005, respectively). However, these indices were not correlated with depression severity. After 6 weeks of fluoxetine or venlafaxine treatment, the level of HOMA-β borderline significantly increased (108.1±75.5%, p=0.059).

Limitations

The study was limited by the follow-up duration and lack of a placebo group.

Conclusions

Antidepressants might affect insulin secretion independently of the therapeutic effects on MDD. Further studies are needed to investigate the long-term effects of antidepressants on insulin regulation in MDD patients.     

Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen

Introduction

Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the ‘grey zone’.

Objective

To examine the predictive value of sialic acid in prostate neoplasms.

Study design

In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy.

Results

The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06 ± 10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086 ± 8.7 mg/dl) (p < 0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy.

Conclusion

Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.     

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

Effects of continuous combined hormone replacement therapy and clodronate on bone mineral density in osteoporotic postmenopausal women: A 5-year follow-up

Objective

To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers.

Design

Prospective, partly randomized trial.

Setting

Kuopio University Hospital, Finland.

Population

167 osteoporotic women (61 ± 2.7 years; T-score ≤ −2.5 SD).

Methods

Estradiol 2 mg + NETA 1 mg, randomization to additional 800 mg clodronate (n = 55, HT + C-group) or placebo (n = 55, HT-group); if contraindications to HRT, clodronate (n = 57, C-group).

Main outcome measures

BMD by DXA after 1, 3 and 5 years, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) at the baseline and after 3 years.

Results

After 5 years, adjusted lumbar BMD increased by 4.2% in the HT-group and 3.7% in the HT + C-group. The C-group showed a decrease of −1.1%, the total difference being 5.3% and 4.8% between HT, HT + C vs. C-group, respectively (p < 0.001). In the femoral neck, the adjusted 5-year BMD benefit was 1.3% and 2.4% in the HT- and HT + C-groups, respectively, the net loss of BMD in the C-group was −3.3% (p < 0.05 between HT + C vs. C). By 3 years, OC decreased by 55.0%, 70.3% and 53.8% in the HT-, HT + C- and C-groups, respectively (p < 0.001 vs. baseline). The significant decreases of BAP were 39.4% in the HT-group, 42.1% in the HT + C-group and 30.2% in the C-group with no significant differences between the groups after adjustments.

Conclusions

In postmenopausal women with osteoporosis, HRT increased spinal and femoral BMD, but the combination of HRT and clodronate did not offer an extra gain of bone mass.     

Efficacy of soy isoflavones for depressive symptoms of the climacteric syndrome

Objectives

To evaluate the efficacy of soy isoflavones extract (SIE) in the treatment of depressive symptoms in women with climacteric syndrome.

Methods

Placebo-controlled double-blind randomized study with 84 climacteric outpatients attended in the Lauro Wanderley University Hospital in Joao Pessoa (PB), Brazil. In the assessment of the depressive symptoms, the Brazilian version of the Center of Epidemiologic Studies of Depression (CES-D) scale was used, on the pre-treatment visits (VT1), 8th (VT2) and 16th (VT3) weeks after treatment. The experimental group (EG) received the daily dose of 120 mg SIE and the control group (CG), placebo. The primary efficacy measure was the comparison of the percent reductions in the CES-D scores from VT1 to VT3 between EG and CG (t-test, p < 0.05). The security analysis consisted of laboratory and clinical evaluation of adverse events.

Results

The CES-D scores in the EG reduced from 12.5 (±4.2) in VT1 to 9.9 (±3.6) in VT2 (VT2 < VT1, p = 0.001) and 8.2 (±3.8) in VT3 (VT3 < VT2, p = 0.007), while the CG, reduced from 13.0 (±4.8) in VT1 to 10.1 (±4.1) in VT2 (VT2 < VT1, p = 0.001) and 9.4 (±4.1) in VT3 (VT2 = VT3, p > 0.05). In the outcome of the 16-week treatment (VT1–VT3), reduction of the CES-D scores did not reach statistical significance between groups. There were no clinically relevant adverse events attributable to the treatment.

Conclusions

The treatment with soy isoflavones did not produce significant reduction on the depressive symptoms of a predominantly affective nature evaluated in this study. The symptomatic reduction initially observed was apparently a nonspecific response to treatment, corroborating evidences from the literature on the placebo phenomenon in treatment of the climacteric syndrome.     

Serum cathepsin K as a marker of bone metabolism in postmenopausal women treated with alendronate

Context

Cathepsin K is a member of the cysteine protease family that cleaves both helical and telopeptide regions of collagen I, the major type of collagen in bone. Measurement of circulating levels of cathepsin K may be useful to assay the number or function of osteoclasts.

Objective

The aim of the study was to evaluate the role of serum cathepsin K as a biochemical marker of bone metabolism in patients with postmenopausal osteoporosis before and after treatment with alendronate.

Design, setting and participants

The study was a case–control and prospective study with postmenopausal osteoporotic women including a total number of 86 subjects. Serum cathepsin K was determined in 46 women with postmenopausal osteoporosis before and after 3, 6 and 12 months of treatment with alendronate. Basal serum cathepsin K levels were also compared between premenopausal healthy women (n = 20), postmenopausal women without osteoporosis (n = 20) and osteoporotic women. In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) were measured.

Main outcome measure

Changes in cathepsin K serum levels after alendronate treatment.

Results

Serum cathepsin K levels were higher in postmenopausal women with osteoporosis (9.4 ± 11 pmol/L) compared with healthy postmenopausal women (6.8 ± 8.1 pmol/L; p < 0.01) and premenopausal women (6.3 ± 5.0 pmol/L, p < 0.01). Serum cathepsin K decreases gradually after alendronate treatment (17% at 3 months, 22% at 6 months and 41% at 12 months, p < 0.01). In contrast, the treatment resulted in early and sustained reductions in serum CTX.

Conclusion

We conclude that serum cathepsin K seems to provide additional information on bone metabolism in postmenopausal women treated with alendronate.     

Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: Results from a double-blind,controlled study

Objectives

Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women. The primary aim of this double-blind, multi-centre, randomised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone.

Study design

313 women with ≥50 moderate to severe hot flushes during the previous week were randomised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone (E 0.5 mg/D 2.5 mg), 1 mg 17β-oestradiol/5 mg dydrogesterone (E 1 mg/D 5 mg) or placebo for 13 weeks. The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks, whilst the other groups continued on the same treatment.

Results

After 13 weeks, the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group (−6.4 vs. −4.9, p < 0.001) and comparable to that in the 1/5 mg group (−6.3). E 0.5 mg/D 2.5 mg and E 1 mg/D 5 mg significantly improved the total Menopause Rating Scale score. The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg. The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81%; this increased to 91% in months 10–12.

Conclusions

Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life, and was associated with a high amenorrhoea rate and a good tolerability profile.     

The effect of hormone therapy on serum melatonin concentrations in premenopausal and postmenopausal women: A randomized,double-blind,placebo-controlled study

Objectives

Melatonin levels decrease physiologically with age, and possibly with the transition to menopause. The plausible influence of hormone therapy (HT) on melatonin is poorly understood. The aim of this randomized, placebo-controlled, double-blind trial was to investigate the effect of HT administration on serum melatonin concentrations in late premenopausal and postmenopausal women.

Study design

Analyses were carried out among 17 late premenopausal and 18 postmenopausal healthy women who participated in a prospective HT study in Finland. Serum melatonin was sampled at 20-min (21:00–24:00 h; 06:00–09:00 h) and 1-h (24:00–06:00 h) intervals at baseline and after 6 months with HT or placebo.

Main outcome measures

Melatonin levels and secretion profile after 6 months of HT compared to placebo.

Results

Mean melatonin levels, mean melatonin exposure level (area under curve, AUC) and mean duration of melatonin secretion did not differ after 6 months with HT vs. placebo, irrespectively of the reproductive state. However, in postmenopausal women the melatonin peak time (acrophase) was delayed by 2.4 h (2 h 21 min) on average after 6 months with HT vs. placebo (p < 0.05). No interaction between time and group was detected when melatonin level was modelled before or after treatment.

Conclusions

Administration of HT to postmenopausal women alters melatonin peak time, but not melatonin levels. Further research on larger clinical samples is needed to better understand the effects of HT on melatonin profile.     

The variant of CD11b,rs1143679 within ITGAM, is associated with systemic lupus erythematosus and clinical manifestations in Brazilian patients

Background/aims

Immune responses mediated by complement receptors (CR) are impaired in patients with systemic lupus erythematosus (SLE). Regarding CR3 (CD11b/CD18), the CD11b subunit is encoded by the ITGAM gene and a single nucleotide polymorphism (G230A; rs1143679) in ITGAM changes an arginine to a histidine at position 77 (R77H). We assessed whether the variant R77H, rs1143679 within ITGAM, is associated with the risk to developing SLE and the clinical manifestations of Brazilian SLE patients.

Methods

The rs1143679 was genotyped by SSP-PCR in 157 patients with SLE and 147 healthy individuals. Clinical and laboratorial manifestations were obtained from the official medical records according the criteria of the American College of Rheumatology.

Results

The 77H variant was associated with susceptibility to SLE (OR = 1.8); the frequencies of the minor allele A were 0.25 (SLE) and 0.15 (healthy) (p < 0.01). In addition, the minor allele A was associated with lupus nephritis (p = 0.02) and antiphospholipid antibodies (p = 0.04).

Conclusion

These results showed that the rs1143679 variant is also associated with the risk to SLE in our population and with the risk to specific clinical manifestations, as nephritis and presence of antiphospholipid antibodies. These results may have implications for discussing the association of this polymorphism with the IC deposition in SLE.     

Increased Toll-like receptor 9 expression by B cells from inflammatory bowel disease patients

Background

Toll-like receptors (TLRs) are important mediators of the innate immune response. Our aim was to evaluate TLR9 expression in peripheral B cells, taken from inflammatory bowel disease (IBD) patients before and after anti-inflammatory treatment. Nineteen patients with IBD (12-crohn’s disease, 7-ulcerative colitis) and 18 healthy controls were included in the study. Disease severity was assessed using the Pediatric/Adults crohn’s disease activity index and the ulcerative colitis activity index as needed. Accordingly, patients were classified as mild, moderate or severe disease. Peripheral B cells isolated from IBD patients, before and after anti-inflammatory treatment, and from the control group, were cultured for 24 h with and without CpG oligodeoxynucleotides (ODN-CpG) 0.5 μM. TLR9 expression by memory B cells (CD19+CD27+) was assessed by flow cytometry.

Results

We found that TLR9 expression by peripheral B cells was significantly higher in IBD patients than that in healthy controls (12.42 ± 9.5 MFI vs. 6.0 ± 2.6 MFI p = 0.02). The addition of ODN-CpG to B cells resulted in a significantly increase of TLR9 expression in B cells from healthy controls (6.5 ± 3.2 MFI vs. 8.8 ± 4.2 MFI p = 0.007). On the contrary, B cells from IBD patients only partly respond to the addition of ODN-CpG after anti-inflammatory treatment (6.3 ± 3.8 vs. 7.3 ± 3.7, p = 0.1). TLR9 expression was positively correlated with IBD disease severity (r = 0.681, p < 0.0001).

Conclusions

TLR9 expression in memory B from IBD patients is elevated and associated with disease severity.     

Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: A randomized controlled trial

Objective

To evaluate the effects of escitalopram 10–20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes.

Study design

A double-blind, placebo-controlled randomized trial of escitalopram 10–20 mg/day vs. identical placebo was conducted among 205 women ages 40–62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010.

Main outcome measures

The primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG).

Results

Outcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of −0.41; 95% confidence interval (CI) −0.71 to −0.11; p < 0.001), as well as Vasomotor, Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference −0.75; 95% CI −1.28 to −0.22; p = 0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of −0.33; 95% CI −0.81 to 0.15; p = 0.045).

Conclusions

Treatment with escitalopram 10–20 mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain.     

Effects of raloxifene and hormone replacement therapy on forearm skin elasticity in postmenopausal women

Objectives

Hormone replacement therapy (HRT) increases skin elasticity in postmenopausal women. However, the effects of raloxifene, a selective estrogen receptor modulator (SERM), on skin degenerative changes in postmenopausal women remain unknown. We investigated whether raloxifene increases skin elasticity, similar to HRT, in postmenopausal women.

Methods

In a 12-month trial, 17 postmenopausal women (mean age, 66.4 ± 7.8 years) received continuous raloxifene treatment (60 mg/day), 19 women (56.2 ± 6.4 years) received continuous 17-β estradiol treatment using a patch (0.72 mg/2 days) plus cyclic medroxyprogesterone acetate (2.5 mg/day, for 12 days/month), and 11 women (58.1 ± 7.3 years) did not receive either therapy. In each subject, the skin elasticity of the forearm was measured using a suction device at baseline and at 12 months after the start of the study.

Results

Raloxifene and HRT significantly increased skin elasticity from 52.4 ± 3.8% and 64.1 ± 7.2% at baseline to 55.1 ± 4.7% and 67.4 ± 7.4% after 12 months, respectively (P < 0.05, each), but the untreated subjects did not exhibit any significant change in skin elasticity during the study. The delta value for skin elasticity was significantly higher among the raloxifene and HRT subjects than among the untreated subjects (P < 0.05, each).

Conclusions

These findings suggest that raloxifene may have a beneficial effect on skin elasticity, which undergoes degenerative changes in postmenopausal women, in addition to its effects on bone metabolism.     

Evaluation of a novel educational strategy,including inhaler-based reminder labels,to improve asthma inhaler technique

Objective

To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients.

Methods

Thirty-one pharmacists received brief workshop education (Active: n = 16, Control: n = 15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months.

Results

At baseline, patients (Active: 53, Control: 44) demonstrated poor inhaler technique (mean ± S.D. score out of 9, 5.7 ± 1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. Control patients (2.8 ± 1.6 cf. 0.9 ± 1.4, p < 0.001), and asthma severity was significantly improved (p = 0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient–pharmacist relationship.

Conclusion

A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes.

Practice implications

Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.