Treatment of climacteric symptoms in breast cancer patients: A retrospective study from a medication databank

Introduction

Women affected by breast cancer (BC) will often go through menopause at an earlier age and display more frequent and severe symptoms than women who have a natural menopause. The safety of hormone replacement therapy (HRT) and vaginal estrogens for BC survivors has been debated over time and remains unclear. Non hormonal therapies such as antidepressants, gabapentine and clonidine may be useful for those patients but there are few data about their safety.

Aim

This retrospective study analyses the use by BC patients of treatments known to alleviate climacteric symptoms.

Material and method

Post-menopausal Estrogen Receptors positive (ER+) BC patients, aged 45–69, were identified as having bought, at least once, an aromatase inhibitor (AI) or tamoxifen between the years 2000 and 2012 through a pharmaceutical databank in Belgium. Among them, we defined users of a climacteric treatment those who bought, at least once, HRT, vaginal topical estrogens, antidepressants, clonidine and gabapentine.

Results

We identified 2530 BC patients. Among them, 45% were buying a treatment known to alleviate menopausal symptoms. The majority of these treatments were non-HRT therapies. HRT and vaginal estrogens were seldom bought (respectively 1.1% and 6%), but 3% bought vaginal estrogens while buying AI. About 9.2% of tamoxifen users patients bought antidepressants implicated in tamoxifen metabolism at the same time as tamoxifen.

Conclusions

Most BC patients follow current guidelines contra-indicating the use of HRT after BC, they use non hormonal therapies. In some cases they use unfortunately antidepressants that may alter the metabolism of tamoxifen.     

A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women

Objectives

To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1 mg estradiol valerate (1EV) and 2 mg dienogest (2DNG) on the number of moderate and severe hot flushes.

Methods

This study compared the effects of an oral continuous-combined HT containing 1 mg EV and 2 mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks. Data were obtained from 324 postmenopausal women. The primary efficacy variable was the individual relative change of the mean number of moderate and severe hot flushes per week. Weeks 5–12 of treatment were compared with the 2 weeks preceding the treatment phase.

Results

Moderate and severe hot flushes were reduced by 80.8 ± 30.9% in the 1EV/2DNG group and by 41.5 ± 39.4% in the placebo group. This difference was statistically significant (p < 0.0001; Wilcoxon's rank sum test). The incidence of all types of hot flushes (mild + moderate + severe) was reduced by 75.2 ± 30.2% under 1EV/2DNG and by 35.3 ± 37.0% under placebo.In the subset of non-hysterectomized women, exposure to 1EV/2DNG led to 2.4 ± 6.2 days with bleeding in the reference period of 84 days of treatment, versus 0.3 ± 1.3 days in the placebo group.The safety profile of 1EV/2DNG was very similar to that of placebo.

Conclusions

Continuous-combined HT preparation with 1 mg EV and 2 mg DNG induced a significant reduction of moderate and severe hot flushes compared to placebo (p < 0.0001).Thus, this low-estrogen preparation is an effective and safe option for HT.     

A randomized,double-blind,placebo-controlled,crossover study on the effect of oral oestradiol on acute menopausal symptoms

Acute menopausal symptoms occur less frequently in Asian than in Caucasian women. Oestrogen replacement therapy has been shown to be effective in controlling acute symptoms in Caucasians, but the effect of oestrogens is not well documented in Asian women. A randomized, double-blind, placebo-controlled, crossover study of the effect of oral oestradiol on the incidence of acute menopausal symptoms was conducted in 83 Hong Kong Chinese women who had experienced a surgical menopause. Although there was a significant increase in the oestradiol concentration with treatment compared with placebo (P < 0.001), there were no significant differences in the reporting of symptoms between the treatment and placebo groups. There is no obvious explanation for this apparent lack of effect of oestrogen on acute menopausal symptoms in Chinese women. Whilst it may be related to the generally low incidence of symptoms or to a higher dietary intake of phytoestrogens in Chinese women, further studies are necessary to explain these findings.     

A proprietary blend of standardized Punica granatum fruit rind and Theobroma cocoa seed extracts mitigates aging males' symptoms: A randomized,double-blind,placebo-controlled study

Objective: We evaluated the safety and efficacy of a novel combination of Punica granatum fruit rind and Theobroma cocoa seed extracts (LN18178 or Tesnor^®) in enhancing serum testosterone level and reducing aging males'' symptoms (AMS) in a randomized, double-blind, placebo-controlled investigation (CTRI Reg. No. CTRI/2019/02/017506).Methods: One hundred twenty healthy male participants (age 36-55 years) were randomized (n=40) to placebo, 200 or 400 mg of LN18178 for a period of fifty-six consecutive days of supplementation. The primary efficacy parameter was the AMS score. The secondary parameters were serum testosterone (free and total) levels, hand-grip strength, and perceived stress scale (PSS-10) score. Measurement of other hormones included in the study was serum dihydrotestosterone (DHT), cortisol, and 17β-estradiol (E2). Total blood chemistry parameters, vital signs, and urinalysis were parts of the safety assessment.Results: Both doses of LN18178 significantly reduced the mean AMS scores after 56 days of supplementation. Furthermore, it significantly improved general, psychological, and sexual well-being. Serum levels of free testosterone and total testosterone levels were significantly increased in LN18178 supplemented (200 and 400 mg) participants compared to the baseline and placebo. Significant improvements in hand-grip strength and reduced PSS-10 scores were also observed.Conclusion: LN18178 supplementation reduced AMS scores and improved sexual performance. Also, LN18178 groups exhibited superior muscular strength and reduction in perceived stress. Total blood chemistry and urine analysis demonstrated the broad-spectrum safety.     

特异性体液免疫与传染性非典型肺炎患者病情的关系研究

目的：研究传染性非典型肺炎患者特异性体液免疫与其病情的关系。方法：采用间接酶联免疫法和双抗原夹心法检测不同病情SARS患者血清中特异性抗体。结果：间接法重症组SARS患者IgG的效价比轻症组高2．9倍，IgM的效价比轻症组高1．7倍；双抗原夹心法重症组SARS患者特异性抗体的效价比轻症组高2．6倍。可见两种血清学方法的检测结果均是重症组血清特异性抗体的效价显著高于轻症组；间接法重症组SARS患者IgG的阳性检出率比轻症组高58．2％，IgM高22．1％；双抗原夹心法重症组SARS患者特异性抗体阳性检出率比轻症组高53.9％。结论：SARS重症组血清特异性抗体效价显著高于轻症组；重症组血清特异性抗体阳性检出率显著高于轻症组。     

Efficacy and tolerability of Menorest 50 compared with estraderm TTS 50 in the treatment of postmenopausal symptoms. A randomized, multicenter, parallel group study

Two-hundred and five (205) menopausal women with moderate to severe vasomotor symptoms, aged 39–64 years, were randomized from 20 clinical centers. After a 4-week treatment-free period, each woman received a cyclical regimen (25 days of a 4-week cycle) of Menorest^® 50, a new matrix-type transdermal estradiol system or Estraderm^® TTS 50, a marketed reservoir-type transdermal estradiol system twice weekly for 12 weeks. An oral progestin was also given for 10 days each cycle. The objectives were to compare local and systemic tolerability and efficacy in the treatment of menopausal symptoms. One-hundred and ninety-four [194] patients (96 and 98 patients in the Menorest^® 50 and the reservoir transdermal patch groups, respectively) were considered in the intent-to-treat population and 204 (102 in each group) in the safety population. The two treatment groups were comparable with regard to the demographic data and menopausal status. The primary efficacy criteria were the comparison between Menorest^® 50 and the reservoir transdermal patch in erythema and pruritus at application sites and the difference between the treatment groups in the mean number of hot flushes per day at week 12, adjusted for baseline. A statistically significant reduction in the mean number of hot flushes was observed in each group compared with baseline, with a decrease from 6.5 at baseline to 0.3 at 12 weeks and 6.4 to 0.4 in the Menorest^® 50 and reservoir transdermal patch groups respectively; there was no statistically significant difference between the two groups during the 12-week treatment. The severity score of menopausal symptoms was also dramatically improved in each of the two treatment groups. There were no statistically significant differences in the mean plasma estradiol concentrations and mean estradiol to estrone ratio (> 1.0) in both groups after 10 weeks of therapy. A similar number of adverse events was observed in both groups. Menorest^® 50 showed better local tolerability than the reservoir transdermal patch with a lower incidence of topical adverse events, erythema and pruritus. In summary, Menorest^® 50 was as effective as the reservoir transdermal patch in reducing the mean number of hot flushes, and improving the severity of other menopausal symptoms, including vasomotor, psychiatric and urogenital symptoms.     

A randomized, double-blind trial of the effect of treatment with formoterol on clinical and inflammatory parameters of asthma in children.

BACKGROUND: In addition to their bronchodilating effect, long-acting inhaled beta-agonists have recently been shown to have some anti-inflammatory properties. OBJECTIVE: The purpose of this study was to evaluate the effect of formoterol on inflammatory mediators in children. METHODS: In this double-blind, randomized, placebo-controlled trial, 34 children, aged 6 to 18 years, with moderate atopic asthma, were randomly allocated to receive formoterol or matching placebo for 4 weeks. The primary endpoint of this study was to determine changes in serum levels of inflammatory markers after treatment with formoterol; secondary endpoints included clinical efficacy and bronchial hyperreactivity. The following parameters were measured: symptom score, forced expiratory volume in 1 second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) for histamine and peripheral blood eosinophil count, serum levels of eosinophil cationic protein (ECP), soluble receptor of interleukin-2 (sIL-2R), level of interleukin-4 (IL-4), level of soluble intercellular adhesion molecule-1 (ICAM-1), and immunoglobulin E (IgE) level before and after treatment. RESULTS: Compared with placebo, treatment with formoterol significantly improved lung function. The mean value of FEV1 changed from 74% of predicted value before treatment to 80% of predicted value after treatment (P < 0.001). The mean concentration of eosinophil blood count before and after treatment was 379 and 310 cells/mm3 (P = 0.035); ECP was 93 and 83 mcg/L; and serum IL-4 was 0.13 and 0.11 pg/mL (P = 0.001). There was no significant difference between formoterol and placebo recipients in PC20H, and serum concentration of sIL-2R, sICAM-1, or IgE after treatment. The group that received formoterol showed improvement in pulmonary function as measured by FEV1 (P < 0.001), and PC20H (P = 0.04) after 4 weeks of treatment. These patients also showed improvement of clinical symptoms (P < 0.001). Serum marker measurements in the formoterol group showed decreased concentrations of eosinophil blood count, ECP, and IL-4, but there was no difference in before and after measurements of sIL-2R, sICAM-1, and IgE. CONCLUSIONS: These results indicate that formoterol has measurable anti-inflammatory properties and can diminish asthma symptoms and bronchial hyperreactivity.     

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.     

A comparative preliminary biochemical study on the effect of fasciola infestation in bile and serum of Egyptian buffaloes,cows and sheep

Summary Confirming previous morphological observation on the true identity of Fasciola worms in Egyptian buffaloes, cows and sheep, the present preliminary biochemical estimations have succeeded completely to demonstrate, for the first time, the significant analytical dissimilarity of their normal bile and serum and the variable effect of the corresponding groups of worms on the content values of this important habitat and main body fluid.     

Twelve months effect of self-referral to inpatient treatment on patient activation,recovery, symptoms and functioning: A randomized controlled study

ObjectiveTo investigate the effect of having a contract for self-referral to inpatient treatment (SRIT) in patients with severe mental disorders.MethodsA randomized controlled trial with 53 adult patients; 26 participants received a SRIT contract, which they could use to refer themselves into a Community Mental Health Centre up to five days for each referral without contacting a doctor in advance. Outcomes were assessed after 12 months with the self-report questionnaires Patient Activation Measure (PAM-13), Recovery Assessment Scale (RAS), and the Behavior and Symptom Identification Scale (BASIS-32) and analyzed using linear mixed and regression models.ResultsThere was no significant effect on PAM-13 (estimated mean difference (emd) −0.41, 95% CI (CI):-7.49–6.67), nor on the RAS (emd 0.02, CI:-0.27–0.31) or BASIS-32 (0.09, CI:-0.28–0.45). An exploratory post hoc analysis showed effect of SRIT in those with low PAM below ≤47 (p = 0.049).ConclusionThere were no group differences after 12 months, but both groups maintained their baseline levels.Practice implicationsSRIT contracts can be recommended as it supports the rights to self-determination, promote user participation in decision-making in own treatment without any indication of adverse effects.     

Effects of a continuous-combined regimen of low-dose hormone therapy (oestradiol and norethindrone acetate) and tibolone on the quality of life in symptomatic postmenopausal women: A double-blind,randomised study

ObjectiveThis study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women.DesignThis study was a prospective, randomised, double-blind, comparative trial with a control group.SettingThe study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil.PopulationA total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy.InterventionsThe patients were randomised into three groups: (1) daily treatment with 2.5 mg tibolone (n = 64), (2) 50 mg calcium carbonate + 200 IU vitamin D3 (Ca/Vit D3, n = 54) or (3) 1 mg oestradiol + 0.5 mg norethindrone acetate (E2/NETA, n = 56) for 12 weeks.Primary outcome measuresThe primary outcome was the evaluation of QoL using the Women's Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment.ResultsA total of 130 women in the following groups completed the study: tibolone (n = 42), Ca/Vit D3 (n = 44) and E2/NETA (n = 44). An improved QoL based on the WHQ was observed at T0 (80.12 ± 14.04, 77.73 ± 15.3, 77.45 ± 15.4) and T12 (57.0 ± 15.5, 55.7 ± 16.7, 58.4 ± 12.6) for the tibolone, E2 + NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2 ± 26, 5.6 ± 2.8, 5.4 ± 2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2 ± 1.5, 4.0 ± 1.8, 4.3 ± 2.0, respectively, p values <0.05). Adverse effects were few and mild.ConclusionsAn improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.     

A prospective,randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms,psychological well being,and quality of life in postmenopausal Chinese women

OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.     

A double-blind, placebo-controlled study of the effects of lithium on cognition in healthy subjects: mild and selective effects on learning

Background: Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium. The aim of the study was to look at the effect of lithium in normal subjects (N=30) taking lithium for 3 weeks. A comprehensive battery was used to assess attention and memory. Methods: Subjects were randomized to double-blind treatment with either lithium (N=15) or placebo (N=15) for a 3-week period. Thirteen participants in the lithium group and 15 in the placebo group completed the study. The lithium and placebo were administered twice daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The initial daily dose was calculated according to the Pepin formula to achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive performance (attention, memory) was assessed in each subjects during three periods, i.e. at baseline, after 3 weeks of lithium or placebo, and 2 weeks after discontinuation of study medication. Results: In short-term memory tasks, the performance of subjects in the lithium group was worst 3 weeks after lithium treatment compared to 2 weeks after discontinuation. In long-term memory, a significantly higher number of words was recalled by the placebo group but not the lithium group. Conclusions. Lithium may have an effect on learning when long-term explicit memory test are administered repeatedly. It means that the practice effect when a subject performs the same task several times is less in the lithium-treated group than in the placebo group. This practice effect is related to the learning of a task.     

Impact of renal ischemia/reperfusion injury on the rat Kupffer cell as a remote cell: A biochemical,histological, immunohistochemical,and electron microscopic study

Almost all transplanted solid organs are exposed to some degree of ischemia-reperfusion (IR) damage. It is interesting to know that this IR damage affects various remote tissues including the liver and resulted in serious adverse effects. Liver injury triggers different responses of liver tissue especially Kupffer cells (KCs). The goal of this current study is to assess the biochemical and morphological changes of hepatic KCs after the induction of renal ischemia-reperfusion (RIR) and point out their role in remote liver injury after RIR.Sixteen male Sprague-Dawley rats were randomly divided into two equal groups: Group I; sham group. Group II; renal ischemia reperfusion (IR) group in which rats were exposed to renal ischemia for 45 min followed by renal reperfusion for 48 h. Three rats from each group were subjected to charcoal injection to evaluate KCs activity. Specimens of rat liver from each group were obtained and processed for biochemical, light microscopic and ultramicroscopic examination. The current results showed elevated serum levels of AST and ALT. The liver HGF-α protein expression increased in IR group compared to the sham group. In IR group, numerous charcoal labeled KCs were observed mainly localized around the central vein. Scanning electron micrographs showed complex primary and secondary foot process of the KCs. Ultrastructural study showed KCs with multiple cytoplasmic vacuoles, lysosomes and mitochondria, rough endoplasmic reticulum and ribosomes. Immuno-histochemical study showed more tumor necrosis factor-α (TNF-α) expression in KCs than the sham group. These results collectively demonstrated that renal IR produced biochemical and morphological changes in the liver KCs and theses cells might have a role in the remote liver injury after renal IR. This might be one of the mechanisms through which RIR affects the liver.     

A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness

OBJECTIVES: To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period. METHODS: Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy. RESULTS: Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance. CONCLUSIONS: EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.     

A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen

BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. METHODS: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P=0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P=0.22). However, the medication score improved significantly (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.     

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological,immunohistochemical and biochemical study

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.     

术前KLIC评分对清创、假体保留联合抗生素治疗急性假体周围感染效果的预测价值

目的 探讨KLIC（kidney, liver, index surgery, cemented prosthesis and C reactive protein value）评分系统用于预测清创、假体保留联合抗生素方案（DAIR）治疗急性假体周围感染（PJI）结果的准确性。方法 回顾性研究。纳入2015年1月—2020年12月南京大学医学院附属金陵医院骨科急性PJI患者44例,其中男17例、女27例,年龄21~86岁,均行DAIR。结合病史和检验结果,计算患者术前KLIC评分,并按评分结果将患者分为KLIC评分≤2分组、2.5~3.5分组、4~5分组、5.5~6.5分组和≥7分组。比较各组患者基线资料、住院时间和DAIR治疗结果的差异。采用受试者操作特征曲线（ROC）来评价KLIC评分系统预测DAIR治疗结果的准确性;以DAIR失败作为终点事件,采用Kaplan-Meier绘制累积治疗成功率曲线。结果 5组患者年龄、性别、体质量指数（BMI）、病变部位、感染分类、感染症状持续时间、术后住院时间等基线资料比较,差异均无统计学意义（P值均>0.05）。5组患者总体治疗成功率为61.36%（27/44）、失败率为38.64%（17/44）;KLIC评分≤2、2~3.5、4~5、5.5~6.5分和≥7分5组的失败率分别为0/8、2/8、5/13、6/10、4/5,组间比较差异有统计学意义（P=0.018）;趋势χ²检验结果提示,随着KLIC评分的增加,DAIR失败率也随之增加,差异有统计学意义（χ²=10.86,P=0.001）。ROC曲线显示KLIC评分在预测DAIR治疗结果上具有较高的准确性（AUC=0.876,95%可信区间0.773~0.978,P<0.001）。Kaplan-Meier曲线提示：KLIC评分≥7分的患者累积治疗成功率低于KLIC评分<7分者,差异有统计学意义（χ²=8.95,P=0.003）。结论 KLIC评分对于DAIR治疗结果具有良好的预测性;对于KLIC评分≥7分的急性PJI患者,DAIR治疗的失败率较高,不建议采用。