Clinical trial with a new low oestrogen combined oral contraceptive

Summary

An oral contraceptive combination of 30 μg. ethinyl oestradiol and 150 μg. D-norgestrel was studied in 98 patients over 1216 cycles. No pregnancies were reported during the trial period. Cycle control was good: 96.7% of cycles were 28 ± 3 days with a mean duration of menstrual bleeding of 4.3 days. Bleeding irregularities were not marked; amenorrhoea occurred in 1.7% of cycles, spotting in 5.4% and breakthrough bleeding in 5.8 %. The incidence of side-effects commonly associated with combined oral contraceptives was also low.

The author concludes, therefore, that this new lower-dose combination is an effective and relatively trouble-free ovulation inhibitor.     

Clinical and biochemical investigations of a variable-dose combined type oral contraceptive

Summary

A 21-day treatment cycle oral contraceptive of variable composition was administered to 68 healthy young women, each of whom completed 6 cycles of treatment. For the first 11 days, the product contained 50 fig levonorgestrel plus 50 fig ethinyl oestradiol, then for treatment days 12 to 21, 125 fig levonorgestrel plus 50 fig ethinyl oestradiol. Cycle control was good with a mean length of 27.9±1.1 days. Breakthrough bleeding occurred in 1.2% of cycles, spotting in 2.8%, and amenorrhoea in 0.5%. There were no serious side-effects. A series of biochemical tests conducted on fasting blood specimens indicated metabolic changes similar to those seen with other 50 fig oestrogen oral contraceptives.     

Preliminary experience with a new low-oestrogen content combined oral contraceptive

Summary

A new combined oral contraceptive, (‘Restovar’, Organon), consisting of 37.5 μg. ethinyl oestradiol and 0.75?mg. lynestrenol, was taken by 335 women for a total of 4857 cycles. No pregnancies occurred during the study. Satisfactory cycle control with a very low incidence of side-effects was observed. The study proved that with less than 50 μg. of ethinyl oestradiol in the combined formula a high contraceptive efficacy as well as a satisfactory cycle control were obtained.     

The glycemic/metabolic responses to meal tolerance tests at breakfast,lunch and dinner,and effects of the mitiglinide/voglibose fixed-dose combination on postprandial profiles in Japanese patients with type 2 diabetes mellitus

Background: Meal tolerance tests (MTTs) are usually conducted at breakfast after overnight fasting in type 2 diabetes mellitus (T2DM) patients, but differences in postprandial glycemic responses between meals have been reported.

Objective: We conducted MTTs at breakfast, lunch, and dinner to examine the effects of a fixed combination of 10 mg mitiglinide/0.2 mg voglibose (the combination) on glycemic/metabolic responses to meals during the day in T2DM patients. MTTs with unified meals were conducted in 11 T2DM patients before and after 4 weeks of treatment with the combination administered thrice daily before meals. Glycemic/metabolic profiles measured before and at 30, 60, and 120 min after each meal were compared between each meal and between the baseline and treatment periods.

Results and conclusion: The combination significantly reduced postprandial hyperglycemia after each meal. Postprandial AUC_{0 – 120 min} for insulin significantly decreased after lunch and dinner compared with after breakfast, while insulin levels significantly increased at only 30 min after breakfast and dinner. The combination also significantly increased postprandial C-peptide and active glucagon-like peptide-1 levels, and reduced free fatty acid and triglyceride levels, but did not significantly affect glucagon levels compared with baseline, confirming that treatment with the combination improves postprandial responses in Japanese T2DM patients.     

Clinical investigation of the biological effects of a new combination low-dose oral contraceptive (‘Ovostat E’)

Summary

Eleven healthy fertile women volunteers, aged 20 to 30 years, participated in a long-term investigation over 12 cycles into the effects of a low-dose contraceptive containing 1?mg lynestrenol and 0.050?mg ethinyl oestradiol per tablet. Urinary LH, pregnanediol and oestrogen, and serum progesterone and oestradiol values were estimated, and vaginal smears and endometrial biopsies taken, according to a fixed schedule, on the third, sixth, seventh and twelfth treatment cycles. SGOT and SGPT values were also determined. On the basis of the hormonal determinations, it was established that ovulation was inhibited in all the cycles studied. Examination of the endometrial biopsies showed a drug effect in all cases and there was no secretory activity in any of the samples. Hypoplasia was found in 6 out of a total of 22 samples. The karyopyknotic index curve in the vaginal cytology was clearly biphasic and resembled the normal cyclic curve. The indices showed a clear decrease during the sixth treatment cycle, but rose a little during the twelfth. The results confirm the clinical findings that this low-dose steroid combination is effective for contraceptive use.     

Clinical investigation of a very low dosage oral contraceptive combination: 0 75 mg lynestrenol and 0 0375 mg ethinyl oestradiol

Summary

A trial was carried out in 3 clinics to test the efficacy of and cycle control obtained with a very low dosage oral contraceptive combination of lynestrenol (0.75?mg) and ethinyl oestradiol (0.0375?mg). A total of 134 healthy, fertile women, ages ranging from under 19 years to over 40years, participated and completed 1144 treatment cycles.

No pregnancies occurred. The length of the treatment cycle compared to the cycle length before treatment was unchanged in 79.3% of cases. Withdrawal bleeding occurred in 93.1 % of all treatment cycles, and in 78.9% of cases the duration of the withdrawal bleeding corresponded to that of the bleeding before treatment. The proportion of irregular bleeding in the first treatment cycle was 51.4%, but by the 12th treatment cycle this was reduced to 12.5 %. Side-effects, when they did occur, were very slight; existing complaints clearly decreased during the treatment.     

Growth hormone responses to GABAB receptor stimulation throughout the menstrual cycle of healthy females

Growth hormone (GH) responses to the GABA_B agonist baclofen (10 mg) were assessed in six normally cycling, healthy women at three different sex steroid phases of the menstrual cycle: early follicular, pre-ovulatory and luteal. The design was placebo-controlled, balanced and single-blind with a total of six tests being carried out on each subject in two consecutive menstrual cycles. GH responses to baclofen increased incrementally from early-through mid- to late-cycle: 10.95 ± 0.95 μg/l, 24.53 ± 4.73 μg/l, 31.36 ± 3.37 μg/l respectively (p < 0.04). Responses between early- and mid-cycle and early- and late-cycle were significantly different (p < 0.05). There was a direct relationship between baclofen/GH responses and both plasma oestradiol (E₂) concentrations (p = 0.05) and plasma progesterone concentrations (p = 0.02). Responses to placebo did not vary. E₂ has been demonstrated to exert a priming influence on GH responses to many pharmacological and physiological stimuli. An E₂-induced priming effect on GH secretion may underlie these results. Progesterone may augment this effect. Other possible influences are a sex steroid effect on somatostatin or GABA neurotransmission.     

Lansoprazole versus ranitidine for the treatment of reflux oesophagitis

Background: Lansoprazole is a H⁺, K⁺-ATPase (proton pump) inhibitor with an anti-secretory action and is therefore potentially useful in the treatment of gastro-oesophageal reflux. Methods: This study was conducted to determine the efficacy and short-term safety of lansoprazole at doses of 30 mg or 60 mg once daily, compared with ranitidine 150 mg twice daily, in the treatment of patients with reflux oesophagitis. This was a double-blind, stratified, randomized, comparative, parallel group study conducted in five centres in the UK. A total of 229 patients (155 men) aged 18–79 years with endoscopically-confirmed oesophagitis were randomized to receive lansoprazole 30 mg p.o. daily, lansoprazole 60 mg p.o. daily, or ranitidine 150 mg p.o. b.d. Efficacy was assessed by endoscopic examination at 4 weeks and 8 weeks, together with symptom relief and antacid usage. Results: Lansoprazole 30 mg and 60 mg were superior at 4 and 8 weeks (P < 0.01) to ranitidine in healing reflux oesophagitis: respective healing rates being 84%, 72% and 39% after 4 weeks and 92%, 91% and 53% after 8 weeks. Relief of heartburn with lansoprazole 30 mg and 60 mg was superior to that achieved with ranitidine at both week 4 (P < 0.01) and week 8 (P < 0.02). Sixty-four patients experienced a total of 85 adverse events, one-third of which were considered drug-related. The incidence and severity were similar in the three groups. Conclusion: Lansoprazole 30 mg and 60 mg once daily are more effective than ranitidine 150 mg twice daily in the short-term treatment of reflux oesophagitis.     

博莱霉素联合替莫唑胺治疗脑胶质瘤的疗效观察

目的研究注射用盐酸博莱霉素联合替莫唑胺胶囊治疗脑胶质瘤的临床疗效。方法选取2015年1月—2018年1月海口市人民医院收治的60例脑胶质瘤患者为研究对象,将患者随机分为对照组和治疗组,每组各30例。对照组患者口服替莫唑胺胶囊,150 mg/m~2,1次/d,连续服用5 d,然后停药23 d,再重复给药,1个治疗周期为28 d;治疗组患者在对照组基础上静脉注射注射用盐酸博莱霉素,1支/次,1次/d,连续给予2 d,然后停药26 d,再重复给药,1个治疗周期为28 d。两组患者均接受治疗2个周期。观察两组的临床疗效,比较两组的生命质量测定量表(QLQ-C30)评分和1年生存率。结果治疗后,对照组和治疗组的临床有效率(ORR)分别为46.67%、63.33%,疾病控制率(DCR)分别为66.67%、86.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组认知评分、躯体评分、角色评分、社会功能评分、情绪评分均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组认知评分、躯体评分、角色评分、社会功能评分、情绪评分明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,对照组和治疗组1年生存率分别为46.67%、73.33%,两组比较差异有统计学意义(P0.05)。结论注射用盐酸博莱霉素联合替莫唑胺胶囊治疗脑胶质瘤具有较好的临床疗效,能改善生活质量,延长患者生存期,具有一定的临床推广应用价值。     

The contraceptive effects of a new low-dose combination type oral contraceptive

Summary

A study was carried out in 9 women volunteers to investigate the central and peripheral effects of a low-dosage oral contraceptive combination of 0.75?mg lynestrenol plus 0.0375?mg ethinyl oestradiol given for 22 days per cycle over a period of 6 cycles. The results of assessments of a number of hormonal, vaginal and cervical parameters showed that this combination has a two-fold effect: a central effect on the pituitary and a peripheral effect on the ovaries and on endometrial development. The findings of an effect on cervical mucus, as with higher dose combinations, were not sufficiently consistent to warrant a claim for a cervical barrier. The preparation appeared to be well tolerated but there was a high incidence of irregular bleeding in the first treatment cycle. In most of the women, however, this had corrected itself by the second cycle.     

Patent Evaluation: Novel Compositions for the Improved Gastrointestinal Absorption of Antibiotics

Summary

Novelty: Oral antibacterial compositions containing a penem or carbapenem antibiotic in combination with an absorption improver, are disclosed. The absorption improver is selected from substances able to inhibit the dipeptidase localized on or in epithelial cells of the small intestine.

Biology: The degradation of a penem in vivo in rat epithelial cell isolated by citric acid from the small intestine was assayed by HPLC. After 60 minute incubation of 9 μg/ml of the penem and 35 μg/ml of cilastatin, 7.38 μg/ml of the free acid of the penem was measured, compared to 2.08 μ/ml remaining on addition of the penem alone. Five in vivo tests on Sprague-Dawley male rats and two tests on dogs are described. Six of the tests appear to shown an increase in the area under the plasma concentration time curve with the use of an absorption improver.

Chemistry: The use of cilastalin, glutathione and N-acetyl-L-cysteine are specifically claimed. No antibiotics are specifically claimed.     

清热通淋胶囊联合头孢替唑钠治疗泌尿系统感染的临床研究

目的探索清热通淋胶囊联合头孢替唑钠治疗泌尿系统感染的临床效果。方法选择2016年7月—2018年7月武汉市红十字会医院接诊的泌尿系统感染患者178例,按就诊顺序分为对照组(89例)和治疗组(89例)。对照组静脉滴注注射用头孢替唑钠,2.0g加入生理盐水250mL,2次/d;治疗组在对照组基础上餐后半小时口服清热通淋胶囊,4粒/次,3次/d。两组患者均持续治疗5 d。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分和部分生化指标。结果治疗后,对照组和治疗组的总有效率分别为76.40%和86.52%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者尿急、尿痛、尿频症状评分均明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组尿频、尿急、尿痛症状评分均明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者尿白细胞计数、降钙素原和C-反应蛋白水平均显著降低(P0.05),且治疗组这些生化指标比对照组降低更明显(P0.05)。结论清热通淋胶囊联合注射用头孢替唑钠对泌尿系统感染疾病具有良好的治疗效果,具有一定的临床推广应用价值。     

Clinical evaluation of a new oral contraceptive, ‘Pregnon’

Summary

‘Pregnon’, a new oral contraceptive containing 1?mg. lynestrenol and 0.05?mg. ethinyl oestradiol, was administered cyclically to 639 women of fertile age over a total of 9,159 cycles.

There were no pregnancies. In most cases the withdrawal bleeding resembled normal menstruation. The incidence of metrorrhagia was relatively low and when it did occur it was usually confined to the early treatment cycles and was of very limited duration. The objective and subjective tolerance was excellent.     

百乐眠胶囊联合艾司唑仑治疗失眠症的疗效观察

目的探讨百乐眠胶囊联合艾司唑仑治疗失眠症的临床疗效。方法选取2016-2018年到云浮市人民医院接受治疗的210例失眠症患者,根据给药不同将所有患者分为3组,每组患者70例。百乐眠组口服百乐眠胶囊,4粒/次,2次/d;艾司唑仑组晚上入睡前30 min口服艾司唑仑片,1片/次,1次/d;联合组口服百乐眠胶囊联合艾司唑仑片,相关药物服用方法同以上两组。三组患者均连续治疗2周。观察三组的临床疗效,比较三组患者匹兹堡睡眠质量指数(PSQI)和不良反应发生情况。结果治疗后,百乐眠组、艾司唑仑组、联合组总有效率分别是74.28%、82.86%、97.14%,联合组总有效率显著高于百乐眠组、艾司唑仑组,差异有统计学意义(P<0.05)。治疗后,3组患者PSQI评分均有所降低(P<0.05);但治疗后,联合组患者PSQI各评分均显著低于百乐眠组、艾司唑仑组(P<0.05)。百乐眠组、艾司唑仑组、联合组不良反应发生率分别是8.57%、22.86%、10.00%,艾司唑仑组失眠症患者不良反应发生率明显高于百乐眠组、联合组(P<0.05)。结论百乐眠胶囊联合艾司唑仑治疗失眠症具有较好的临床疗效,可显著降低PSQI评分,改善患者睡眠质量,具有一定的临床推广应用价值。     

脑心通胶囊联合依达拉奉治疗心源性脑梗死的疗效观察

目的探讨脑心通胶囊联合依达拉奉注射液与阿司匹林肠溶片治疗心源性脑梗死的临床疗效。方法选取2017年12月—2018年12月西南医科大学附属医院接诊的60例心源性脑梗死患者作为研究对象,按数字表法随机将患者分为对照组和治疗组,每组各30例。对照组患者口服阿司匹林肠溶片,150 mg/次,1次/d,同时口服脑心通胶囊,3粒/次,3次/d。治疗组静脉滴注依达拉奉注射液,30 mg加入0.9%氯化钠注射液100 mL中,2次/d,同时口服脑心通胶囊,3粒/次,3次/d。两组均连续治疗14 d。观察两组患者的临床疗效,比较两组治疗前后的神经功能损伤情况和血流动力学指标。结果治疗后,对照组和治疗组的总有效率分别为76.67%、86.67%,两组比较差异具有统计学意义(P0.05)。治疗后,两组神经功能缺损评分表(NHSS)评分显著降低,日常生活活动能力(ADL)显著升高(P0.05);治疗后,治疗组神经功能损伤评分显著优于对照组(P0.05)。治疗后,两组全血高切黏度、全血低切黏度、血细胞比容、纤维蛋白原水平均显著降低(P0.05);治疗后,治疗组血流动力学指标显著低于对照组(P0.05)。结论脑心通胶囊联合依达拉奉注射液治疗心源性脑梗死具有较好的临床疗效,可促进神经功能恢复,改善血流动力学指标,具有一定的临床推广应用价值。     

Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment

Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain.

Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5?mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125?mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation.

Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409).

Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain.

Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities.     

Patterns of concurrent alcohol,tobacco, and cannabis use in Germany: Prevalence and correlates

Aims: This study investigated past month patterns and risk factors of alcohol, tobacco and cannabis use by level of intensity in the German general population.

Methods: Data from the 2006 German Epidemiological Survey of Substance Abuse (ESA) were used. The cross-sectional random sample consisted of N?=?7912 adults aged 18–64 years. The response rate was 45%. Intensive use of each substance was measured applying substance-specific cut-off points: alcohol: >20/30?g pure ethanol daily for women/men; tobacco: ≥20 cigarettes daily; cannabis: on ≥6 occasions monthly.

Findings: The majority of substance users reported no intensive use of any of the three substances (77.5%) and 19.4% had used one of the three substances intensively. A total of 3.1% engaged in intensive use of multiple substances with alcohol and tobacco (2.3%) as the most prevalent pattern. A higher risk for intensive use of multiple substances was found among males, older individuals and those with a substance use disorder.

Conclusions: Results of this study call for an integrated view on substance use and related disorders in prevention and treatment, taking diverse use patterns and specific needs of substance abusers into account.     

美托洛尔联合稳心颗粒治疗功能性早搏的疗效观察

目的 观察美托洛尔联合稳心颗粒治疗功能性早搏的临床疗效和安全性。方法 选择2011年4月-2013年3月到日照市人民医院就诊的功能性早搏患者90例,随机分成美托洛尔组、稳心颗粒组、联合治疗组,每组均为30例。美托洛尔组口服美托洛尔片12.5 mg/次,2次/d;稳心颗粒组口服稳心颗粒1袋/次,3次/d;联合治疗组口服美托洛尔片和稳心颗粒,用法用量同以上两组。3组均持续治疗4周。观察治疗后两组患者的症状疗效、动态心电图疗效,并对两组患者治疗前后血压、心率及心电图相关指标进行比较。结果 治疗后症状疗效美托洛尔组、稳心颗粒组、联合治疗组总有效率分别为76.6%、83.3%、96.7%;联合治疗组与另两组比较差异均有统计学意义（P<0.05）。动态心电图疗效美托洛尔组、稳心颗粒组、联合治疗组总有效率分别为53.3%、63.3%、76.6%,联合治疗组与另两组比较差异均有统计学意义（P<0.05）。结论 美托洛尔联合稳心颗粒治疗功能性早搏有较好疗效,其临床疗效明显优于单用稳心颗粒和美托洛尔,值得临床推广使用。     

清开灵注射液联合蒙脱石散治疗重症有机磷农药中毒的临床研究

目的探讨清开灵注射液联合蒙脱石散治疗重症有机磷农药中毒的临床疗效。方法选取2016年1月—2018年1月建湖县人民医院收治的60例重症有机磷农药中毒患者作为研究对象,将所有患者根据随机数字表法分为两组,每组各30例。对照组患者口服蒙脱石散,1袋/次,3次/d;治疗组患者在对照组的基础上静脉滴注清开灵注射液,20 mL加入到生理盐水100 mL中,1次/d。两组患者均接受治疗7 d。观察两组的临床疗效,比较两组的临床症状改善情况、生化指标水平。结果治疗后,对照组和治疗组的总有效率分别为76.67%、93.33%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组患者清醒时间、拔管时间、胆碱酯酶(Ch E)活性恢复时间、住院天数和死亡率显著低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者肌酸激酶同工酶(CK-MB)和肌钙蛋白T(CTnT)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者CK-MB和CTnT水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论清开灵注射液联合蒙脱石散治疗重症有机磷农药中毒具有较好的临床效果,能改善临床症状,降低CK-MB和CTnT水平,具有一定的临床推广应用价值。