A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

脾内血管的应用解剖学研究盐酸喹那普利治疗原发性高血压的临床应用观察

目的　探讨盐酸喹那普利 (QuinaprilHydrochloride)治疗轻、中度原发性高血压的有效性和安全性。方法　全国 6家医院参加的一项多中心、随机、双盲、平行组间对照研究。结果　 113例原发性高血压病人治疗 8周后 ,总有效率达 85 84% ,统计学有显著性差异。盐酸喹那普利副反应较轻 ,对肾脏、肝脏、造血系统和心脏未见有害作用。结论　盐酸喹那普利是一种安全、疗效好、副反应小的治疗轻、中度原发性高血压的有效药物。     

A New Statistical Method for Dose-Finding Based on Efficacy and Toxicity in Early Phase Clinical Trials

Most statistical methods for dose-finding in phase I clinical trials determine a maximum tolerable dose based on toxicity while ignoring efficacy. Most phase II designs assume that an acceptable dose has been determined and aim to estimate treatment efficacy, possibly with early stopping rules for safety monitoring. The purpose of this paper is to describe a new statistical strategy for dose-finding in single-arm clinical trials where patient outcome is characterized in terms of both response and toxicity. The strategy, which may be considered a phase I/II hybrid, was first proposed by Thall and Russell [1] and subsequently modified by Thall [2]. The underlying mathematical model expresses the probabilities of response and toxicity as interdependent functions of dose. The method is based on fixed standards for the minimum probability of response and the maximum probability of toxicity appropriate for the particular trial. The best acceptable dose is chosen for each successive patient cohort adaptively, based on the fixed standards and the dose-outcome data from patients treated previously in the trial. The scientific goals are to select one best acceptable dose for future patients and to estimate the response and toxicity probabilities at that dose, or to stop the trial early if it becomes sufficiently unlikely that any dose is both safe and efficacious. An application of the method to a trial of donor lymphocyte infusion as salvage therapy for chemo-refractory AML/MDS patients is described. To illustrate the method's flexibility and potential breadth of application, two additional examples are provided, including a hypothetical trial in which a 5% response rate is of interest.     

Bromocriptine in Parkinson disease: further studies

Bromocriptine was administered to 66 patients with advanced Parkinson disease (PD) and increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Forty-five patients tolerated at least 25 mg per day of bromocriptine (the "adequately treated" group) in addition to Sinemet and had significantly decreased rigidity, tremor, bradykinesia, gait disturbance, and total score, but increased involuntary movements. Twenty-five of these 45 patients improved by at least one stage. Among the 45 patients, 27 had "on-off" effects, and in 19 the "on-off" effects decreased on bromocriptine. The mean dose of bromocriptine in adequately treated patients las 47 mg, permitting a 10 percent reduction in the dose of levodopa. Twelve adequately treated patients received bromocriptine for at least 1 year, and 8 continued for longer than this. Bromocriptine was discontinued in 29 of 66 patients because of adverse effects, including mental changes (14 patients) and involuntary movements (9 patients). All adverse effects were reversible. Despite adverse effects, expense, and scarcity, bromocriptine, when added to levodopa, is useful in patients with advanced disease who no longer respond satisfactorily to levodopa, and for whom no other treatment is available.     

Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.