Study Protocol for a Randomized Controlled Trial of Choral Singing Intervention to Prevent Cognitive Decline in At-Risk Older Adults Living in the Community.

Introduction: This study is a parallel-arm randomized controlled trial evaluating choral singing's efficacy and underlying mechanisms in preventing cognitive decline in at-risk older participants. Methods: Three-hundred and sixty community-dwelling, non-demented older participants are recruited for a 2-year intervention. Inclusion criteria are self-reported cognitive complaints, early cognitive impairment based on neuropsychological test scores or multiple risk factors of dementia. Participants are randomized to either weekly choral singing sessions or general health education. The primary outcome is cognitive performance, measured by a composite cognitive test score (CCTS). Secondary outcomes include depression, anxiety and neuropsychiatric symptoms; perceived stress; sleep quality and severity of dementia symptoms. Underlying mechanisms are examined using blood- and urine-based biomarkers and neuroimaging. Results: Screening began in July 2016. The first group of participants (n = 93) have been recruited. Intervention and control treatments are ongoing and will end in December 2019. Discussion: An evidence-based singing intervention for dementia prevention holds potential for healthcare savings and societal welfare. Trial Registration: NCT02919748, IRB Approval Number: NUS 2508.

Effects of oral contraceptives containing 50 microgram estrogen on blood coagulation in non-Caucasian women.

In one of the first longitudinal studies of 163 non-Caucasian women, comprehensive coagulation, fibrinolysis and platelet function tests were performed before and during 24 months of oral contraceptive pill usage containing 50 microgram estrogen. Results of this ongoing study indicate a state of abnormal coagulability with increase in fibrinogen, prothrombin, Factor V and Factor X. There was also a decrease in antithrombin III level. There was a shortening of overall clotting parameters measured by prothrombin time and Kaolin cephalin time. The significance of these changes in the aetiology of thromboembolism is discussed.

PIP: 163 non-caucasian women in Singapore were studied in the first of a series of longitudinal studies to determine effects of 50-mcg estrogen oral contraceptive (OC) formulations on blood coagulation in these women as compared with effects reported in caucasian women. 2 of the formulations contained hilots interviewed were active in giving hakop 50 mcg of ethinylestradiol. Comprehensive coagulation, fibrinolysis, and platelet function tests were performed during the first 24 months of OC use (all combined formulations). Prothrombin time was significantly reduced only after 12 months of use. The Kaolin cephalin clotting time was reduced and was significant from the 3rd month (P .0005). The thromboelasticity, as shown by thromboelastography, showed no significant alternation in pattern in most patients. There was an increase in fibrinogen level which was significant from the 3rd month (P .025). Factor V and X were significantly increased from the 3rd month (P .0l and P .0l, respectively). And factor II was only significantly increased in the 3rd and 6th month (P .0l) before reverting to pre-OC levels. Factor VII and VIII were not significantly changed, although there was a tendency to rise; at 2 years, the rise was significant for factor VIII. Antithrombin III levels were reduced significantly from the 9th month, and alpha macroglobulin tended to rise, but not significantly. Plasminogen level was significantly increased (P .005). Spontaneous fibrinolytic activity and euglobulin fraction were increased (P .05 for both). Fibrinogen degradation products were unchanged, until after 2 years, when they rose significantly. The number of platelets was significantly increased (P .02) after 9 months, except for a sudden decrease at 24 months. No changes in aggregation or adhesiveness were noted, except for the latter at 24 months.

The use of intradepartmental audit to contain cesarean section rate.

In one department practicing critical review of indications for cesarean delivery, the overall LSCS rate was maintained at 12.3%, 11.1%, 11.2% and 11.4% for 1987, 1988, 1989 and 1990, respectively. A highly significant (P = 0.0013) reduction of 26.8% was observed in the LSCS rate for cephalo-pelvic disproportion between 1987 and 1990. Perinatal mortality rate per 1000 births remained low at 8.25, 7.05, 9.39 and 5.83 for infants weighing 500 g or more.

Coagulation studies in Asian women using injectable progestogen for contraception.

Coagulation, fibrinolytic activity and platelet function were studied in 104 Asian women volunteers who received 150 mg of depot medroxyprogesterone acetate intramuscularly every three months for two years or more. The results were compared with those in matched controls. There was a paucity of change in coagulation factors. The fibrinogen levels were increased and prothrombin time was shortened. The fibrinolytic activity, as shown by the euglobulin clot lysis time, was significantly increased. This latter change contrasts with the many reports concerning Caucasian women and may reflect an increase in fibrinolytic potential in Asian women.

The use of bromocriptine in hyperprolactinemia and galactorrhea in Singapore.

Ninety-four women and seven men were treated with low dose bromocriptine for (a) hyperprolactinemia or (b) normoprolactinemia but with galactorrhea and a pituitary adenoma. All the pituitary adenomas became smaller or remained the same. Prolactin levels decreased with treatment and inappropriate galactorrhea improved in the 53 patients except for 7 where there was no change. Of the 41 women with premenstrual mastalgia 78% improved with treatment. Of the 74 women with ovulatory problems, a biphasic pattern was restored in 65 patients. Thirty-two patients out of the 92 trying to conceive achieved a pregnancy with an abortion rate of 12.5% and non-lethal congenital abnormality of 9.8% (2.1% in Singapore population). Fertility was restored in 3 hyperprolactinemic oligospermic males and improved libido was professed by most of the treated men. Side effects were present but were on the whole tolerable. Pregnancy rate was better in those with high levels of prolactin (greater than 1000 miU/l) than in those with hyperprolactinemia of between 500 and 1000 miU/l although this was not statistically significant chi 2 = 0.69. In the lower hyperprolactinemic range there was noticeable number of patients with endometriosis and increased luteinizing hormone (LH) levels.

Maternal death associated with hydatidiform molar pregnancy.

Three maternal deaths with hydatidiform molar pregnancies associated with severe hemorrhage and coagulopathy are described. Symptoms of coagulation abnormalities are few in mild degrees of intravascular coagulation. This paper addresses the importance of anticipating a coagulopathy in hydatidiform molar pregnancy even before evacuation of the abnormal conceptus since evacuation aggravates fibrinolytic activity and therefore increases hemorrhage in these conditions.

A successful pregnancy from the oocyte donation programme in Singapore General Hospital.

A 41-year-old Chinese woman was seen in our centre in June 1989 with 5 years of premature menopause, requesting ovum donation. She was placed on cyclical hormonal therapy and put on the waiting list for ovum donation. Excess ova became available through one of our IVF patients and were fertilised with her husband's semen. Four pre-embryos resulted and these were cryopreserved using 1,2 propanediol. Embryo transfer in her second cycle of trying on 16 March 1990 of 2 pre-embryos was successful and a singleton pregnancy resulted. The pregnancy was supported with estradiol valerate and intramuscular progesterone till 17 weeks of gestation. The pregnancy went on uneventfully and she delivered a healthy baby boy by Caesarean section on 21 December 1990.

Non-puerperal uterine inversion--a case report.

A rare case of non-puerperal uterine inversion caused by a large fundal leiomyoma in a 36-year-virgo intacta resulting in intractable haemorrhage was reported. After a myomectomy, attempts to reduce the inversion vaginally by transecting the anterior and posterior cervix was unsuccessful and a laparotomy was performed. The inversion was successfully corrected with return of normal function of the uterus.

Comparative study on the effect of Diane and Microgynon 50 contraceptive on the haemostatic mechanisms in Chinese subjects.

A longitudinal controlled study on the effect of Diane and Microgynon 50 (Micro 50) contraceptive pills on the haemostatic mechanisms in 59 Chinese subjects was carried out. Diane, containing the potent anti-androgen progestagen, cyproterone acetate was used as a contraceptive and in subjects requiring anti-androgenic treatment and fertility control. Enhanced fibrinolytic activity with raised plasminogen and alpha 1-antitrypsin (a1-AT) was observed in all subjects after pill treatment. The changes observed after Diane treatment suggests a predispostion to hypercoagulation as evidenced by increases in Fibrinogen, Factors VII and X with accelerated Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and Reaction and Clotting Time (r + k). Maximum elasticity of the clot was raised after Diane 50 treatment when compared with pre-treatment levels. More changes in haemostasis were seen after treatment with Diane containing 35 ug and 50 ug ethinyl estradiol (EE) formulation than during Micro 50 treatment. The results from this study show that Diane even with 35 ug EE formulation caused coagulation changes which were more pronounced than the 50 ug EE Microgynon. The finding is at variance with others that ascribe haemostatic changes observed to increased oestrogen content in a given pill formulation and so merits confirmation in a larger study.

Review on coagulation in trophoblastic disease.

Problems of haemostasis associated with abnormal pregnancy states such as eclampsia, prolonged intrauterine death and amniotic fluid embolism causing maternal death are well recognised. Coagulation problems have been suspected in hydatidiform molar pregnancies previously but because of the rare occurrence, the importance of defective haemostasis in this trophoblastic disorder has not been emphasised. Evidence from clinical course of the disease, from haematological studies and from postmortem findings provide evidence that enhanced coagulation occurs in all hydatidiform molar pregnancies. Secondary fibrinolysis in the intact mole increases during evacuation and could aggravate the coagulation state. If there should already be a moderate degree of intravascular coagulation, it could progress to an irreversible state with evacuation if the coagulation defect are not corrected before the procedure as illustrated by reported maternal deaths. Since the degree of vaginal bleeding does not definitely indicate the degree of coagulopathy, coagulation screening tests are necessary to detect the condition in all hydatidiform moles. The placental proteins with coagulation and fibrinolytic activity found in trophoblastic disease, may be associated with the aetiology of coagulation disorder and may have a prognostic value in detecting subsequent malignancy.

Delayed interval delivery in a triplet pregnancy: a case report.

The incidence of multiple pregnancies is increasing due to a surge in the availability of assisted conception techniques. Spontaneous miscarriages, preterm labour and delivery are common complications of multiple pregnancies. In rare circumstances where the leading foetus has been expelled and the rest remain in utero, it is conventional to augment uterine activity to expel the rest of the uterine contents so as to avoid sepsis. Conservative management in such circumstances might allow for foetal lung maturity in the remaining foetuses, but there is limited experience in the world literature. We present a case of conservative management of a triplet pregnancy with early loss of the leading triplet. The delivery interval was 34 days and both remaining triplets survived without any sequelae.

Clinical aspects of a successful embryo cryopreservation programme from IVF cycles in Singapore General Hospital.

An analysis in November 1991 showed a successful cryopreservation programme between May 1989 and October 1991 in Singapore General Hospital. This programme has resulted in 9.1% more pregnancies in addition to those from conventional in-vitro fertilisation (IVF) methods, increasing pregnancy rates during the same period, from 27.8% per IVF cycle to 36.9% per cycle. The current policy is to transfer 3 fresh embryos in the IVF cycle and freeze the remainder using a modified Testart's method. Clinical factors that influence the success rate include the number of embryos transferred, stage of development of embryos and genital tract infections. Age of patient and grade of embryos did not seem to have affected pregnancy rates. Patients with anovulatory cycles enjoy similar pregnancy rates using a regulated cycle regime for frozen-thawed embryo transfer.

Study of the effects of occupation and industry on sperm quality.

Most of the environmental exposures known to affect testicular function and/or male fertility are to pharmacologic agents, alkylating agents and antitestosterone agents. There are however, few firmly-based associations with occupational exposure. The aim of this study was therefore to determine if there is any association between different semen parameters (viz. sperm count and motility) in relation to occupations and industrial groupings. A total of 614 subjects who attended an andrology clinic were studied. The investigation included a detailed occupational history, clinical examination and seminal analysis for volume, sperm count, and sperm motility. Each subject's last occupation and the industry he represented was classified according to the standard classification code of the Singapore Standard Occupational Classification (SSOC) and the Singapore Standard Industrial Classification (SSIC), respectively. The results showed that subjects who worked as "plant and machine operators" had a significantly higher risk of oligozoospermia, with an adjusted (for age, smoking, medical history, and testicular size) odds ratio (OR) of 1.93 (1.12-3.30), as compared with other occupational groups. Exposure to excessive heat was a possible factor for the poorer sperm count. "Senior officials and managers" were less likely to have poor sperm count, adjusted OR = 0.52 (0.32-0.84), compared to individuals from other occupations. As for abnormal sperm motility, workers from the "transport and communication" industry had significantly higher adjusted OR of 1.80 (1.08-3.00) when compared to the other occupational groups. This could not be attributed to excessive noise, heat or solvent exposure at the workplace.

Research and development in obstetrics & gynaecology in the Department of Obstetrics & Gynaecology at the National University of Singapore.

This is a review of the research and achievements of the Department of Obstetrics and Gynaecology, National University of Singapore since 1949. The research activities reviewed are Fertility Control, Subfertility, Reproductive Endocrinology, In-Vitro Fertilization, Trophoblastic Disease, Prostaglandins and Perinatal Medicine. The University Department has kept abreast with the Singapore norm of two-child families by providing the most sophisticated technology and expertise. The perinatal mortality and stillbirth rates have been reduced to 11 and 6 per thousand births. Prostaglandin research in the Department includes an investigation of the involvement of these substances in various physiological processes, pharmacological studies with different prostaglandins and development of clinical applications. Between 1974 and 1981 we had studied 12 intrauterine contraceptive devices, both on a departmental basis and in conjunction with international agencies. The newer medicated devices have proved to offer significant advantages over the original inert plastic configuration. Metabolic changes in Singapore women on the oral pill and injection Depoprovera were studied. Impaired glucose tolerance and raised fasting total lipids were found in women on the pill. Marginal changes in carbohydrate metabolism only were found in women on injection Depoprovera. Hypercoagulation changes in the blood occurring in Singapore women varied with the dose of the synthetic or natural oestrogen medication. Initially, the fibrinolytic activity was enough to compensate for these changes; however after two years there were signs of decompensation. Progestogens affect coagulation via their influence on the liver functions. Hypercoagulation changes also occurred in pregnancy and was of a greater magnitude than oestrogen or progestogen medication. In many obstetric disorders, including hydatidiform mole, there was evidence of intravascular coagulation. The introduction of endocrine function tests has greatly improved patient care in our Department, in particular those related to endocrine disorders. Application of the immunoassays to basic research has shown that physiological levels of oestradiol exert a negative feedback effect on both FSH and LH secretions in men. The greater suppression of LH than of FSH secretion by pharmacological doses of estradiol is possibly due to different control mechanisms in the pituitary for the synthesis and release of both gonadotrophins. Physiological level of testosterone per se has a definite negative feedback effect on the secretion of LH but not on FSH. Pharmacological doses of the 5-alpha-reduced metabolites of testosterone have been shown to suppress both LH and FSH indicating that some of the actions of testosterone could be medicated by these metabolites of which the 3 alpha-androstanediol and 3 beta-androstanediol are the more likely candidates.