Income disparity in school readiness and the mediating role of perinatal maternal mental health: a longitudinal birth cohort study.

AIMS: There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness. METHODS: Prospective data from 505 mother-child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models. RESULTS: Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034). CONCLUSIONS: Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.

Clinical and economic impact of school-based nonavalent human papillomavirus vaccine on women in Singapore: a transmission dynamic mathematical model analysis.

OBJECTIVE: To examine the epidemiological and economic impact of a nine-valent (nonavalent) human papillomavirus (HPV) 6/11/16/18/31/33/45/52/58 vaccine programme for young teenagers in Singapore. DESIGN: Mathematical modelling. SETTING: Pharmaco-economic simulation projection. POPULATION: Singapore demography. METHODS: Clinical, epidemiological and financial data from Singapore were used in a validated HPV transmission dynamic mathematical model to analyse the impact of nonavalent HPV vaccination over quadrivalent and bivalent vaccines in a school-based 2-dose vaccination for 11- to 12-year-old girls in the country. The model assumed routine cytology screening in the current rate (50%) and vaccine coverage rate of 80%. MAIN OUTCOME MEASURES: Changes over a 100-year time period in the incidence and mortality rates of cervical cancer, case load of genital warts, and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with bivalent and quadrivalent HPV vaccination programmes, nonavalent HPV universal vaccination resulted in an additional reduction of HPV31/33/45/52/58 related CIN1 of 40.5%, CIN 2/3 of 35.4%, cervical cancer of 23.5%, and cervical cancer mortality of 20.2%. Compared with bivalent HPV vaccination, there was an additional reduction in HPV-6/11 related CIN1 of 75.7%, and genital warts of 78.9% in women and 73.4% in men. Over the 100 years, after applying a discount of 3%, disease management cost will be reduced by 32.5% (versus bivalent) and 7.5% (versus quadrivalent). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year gained was SGD 929 compared with bivalent vaccination and SGD 9864 compared with quadrivalent vaccination. CONCLUSION: Universal two-dose nonavalent HPV vaccination for 11- to 12-year-old adolescent women is very cost-effective in Singapore. TWEETABLE ABSTRACT: Nonavalent HPV vaccination of 11- to 12-year-old girls is cost-effective in Singapore.

Vaccine Misconceptions and Low HPV Vaccination Take-up Rates in Singapore.

BACKGROUND: HPV vaccination in Singapore is voluntary and physician prescription-based. This study investigated the current status and intention for HPV vaccination among Singapore nurses. MATERIALS AND METHODS: All female nurses in a general hospital were given an anonymous questionnaire on HPV vaccination experience and intention of vaccinating their daughters. The influence of age, knowledge and perceived-risk of cervical cancer, and cultural background on mother's intention of vaccinating their daughters was analyzed. RESULTS: Of 2,000 nurses, 1,622 (81.1%) responded and analysis was performed on 1,611 with valid data. They showed good awareness on association of cervical cancer with multiple sexual partners (81.9%), history of sexually transmissible diseases (78.2%), and history of genital warts/HPV infection (73.5%), and on cervical cancer preventive effects of HPV vaccination (54.6%). The prevailing misconceptions of the vaccines were: investigational nature (38.9%), side effects (27.9%) and indicated for women at high risk for cervical cancer (20.5%). CONCLUSIONS: Misconceptions on the nature, role and safety of HPV vaccines low vaccine up-take rates and daughters. Dissemination of adequate and accurate HPV vaccine information and a review for school-based vaccination are needed for optimal delivery of HPV vaccines in Singapore.

Application of legal principles and medical ethics: multifetal pregnancy and fetal reduction.

In the management of complex medical cases such as a multifetal pregnancy, knowledge of the ethical and legal implications is important, alongside having competent medical skills. This article reviews these principles and applies them to scenarios of multifetal pregnancy and fetal reduction. Such a discussion is not solely theoretical, but is also relevant to clinical practice. The importance of topics such as bioethical principles and informed consent are also herein addressed.

Alternating hemiplegia of childhood: successful treatment with topiramate and flunarizine, a case report.

Alternating hemiplegia of childhood (AHC) is a rare neurological disorder which usually presents before 18 months of age and is characterised by recurrent alternating episodes of hemiparesis. A single effective treatment for this condition is yet to be established; flunarizine is currently the most widely used but with varying degrees of success. An 18-month-old child presented with AHC and treatment with a combination of topiramate and flunarizine made a significant difference in controlling the frequency and severity of the attacks. This possibly allowed a better developmental outcome than in most children with this condition. Topiramate combined with flunarizine for treating AHC has much potential for further research.

Headache diagnosis, disability and co-morbidities in a multi-ethnic, heterogeneous paediatric Asian population.

This was a questionnaire survey on headache and migraine prevalence in 2873 Singaporean schoolchildren aged 6 to 16 years. ICHD-II headache classification, disability assessment with PedMIDAS and screening of psychosocial co-morbidities with the Paediatric Symptom Checklist were conducted. Lifetime headache prevalence was high at 80.6%, migraine prevalence was 8.6% and tension headache prevalence was 10.0%. Headache and migraine prevalence was high compared with that found in other Asian studies. Factors significantly associated with headache included adolescent age (OR = 1.5 [95% CI 1.3-1.9], p < .001), female gender at primary (OR = 1.4 [95% CI 1.1-1.8], p = .003) and secondary (OR = 1.8 [95% CI 1.3-2.5], p < .001) levels and Malay ethnicity at the primary level (OR = 2.8 [95% CI 1.6-4.9], p < .001). The average PedMIDAS score for headache disability was 3.2 +/- 8.4, and migraine disability (PedMIDAS 8.1 +/- 11.2-15.2 +/- 29.6) was lower than in some studies. Self-medication (20.5%) and use of alternative therapy (59.0%) were high among chronic daily headache sufferers. Routine sleep and stress screening is recommended for children with headaches. Recognition of the influence of genetics, lifestyle and cultural factors on headache management should be emphasized.

Unusually mild phenotype of AADC deficiency in 2 siblings.

Aromatic L-amino acid decarboxylase deficiency is a rare neurotransmitter defect leading to serotonin, dopamine and norepinephrine deficiency. Affected individuals usually present in infancy with severe developmental delay, oculogyric crises and extrapyramidal movements. We present the clinical, molecular and biochemical features of a pair of siblings who presented with fatigability, hypersomnolence and dystonia and who showed excellent response to treatment. Analysis of CSF biogenic amines, plasma AADC levels and direct sequencing of the DDC gene was performed. CSF catecholamine metabolites were reduced, with elevation of 3-O-methyldopa. Plasma AADC activity was undetectable in both siblings, and decreased in their carrier parents. One missense mutation (853C>T) was found in exon 8, and a donor splice site mutation was found in the intron after exon 6 (IVS6+4A>T). Both siblings showed excellent response to MAO inhibitor and dopamine agonist treatment. This report expands the clinical spectrum of AADC deficiency and contributes to the knowledge of the genotype and phenotype correlation for the DDC gene. It is important to recognize the milder phenotypes of the disease as these patients might respond well to therapy.

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro.

Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707-5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (P<0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (P<0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

First-line gemcitabine and carboplatin in advanced ovarian carcinoma: a phase II study.

OBJECTIVES: To evaluate tumour response rate and toxicities of gemcitabine and carboplatin in chemonaive subjects with advanced epithelial ovarian cancer. DESIGN: A phase II study. SETTING: Gynaecologic oncologic unit. POPULATION: Twenty chemonaive International Federation of Gynecology and Obstetrics (FIGO) stage IIIc and stage IV subjects with ovarian cancer. MAIN OUTCOME MEASURES: Tumour response, disease free and overall survival and toxicity. METHODS: Intravenous gemcitabine 1000 mg/m2 on day 1 and day 8 and carboplatin at area under centre (AUC) = 5 on day 1 were administered three weekly for six cycles. Subjects who received more than three cycles of chemotherapy were eligible for assessment of tumour response, while all the cycles of chemotherapy were assessed for toxicities. RESULTS: The mean age of the subjects was 57.3 years, and the median follow up was 38.7 months. Of the 18 eligible subjects analysed, 11 (61.1%) showed a complete clinical response, and the overall response rate was 83.3% (15/18). The median overall survival was 29.2 [95% (confidence interval) CI 22.8-35.6] months, and the median progression-free survival was 11.6 (95% CI 4.7-18.5) months. WHO grade 3 anaemia, neutropenia and thrombocytopenia was 7.6, 9.5 and 0%, respectively, on day 8, and 15.5, 12.2 and 15.5%, respectively, on day 15. Two subjects required a total of three hospital admissions for neutropenic sepsis, and two required five hospital admissions for platelet transfusion for severe thrombocytopenia. CONCLUSION: Chemonaive advanced ovarian cancer showed a high response rate to combined gemcitabine and carboplatin chemotherapy. The subjects developed moderate adverse reactions. Phase III study to evaluate the role of combined gemcitabine and carboplatin as first-line chemotherapy in ovarian cancer is warranted.

Brain metastases from epithelial ovarian cancer.

Brain metastasis from epithelial ovarian cancer is uncommon. We studied the presentation, treatment, and prognosis of brain metastasis in a single institution. A retrospective review of clinical details kept in the computer database of gynecologic oncology services in a tertiary institution between 1993 and 2003 was done. A Medline search for English publications on brain metastasis from epithelial ovarian cancer was performed from 1966 to 2003. The study period included 605 patients, and 4 (0.66%) patients developed brain metastases. The patients were usually well, until they presented with hemiparesis. The median primary treatment to brain metastasis interval was 16.5 months. Three out of four cases had multiple brain metastases, and all had small-volume extracranial tumor relapses. Serum CA125 measurement was not reliable in the screening for brain metastasis. The median survival after brain metastasis was 19.5 months. Single brain metastasis can be treated with surgery. Our experience supports the prevalent published opinion that all other cases should be considered for combined radiotherapy and surgery or radiotherapy and chemotherapy. Surveillance of tumor recurrence with serum CA125 monitoring does not predict brain metastasis, which carries a poor prognosis. The best mode of management of these patients is yet to be determined. Large study with multicenter participation to establish the standard treatment is urgently needed.

Metastatic carcinoma of the cervix presenting as a psoas abscess in an HIV-negative woman.

A case of advanced carcinoma of the cervix presenting as a psoas abscess is described. This unusual presentation has been reported in association with AIDS but is extremely rare in HIV-negative women. This case report emphasises the importance of awareness of unusual causes of the psoas abscess in an era when the classical tuberculous abscess is fast disappearing.

Decreased access to health care and social isolation among young adults with cerebral palsy after leaving school.

OBJECTIVE: To examine if leaving special schools has a negative impact on the health care and social isolation of young adults with cerebral palsy. METHODS: Young adults with cerebral palsy, aged between 15 and 22 years, were divided into 2 cohorts: current students, who were still receiving services from special schools, and school-leavers, who had since been discharged from care. A questionnaire and physical examination were administered to assess the extent of disability, health care received by, and social isolation of these young adults. RESULTS: School-leavers had a greater degree of dissability than did students, although the results were not statistically significant. Health care exposure to specialists, general practitioners, therapists physiotherapists, occupational therapists, and/or speech therapists), and medical social workers decreased after leaving school; with the exception of contact with general practitioners, these results were significant (p<0.05). The entire cohort was more socially isolated than a control cohort. School-leavers participated in fewer activities outside their homes, but showed less concern about their disability than did current students. CONCLUSIONS: Young adults with cerebral palsy continue to have health care and lifestyle needs after leaving school, which are currently not being adequately met.

Sperm segregation patterns by fluorescence in situ hybridization studies of a 46,XY,t(2;6) heterozygote giving rise to a rare triploid product of conception with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype.

A blighted ovum diagnosed initially by ultrasound was determined to be a partial hydatidiform mole with a 69,XXY,t(2;6)(p12;q24)der(6)t(2;6)(p12;q24)pat karyotype by cytogenetic analysis. The triploid state arose through dispermy in which both spermatozoa carried rearranged chromosomes, one carrying a balanced translocation through alternate segregation and the other an unbalanced derivative chromosome 6 through adjacent 1 segregation. Segregation analysis of 7,000 spermatozoa from the father was performed with a three-color fluorescence in situ hybridization (FISH) protocol using alpha-satellite 6, telomeric 2p, and telomeric 6q probes. Segregation frequencies of normal and balanced products (alternate segregation), adjacent 1, adjacent 2, and 3:1 were 49.9%, 42.4%, 2.5%, and 4.2%, respectively. The high percentage of alternate segregation is consistent with the knowledge of their preferential outcome. However, the high incidence of adjacent 1 sperm highlights the abnormality risk. Alternate and adjacent 1 segregations (92.3%) accounted for the observed rearranged chromosomes in the triploid. The most viable imbalanced combination would be the one carrying the der(6) chromosome, but since the unbalanced segment comprises 3.6% of the haploid autosomal length (HAL), no risk of a viable imbalanced offspring is indicated. However, an increased likelihood of recurrent miscarriages is likely, and this is confirmed by the couple's two earlier miscarriages. Sperm segregation patterns of translocation carriers determined by FISH can help in ascertaining expected and unexpected karyotypes. The high frequency of adjacent 1 products shows that the presence of the additional derivative chromosome in the partial mole, though rare in occurrence, should be less surprising.

Pregnancy after renal transplantation: experience in Singapore General Hospital.

INTRODUCTION: Renal transplantation offers the best hope for those women with end-stage renal disease who wish to have children. However, pregnancy after renal transplantation is associated with increased maternal and fetal morbidity. The aim of this retrospective study was to review the outcome of pregnancy in renal transplant patients in Singapore General Hospital. MATERIALS AND METHODS: Forty-two pregnancies, occurring between December 1986 and December 2000, in 25 out of 141 renal transplant women in their reproductive age group (18 to 45 years old) were identified from our high-risk pregnancy record and retrospectively analysed. RESULTS: Thirteen (31%) pregnancies were unsuccessful; 10 abortions, 2 ectopic pregnancies and 1 stillbirth. The remaining 29(69%) successful pregnancies were complicated by maternal anaemia (65.5%), superimposed hypertension (44.8%), premature rupture of membranes (27.6%), urinary (17.2%) and lower genital tract (13.8%) infections, abnormal glucose tolerance test (13.8%), premature delivery (44.8%), low-birth-weight babies (44.8%), small-for-gestational-age babies (20.7%) and intrauterine growth restriction (20.7%). There were no documented cases of multiple pregnancies, congenital anomalies or deterioration of renal function. The outcome of pregnancy was not statistically influenced by preconception renal function and transplant-conception interval. CONCLUSIONS: Successful pregnancy is possible in women after renal transplantation. Such pregnancy is often associated with increased maternal and fetal complications and should be managed by a multidisciplinary approach in a tertiary centre. The function and survival of renal allograft was not adversely affected by pregnancy.

Laparoscopically-assisted vaginal hysterectomy (LAVH)--an alternative to abdominal hysterectomy.

AIM: To study the outcomes of 42 consecutive patients who were scheduled for a laparoscopically-assisted vaginal hysterectomy (LAVH) between I January 1994 to 31 December 1999. METHOD: Retrospective study RESULTS: Two patients required conversion to an abdominal hysterectomy. The range of uteri removed was from six to 16 weeks' size. Menorrhagia was the commonest presenting complaint and uterine fibroids was the commonest diagnosis. The mean duration of surgery (+/- SD) was 131.0 +/- 31.7 minutes. Mean blood loss (+/- SD) was estimated at 417 +/- 169 mls. Six percent of patients required a perioperative blood transfusion. Fifty-five percent of patients did not require any injectable analgesics and 45% were able to ambulate on the day of surgery. The mean duration of hospital stay (+/- SD) was 4.2 +/- 2.3 days;The commonest complication was post-operative fever. CONCLUSIONS: LAVH patients have a quick postoperative recovery with less pain at the expense of a long duration of surgery. LAVH is a feasible option in a selected group of patients who would otherwise require an abdominal hysterectomy.

Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix.

To identify novel cellular genes that could potentially act as predictive molecular markers for human cervical cancer, we employed RT--PCR differential display, reverse Northern and Northern blot analysis to compare the gene expression profiles between squamous cell carcinoma biopsies and adjacent histo-pathological normal epithelium tissues. Twenty-eight cDNA clones were isolated that were demonstrated to be consistently over-expressed in squamous cell cervical cancer biopsies of FIGO stages 1B to 3B. Most importantly, it was observed that, in addition to their over-expression in cancer lesions, some of these genes are upregulated in the presumably histo-pathological normal adjacent tissues. Of particular interest is clone G30CC that has been identified to be the gene that encodes S12 ribosomal protein. When employed for RNA--RNA in situ hybridization experiments, expression of G30CC could be detected in the immature basal epithelial cells of histo-pathological normal tissues collected from cervical cancer patients of early FIGO stages. In comparison, the expression of G30CC was not detected in cervical tissues collected from patients admitted for surgery of non-malignant conditions. These results allow the distinct possibility of employing the ribosomal protein S12 gene as an early molecular diagnostic identifier for the screening of human cervical cancer and a potential target employed for cancer gene therapy trials.

Identification and characterization of genes involved in the carcinogenesis of human squamous cell cervical carcinoma.

We utilized RT-PCR differential display and cDNA microarrays to identify cellular genes involved in the multi-step carcinogenesis of squamous cell cervical carcinoma. Thirty-eight cervical cancer patients in various stages of the disease and 5 non-cervical cancer patients were studied. Twenty-five cDNA clones were identified and these were subsequently demonstrated to be consistently over-expressed in squamous cell cervical carcinoma biopsies of various FIGO stages. To further evaluate the possible role that these genes may play in the progression of disease, we performed Northern blot analysis and RNA-RNA in situ hybridization studies using cervical cancer biopsies of various FIGO stages. Of particular interest are the 2 clones G32C4B and G30CC that have been identified to be the NADH dehydrogenase 4 gene and the gene that encodes ribosomal protein S12 respectively when compared to sequences available in the GenBank database. Increased expression of these 2 genes were detected in the matched normal tissues collected together with the late FIGO stages of cervical cancer biopsies. In comparison, upregulation of these 2 genes was not detected in cervical squamous epithelium collected from patients admitted for surgery for non-malignant conditions, suggesting that expression of these 2 genes may have altered in the adjacent histopathologically "normal" cervical squamous epithelial tissue from cervical cancer patients. The ribosomal protein S12 and the NADH dehydrogenase 4 genes may therefore be potentially useful as early pre-transformation diagnostic markers for human cervical cancer.

Occupational risk for male infertility: a case-control study of 218 infertile and 227 fertile men.

The aim of the study was to determine if certain occupations pose an increased risk for infertility (of no known cause) among a group of infertile men compared with a group of fertile men. A total of 640 consecutive men whose spouses were unable to conceive were recruited from an infertility clinic. Of these, 218 men (cases) were found to have no known cause for their infertility. A total of 227 men whose spouses were pregnant at the time of the study were recruited as controls. The Singapore Standard Occupational Classification was used to code the subjects' occupations. Semen parameters (density, total sperm counts, motility, viability, and normal morphology) in all of the cases were significantly poorer than those in the controls. The risk for infertility is associated with smoking adjusted odds ratio (OR) 2.85 and 95% confidence interval (CI) 1.91 to 4.24. Work, independently, is not a risk factor for infertility. Engineering technicians (adjusted OR, 2.75; 95% CI, 1.36 to 5.54), finance analysts (adjusted OR, 4.66; 95% CI, 1.90 to 11.40), corporate and computing managers (adjusted OR, 2.49; 95% CI, 1.04 to 5.98), and teachers (adjusted OR, 7.72; 95% CI, 1.86 to 32.10) were at a greater risk of infertility compared with "services and clerical workers." Using services and clerical workers as a reference group, certain occupations are at a higher risk for infertility. Higher work demands and possible electromagnetic field exposure could be contributory factors for infertility.

Diagnosing and prognosticating acute meningitis in young infants within 24 hours of admission.

INTRODUCTION: The early diagnosis and prognosis of acute meningitis in young infants (infants 90 days old or younger) have not been well studied. We therefore investigated the diagnostic and prognostic factors for acute meningitis obtainable within 24 hours of admission. METHODS: Data were obtained through a retrospective case review of 55 young infants from 1991 to 1999 inclusive. RESULTS: The 3 commonest symptoms of acute meningitis were fever, abnormal activity and decreased feeding. The 3 commonest signs were temperature > 38.0 degrees C, irritability/crying and abnormal tone/reflexes. The best predictor of acute bacterial meningitis (ABM) was the cerebrospinal fluid (CSF)-to-blood glucose ratio. A glucose ratio of < or = 0.8 can be used to diagnose ABM with 100% sensitivity and 100% negative predictive value. Furthermore, a ratio < or = 0.3 can be used to diagnose ABM with 100% specificity and 100% positive predictive value. The best predictor of unfavourable neurological outcome (UFNO) was also the CSF-to-blood glucose ratio. A glucose ratio of < or = 0.3 again can be used to prognosticate for UFNO with 100% sensitivity and 100% negative predictive value. CONCLUSIONS: Diagnosis of acute meningitis by history and physical examination alone is difficult. However, with the aid of laboratory tests, in particular the CSF-to-blood glucose ratio, one can diagnose ABM and prognosticate for unfavourable neurological outcome with high sensitivity and high negative predictive value within 24 hours of admission.