Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort.

Objectives The aim of this study was to study the relationship between immunosuppressive drug treatment and survival in patients with systemic lupus erythematosus (SLE). Methods Patients who fulfilled four or more American College of Rheumatology criteria for SLE were followed longitudinally. Clinical characteristics, use of immunosuppressive agents and mortality were reviewed. Cox regression was used to study the relationship between immunosuppressive treatment and survival, adjusted for age, sex, vascular risk factors, organ damage, the anti-phospholipid antibodies and a propensity score for the indication of individual immunosuppressive agent derived from separate regression models. Results A total of 803 SLE patients were studied (92% women; age of SLE onset 33.2±14 years; follow-up time 10.8±7.7 years). The frequencies of ever use of immunosuppressive agents were: high-dose prednisolone (≥0.6 mg/kg/day for ≥4 weeks) (85%), azathioprine (63%), cyclophosphamide (25%), mycophenolate mofetil (27%), the calcineurin inhibitors (23%) and hydroxychloroquine (69%). Ninety-seven patients (12%) died and 56 (7%) patients were lost to follow-up. The causes of death were infection (44%), cerebrovascular events (12%), cardiovascular events (10%) and malignancy (8.2%). Cox regression revealed that the ever use of high-dose prednisolone, mycophenolate mofetil, calcineurin inhibitors or cyclophosphamide was not significantly associated with improved survival. However, the ever use of hydroxychloroquine (hazard ratio 0.59 (0.37-0.93); P=0.02) and azathioprine (hazard ratio 0.46 (0.28-0.75); P=0.002) was significantly associated with reduced mortality (41% and 54%, respectively) after adjustment for the propensity score and other confounding factors. A similar beneficial effect of hydroxychloroquine and azathioprine on survival was also observed in patients with lupus nephritis. Conclusions In this longitudinal cohort of Chinese SLE patients, the ever use of hydroxychloroquine and azathioprine was significantly associated with a probability of better survival. Treatment with high-dose prednisolone, cyclophosphamide, mycophenolate mofetil or the calcineurin inhibitors was not associated with long-term survival benefit.

Patient opinion of lower urinary tract symptoms and their treatment: a cross-sectional survey in Hong Kong public urology clinics.

INTRODUCTION: Lower urinary tract symptoms collectively represent a common condition among ageing men. There are, however, limited data on the frequency of individual symptoms in patients who seek specialist care. We conducted a multinational survey in South-East Asia to evaluate patients' self-reported prevalence, bother, treatment, and treatment satisfaction of four lower urinary tract symptoms namely, urgency, nocturia, slow stream, and post-micturition dribble. This report presents the analysis of the Hong Kong subpopulation. METHODS: This cross-sectional survey involved adult men aged over 18 years who attended a urology out-patient clinic because of lower urinary tract symptoms. A structured questionnaire, translated and validated in the local languages, was self-administered by patients. RESULTS: Of 1436 respondents surveyed in the region, 225 were from Hong Kong of whom most were aged 56 to 75 years, retired, and had no history of any previous prostate surgery. Overall, the self-reported prevalence of nocturia of at least one void per night was 93% (95% confidence interval, 90%-97%), slow stream 76% (71%-82%), post-micturition dribble 70% (64%-76%), and urgency 50% (43%-56%). Symptoms for which most respondents reported "some" or "a lot" of bother included: nocturia, defined as at least two voids per night (77%), and urgency and post-micturition dribble (73%). Only 39% to 54% of patients had previously received treatment but were not entirely satisfied with it. An understanding of their condition remained suboptimal. CONCLUSIONS: In Hong Kong, nocturia emerged as the most prevalent and one of the most bothersome symptoms among men who sought urologist care for lower urinary tract symptoms. Compared with the non-Hong Kong population, Hong Kong respondents tended to be highly symptomatic and bothered. They were, however, less likely to have received treatment and were generally less satisfied with previous treatment.

Participant evaluation of simulation training using crew resource management in a hospital setting in Hong Kong.

INTRODUCTION: A simulation team-based crew resource management training programme was developed to provide a unique multidisciplinary learning experience for health care professionals in a regional hospital in Hong Kong. In this study, we evaluated how health care professionals perceive the programme. METHODS: A cross-sectional questionnaire survey was conducted in the Multidisciplinary Simulation and Skills Centre at Queen Elizabeth Hospital in Hong Kong. A total of 55 individuals in the departments of Obstetrics and Gynaecology, Anaesthesiology and Operating Theatre Services, Intensive Care Unit, and Accident and Emergency participated in the study between June 2013 and December 2013. The course content was specially designed according to the needs of the clinical departments and comprised a lecture followed by scenarios and debriefing sessions. Principles of crew resource management were introduced and taught throughout the course by trained instructors. Upon completion of each course, the participants were surveyed using a 5-point Likert scale and open-ended questions. RESULTS: The participant's responses to the survey were related to course organisation and satisfaction, realism, debriefing, and relevance to practice. The overall rating of the training programme was high, with mean Likert scale scores of 4.1 to 4.3. The key learning points were identified as closed-loop communication skills, assertiveness, decision making, and situational awareness. CONCLUSIONS: The use of a crew resource management simulation-based training programme is a valuable teaching tool for frontline health care staff. Concepts of crew resource management were relevant to clinical practice. It is a highly rated training programme and our results support its broader application in Hong Kong.

Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial.

OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.

Long-term outcome of rheumatoid arthritis defined according to the 2010-classification criteria.

OBJECTIVE: The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been thoroughly studied for the test characteristics but it is unclear whether '2010 RA' has a different phenotype than '1987 RA' when assessing the severity of the disease course. Therefore this study compared two long-term disease outcomes. METHODS: 1502 early arthritis patients that had no other diagnoses than RA or undifferentiated arthritis (UA) were studied on fulfilling the 1987 ACR criteria, 2010 criteria or both. The severity of joint damage was studied with yearly radiographs over 7 years. Achieving disease-modifying anti-rheumatic drug (DMARD)-free sustained remission was assessed over 10-years follow-up. Multivariate normal regression and Cox-proportional hazard regression were used, adjusting for age, gender and treatment. RESULTS: 550 patients fulfilled the 1987 criteria, 788 patients the 2010 criteria and 489 both criteria sets. Patients fulfilling the 2010 criteria developed less severe radiological joint damage (p=0.023) and achieved DMARD-free sustained remission more often (HR=1.18 (0.93-1.50)) than patients fulfilling the 1987 criteria, though the latter was not statistically significant. All 1987+2010- patients were anti-citrullinated peptide antibody (ACPA)-negative. When also applying the radiologic criterion of the 2010-criteria, half of the 1987+2010- patients became 2010 criteria positive, but results on the long-term outcome remained similar. CONCLUSIONS: '2010 RA' has a milder disease course than '1987 RA'. This may have important implications for basic scientific studies and clinical trials in RA.

Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: a 12-month prospective study.

OBJECTIVE: The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy. METHODS: Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥ 2 immunosuppressive regimens. While prednisolone (≤ 10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months. RESULTS: Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V+III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal. CONCLUSIONS: Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.

Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus: a comparison with anti-dsDNA and anti-C1q.

OBJECTIVES: To study the sensitivity and specificity of vitamin D deficiency for predicting disease activity and damage of systemic lupus erythematosus (SLE) in comparison with anti-dsDNA and anti-C1q. METHODS: Consecutive patients who fulfilled four or more ACR criteria for SLE were studied. Levels of 25-hydroxyvitamin D3, anti-C1q, anti-dsDNA and complement levels were measured. Relationship among these markers, concurrent disease activity and damage scores of SLE was studied by Spearman's rank correlation method. RESULTS: In total, 290 SLE patients were studied (95% women; mean age 38.9 ± 13.1 years; SLE duration 7.7 ± 6.7 years). Clinical or serological lupus activity (SLEDAI ≥ 1) was present in 225 (78%) patients. Vitamin D deficiency (< 15 ng/ml) was detected in 78 (27%) patients. Levels of 25-hydroxyvitamin D3 correlated inversely with the clinical SLE disease activity score (Rho = -0.26; p < 0.001). A negative correlation was also observed between 25-hydroxyvitamin D3 and anti-dsDNA levels (Rho = -0.13; p = 0.02), or anti-C1q (Rho = -0.14; p = 0.02). However, there was no significant relationship between levels of 25-hydroxyvitamin D3 and complement C3 (Rho = 0.09; p = 0.12) or C4 (Rho = 0.09; p = 0.13). Both 25-hydroxyvitamin D3 deficiency and anti-C1q were more specific but less sensitive than anti-dsDNA for concurrent clinical renal and non-renal SLE activity. Levels of 25-hydroxyvitamin D3, anti-dsDNA or anti-C1q did not correlate significantly with the SLE damage scores. CONCLUSIONS: 25-hydroxyvitamin D3 correlated inversely and significantly with clinical SLE activity, anti-C1q and anti-dsDNA titers, but not with complement levels or damage scores. Deficiency of 25-hydroxyvitamin D3 was as specific as anti-C1q, but less sensitive than anti-dsDNA, for detecting concurrent renal and non-renal clinical activity of SLE.

Life expectancy, standardized mortality ratios, and causes of death in six rheumatic diseases in Hong Kong, China.

OBJECTIVE: To examine the life expectancy, standardized mortality ratios (SMRs), and causes of death in 6 groups of patients from Hong Kong with different rheumatic diseases. METHODS: Patients with a diagnosis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic vasculitis (SV), or systemic sclerosis (SSc) registered in 37 public hospitals between 1999 and 2008 were identified in the hospital registry. SMRs were calculated by comparing the mortality rate in patients with each disease with that in the general population. Life expectancy was calculated by abridged life-table analysis, and the causes of death were compared. RESULTS: In 2008, data on 8,367 RA, 5,243 SLE, 2,154 AS, 1,636 SV, 778 PsA, and 449 SSc patients were available in our registry. The age- and sex-adjusted SMRs were highest for SLE (5.25 [95% confidence interval 4.79-5.70]), SSc (3.94 [95% confidence interval 3.20-4.68]), and SV (2.64 [95% confidence interval 2.36-2.93]). In female patients, the loss in life expectancy was greatest for SSc (34.1 years), SV (19.3 years), and SLE (19.7 years). In male patients, the loss in life expectancy was highest for SV (28.3 years), SLE (27 years), and SSc (16 years). There were 2,486 deaths during the study period (1999-2008), and the principal causes were infections (28%), cardiovascular complications (18%), cancer (16%), and disease activity (7%). Infection was the leading cause of death in SLE, RA, AS, and PsA, whereas deaths from disease-related activity and cardiovascular complications were most frequent in SSc. Cancer was the most common cause of death in SV. CONCLUSION: Our findings indicate that patients with SLE, RA, AS, PsA, SV, and SSc have increased mortality rates and reduced life expectancy. SLE has the highest adjusted SMR, and female SSc patients have the greatest loss in life expectancy. Infection is the leading cause of death, followed by cardiovascular complications and malignancies.

A systematic review of nudge theories and strategies used to influence adult health behaviour and outcome in diabetes management.

BACKGROUND: Diabetes is a chronic disease associated with a variety of complications, and nudging may be a potential solution to improve diabetes control. Since nudging is a new concept, no review of literature on nudging diabetic patients into improving their health behaviour has been done. Therefore, we aim to collate a list of nudge intervention and determine the context in which nudging is successful. METHODS: We adopted a two-arm search strategy comprising the search of literature databases and snowballing using relevant search terms. We summarized patient characteristics, the nudge intervention, according to nudging strategies, delivery mode and their outcomes. The conditions present in effective nudge interventions were assessed and reported. RESULTS: We retrieved 11,494 studies from our searches and included 33. An additional five studies were added through snowballing. Studies included utilized framing (n=5), reminders (n=10), gamification (n=2), social modelling (n=5) and social influence (n=16). Studies on reminders and gamification were more likely to have a statistically significant outcome. The targeted health behaviours identified were medication adherence, physical activity, diet, blood glucose monitoring, foot care, self-efficacy, HbA1c and quality of life. Of these, studies with adherence to medication, foot care practice and quality of life as targeted health behaviours were more likely to show a statistically significant outcome. CONCLUSION: Nudging has shown potential in changing health behaviour of patients with diabetes in specific context. We identified two possible factors (delivery mode and patient characteristics) that may affect the effectiveness of nudge intervention.

Annual incidence and standardized incidence ratio of cerebrovascular accidents in patients with systemic lupus erythematosus.

OBJECTIVES: To study the annual incidence and standardized incidence ratio (SIR) of cerebrovascular accident (CVA) in patients with systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: The annual incidence of CVA from 1999 to 2007 in a longitudinal cohort of SLE patients was calculated each year and compared with that of the regional population within the same study period. Age-specific SIRs and outcome of CVA in SLE patients were also studied. RESULTS: In 2007, there were 490 SLE patients in our cohort. The mean annual incidence of CVA between 1999 and 2007 was 6.45/1000 patients and no obvious trend over time was observed. Of the 20 CVAs in patients with SLE, 18 (90%) were ischaemic stroke whereas two (10%) were haemorrhagic stroke. The mean SIR of all types of CVA in SLE patients was 2.02 [95% confidence interval (CI) 1.30-3.81; p = 0.002]. The SIR of ischaemic stroke decreased with age and the stroke incidence was no longer significantly higher than that of the population in patients aged >or= 60 years. Haemorrhagic stroke occurred mainly in younger SLE patients. The duration of hospitalization and the mortality rate for CVA was non-significantly higher in SLE than in non-SLE patients. CONCLUSIONS: The incidence of CVA in SLE remained constant over the 8 years between 1999 and 2007. Younger SLE patients are at substantially increased risk of CVA compared to age-matched population. The duration of hospitalization and the mortality rate for CVA are similar in SLE and non-SLE patients.

Effect of disease activity and damage on quality of life in patients with systemic lupus erythematosus: a 2-year prospective study.

OBJECTIVES: To examine the effect of disease activity and damage on health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients and matched controls were recruited for a study of HRQoL using the Medical Outcomes Study Short Form-36 (SF-36). SLE activity and damage was assessed by the Safety of Oestrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) and the American College of Rheumatology/Systemic Lupus International Collaborating Clinics (ACR/SLICC) Damage Index (SDI), respectively. Patients were prospectively followed for repeat HRQoL assessment at 2 years. The effects of cumulative disease activity and new damage on changes in SF-36 scores were evaluated. RESULTS: One hundred and fifty-five patients were studied (94% women; age 37.8+/-11.3 years; SLE duration 7.2+/-5.4 years). Fifty (32%) patients had active disease and 75 (48%) had organ damage at baseline. Compared with age- and gender-matched controls, SLE patients had lower SF-36 scores, and the difference remained significant after adjustment for income and education level. SF-36 scores in SLE patients correlated inversely with SDI but not with SELENA-SLEDAI scores. After 2 years, there was a significant drop in the mental component score of the SF-36. Regression analysis revealed that new damage was the only determinant for a reduction in SF-36 scores. Patients with higher cumulative disease activity had a greater drop in bodily pain and general health subscores. CONCLUSIONS: Impaired HRQoL is more common in SLE patients than controls, regardless of age, sex, education and poverty. Pre-existing organ damage is associated with poorer HRQoL and new damage predicts a further decline in HRQoL. Persistent disease activity is associated with deterioration in certain domains of the SF-36.

Polyhydroxyalkanoates production from carbohydrates by a genetic recombinant Aeromonas sp.

AIMS: To develop an Aeromonas strain able to utilize inexpensive carbon sources such as starch for the synthesis of polyhydroxyalkanoates (PHA). METHODS AND RESULTS: A recombinant Aeromonas sp. (strain KC007-1) was constructed by introducing the PHB synthesis genes (phaCAB) into the bacterium. Strain KC001-R1 can not only use carbohydrate (including starch) for growth but also accumulate significant amounts of polyhydroxybutyrate (PHB) in the cells. CONCLUSIONS: One of the present focuses on PHA production has been on lowering the production costs. Starch is an example of an inexpensive carbohydrate for use in industrial production of PHA. We have demonstrated that by introducing the phaCAB operon into Aeromonas sp. allowed the bacterium able to accumulated PHB using this substrate. SIGNIFICANCE AND IMPACT OF THE STUDY: Aeromonas spp. are able to synthesize PHA using fatty acids as carbon source. Although good robust growth results with use of starch as sole carbon source for Aeromonas, PHA synthesis does not occur. Strain KC007-R1 showed the ability to accumulate PHA in relative high amount with both carbohydrates and fatty acids as carbon source, and can be cultivated to a significant amount of cell mass and hence is a potential strain for further development for industrial applications.

Long-term immunogenicity of a quadrivalent human papillomavirus vaccine in systemic lupus erythematosus.

OBJECTIVES: To evaluate the 5-year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE). METHODS: Female SLE patients and controls, aged 18-35 years, who received GARDASIL in 2011 and sero-converted 12 months post-vaccination were followed for persistence of immunogenicity. Antibody measurement to HPV serotypes 6, 11, 16, 18 was repeated at 5 years. The rate of sero-reversion was compared between patients and controls, and factors associated with sero-reversion of the anti-HPV antibodies were studied. RESULTS: 50 SLE patients and 50 controls were vaccinated with GARDASIL. Among subjects who sero-converted at 1 year and consented for this study, antibodies to HPV serotypes 6, 11, 16 and 18 at 5 years were persistent in 24/27 (89%), 26/31 (84%), 32/34 (94%) and 24/25 (96%) of the SLE patients; and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Antibody titers to HPV-6 and 16 were significantly lower in patients than controls. Seven (21%) SLE patients had sero-reversion of ≥1 anti-HPV antibodies. Sero-reverted patients experienced significantly more SLE flares, particularly renal, and had received significantly higher cumulative doses of prednisolone, mycophenolate mofetil and tacrolimus than those with persistent immunogenicity. The cumulative doses of prednisolone correlated inversely and significantly with the anti-HPV 6, 11, and 16 titers at 5 years. CONCLUSIONS: Immunogenicity of the quadrivalent HPV vaccine was retained in a high proportion of SLE patients at 5 year. Patients with more SLE renal flares and had received more immunosuppression were more likely to have sero-reversion of the anti-HPV antibodies. CLINICAL TRIAL REGISTRATION NUMBER: US ClinicalTrials.gov (NCT00911521 & NCT02477254).

Universal newborn hearing screening in Singapore: the need, implementation and challenges.

With about 1 in 1000 born with severe to profound hearing loss and about 5 in 1000 with lesser degrees of loss, congenital deafness is the commonest major birth defect. It is the recommended standard that hearing loss in newborns be detected by 3 months of age and intervention implemented by 6 months of age. Delayed detection and intervention may affect speech, language and psychosocial development, resulting in poor academic achievements. Universal newborn hearing screening (UNHS) is the only effective way of detecting all babies with hearing loss, within the recommended time frame. A survey in Singapore revealed that traditional childhood hearing screening programmes resulted in late detection (mean age, 20.8 months; range, 0 to 86 months) and late intervention (mean age, 42.4 months; range, 1 to 120 months). Increasingly, UNHS is becoming standard medical care in developed countries. In Singapore, UNHS has been implemented in all hospitals with obstetric services. Although a screening rate of more than 99% has been achieved in public hospitals, private hospitals have a screening rate of only about 77%. Parents' awareness and acceptance of early detection is still lacking, and this needs to be addressed by appropriate public education. Support from obstetricians and paediatricians will significantly contribute towards this objective. Effective programme management is essential; this includes the use of data management systems, the maintenance of a team of experienced screeners, and efficient coordination between screening and diagnostic services. Early detection of childhood deafness, together with early and effective intervention, maximises the chances of successful integration into mainstream education and society.

Incidence, risk factors of retinopathy of prematurity among very low birth weight infants in Singapore.

INTRODUCTION: To determine the incidence, risk factors and need for surgery for retinopathy of prematurity (ROP) among very-low-birth-weight (VLBW) infants. MATERIALS AND METHODS: This was a retrospective study of all VLBW infants managed by the department over 14 years, from 1988 to 2001. Preterm infants were examined according to the Royal College of Ophthalmologists' guidelines, and retinopathy was graded following the International Classification of ROP. All VLBW infants examined for ROP were included and data were retrieved retrospectively and analysed for maternal, medical, obstetric and neonatal risk factors using logistic regression. RESULTS: Of the 564 VLBW infants who fit the screening criteria, ROP was detected in 165 (29.2%) of VLBW infants; of whom 49% of infants had stage 1 disease, 24% were at stage 2, and 27% were at stage 3 or more. Among 45 infants with stage 3 disease or more, treatment was needed in 62.2% (28/45). No ROP was detected in infants greater than 33 weeks of gestation. Only 0.6 % (1/164) of infants greater than 30 weeks of gestational age (GA) needed surgery for ROP. Using birth weight (BW) criteria, stage 3 ROP was noted only in 1% (6/564) of infants with BW >1000 g. Of all ROP requiring surgery, 89% (25/28) of infants were <1000 g as compared to 11% (3/28) who were >1000 g infants. The median age of onset of ROP was 35 weeks (range, 31 to 41) corrected age. By univariate analysis for threshold ROP, preeclampsia, prenatal betamethasone exposure, gestational age, birth weight, 1-minute Apgar score, hyaline membrane disease (HMD), surfactant usage, hypotension, septicaemia, intraventricular haemorrhage duration of supplemental oxygen, ventilation and chronic lung disease were associated with ROP requiring surgery (i.e., threshold ROP, P <0.05). However, using multiple logistic regression analyses for ROP, maternal preeclampsia [odds ratio (OR), 2.52; confidence interval (CI), 1.32 to 4.7], birth weight (OR, 0.99; CI, 0.996 to 0.999), pulmonary haemorrhage (OR, 4.61; CI, 1.04 to 20.4), duration of ventilation (OR, 1.06; CI, 1.04 to 1.08) and duration of continuous positive airway pressure (CPAP) (OR, 1.02; CI, 1.01 to 1.04) were factors predictive of development of threshold ROP. CONCLUSION: The incidence of ROP among VLBW infants was 29.2%. ROP was strongly associated with smaller, more immature and sicker infants. The median age of onset of ROP was 35 weeks (range, 31 to 40 weeks) postmenstrual age. Infants <30 weeks of GA and/or infant with BW <1000 g are at considerable risk for threshold ROP. The main risk factors for development of threshold ROP by regression analysis are maternal preeclampsia, birth weight, and presence of pulmonary haemorrhage, duration of ventilation and continuous positive pressure ventilation. We suggest that both immaturity and compromised pulmonary function are both important aetiological factors in the development of ROP. Prevention of prematurity, control of preeclampsia, judicious use of ventilation and oxygen therapy are the only promising factors that may reduce the incidence and severity of ROP in this high-risk infant.

Tissue-limited mosaicism in Pallister-Killian syndrome -- a case in point.

We report a case of Pallister-Killian syndrome in a term female infant. Antenatal ultrasound showed left diaphragmatic hernia and polyhydramnios. She was ventilated from birth and the diaphragm defect repaired on day 5. She had dysmorphic features, including median cleft palate, patchy frontotemporal alopecia, hypopigmented skin whorls, and bilateral profound sensorineural hearing loss. Fetal and postnatal karyotypes of peripheral lymphocytes were both normal, 46, XX. Subsequently, a skin fibroblast culture showed mosaic tetrasomy of isochromosome 12p both on G-banding and fluorescence in situ hybridization, consistent with Pallister-Killian syndrome. This case illustrates the importance of using the appropriate sample type for karyotype analysis with implications for prenatal and postnatal diagnosis.

Penile length of newborns in Singapore.

Micropenis is an important sign in congenital hypopituitarism and various disorders. Documented norms for penile length exist only for babies of Caucasian and Middle-Eastern origin. This study was carried out to establish such norms for Asian newborns. We studied 228 male live births within their first three days of life. Stretched penile lengths were marked off on unmarked wooden spatulas, which were placed vertically along the dorsal aspect of the penis, with one rounded end on the pubic bone. The mean penile length +/- S.D. for the full-term Asian baby was 3.6 +/- 0.4 cm. Race had a significant effect: Chinese 3.5 cm, Malay 3.6 cm and Indian 3.8 cm. Penile length correlated with birth weight and gestational age. Asian babies thus have similar norms to Caucasian babies. An Asian newborn whose penis measures less than 2.6 cm has micropenis and may need prompt investigation for underlying endocrine disorders.

Mortality among infants with high-risk congenital diaphragmatic hernia in Singapore.

Several factors suggested to predict mortality in congenital diaphragmatic hernia (CDH) have not always been applicable in different centers. A retrospective review was conducted of 19 consecutive neonates in Singapore in whom CDH was diagnosed within 12 hours of birth to identify factors associated with mortality. Of the 19 cases, 15 (79%) were diagnosed using antenatal ultrasonography. Eight (42%) underwent primary repair at a median age of 23 hours (range, 12 to 50 hours). Of the 19 infants, 15 died (mortality rate, 79%). Survivors until hospital discharge were compared with nonsurvivors. Antenatal diagnosis and stomach position in left-sided defects had no effect on outcome, although polyhydramnios tended to be associated with nonsurvival. Significant postnatal factors associated with mortality included a low arterial pH level, low initial arterial-alveolar oxygen ratio, high initial alveolar-arterial oxygen gradient, as well as high oxygenation and ventilation indices. These results reflect difficulty in oxygenation because of pulmonary hypoplasia despite evidence of adequate ventilation. There was no difference between survivors and nonsurvivors in either their initial or best postductal blood gases. The "Bohn quadrants" did not aid in predicting survival of infants who underwent repair because all eight such infants had best postductal carbon dioxide values of less than 40 mm Hg and ventilation indices of less than 1,000. Yet only four (50%) survived until hospital discharge. Large-scale evaluation of these factors may be required in the future to demonstrate their validity and reliability because of changing management strategies for CDH.

Coupling of waste water treatment with storage polymer production.

Storage polymers in bacterial cells can be extracted and used as biodegradable thermoplastics. However, widespread applications have been limited by high production costs. In this study, activated sludge bacteria in a conventional waste water treatment system were induced, by controlling the carbon-nitrogen (C:N) ratio in the reactor liquor, to accumulate storage polymers. Specific polymer yield increased to a maximum of 0.374 g polymer/g cell when the C:N ratio was increased from from 24 to 144, whereas specific growth yield decreased with increasing C:N ratio. An optimum C:N ratio of 96 provided the highest overall polymer production yield of 0.093 g of polymer/g of carbonaceous substrate consumed, without significantly affecting the organic treatment efficiency in the waste water treatment system.