Improvement in quality of life among Sri Lankan patients with haemorrhoids after invasive treatment: a longitudinal observational study.

BACKGROUND: Haemorrhoids is a common chronic disease that can significantly impact patients' quality of life. Yet, few studies have evaluated health-related quality of life (HRQoL) of patients with haemorrhoids before and after treatment. This study investigated the HRQoL of patients with haemorrhoids before and after treatment and the change in HRQoL from baseline. METHODS: A prospective observational study of patients with haemorrhoids was conducted at two public hospitals in Kandy, Sri Lanka. Two questionnaires assessing symptom severity and haemorrhoid-specific QoL were administered at initial consultation and at 4- and 8-week follow-ups after treatment (sclerotherapy, rubber band ligation (RBL), haemorrhoidectomy or evacuation of haematoma). The primary outcome was the least squares (LS) change of HRQoL score from baseline, measured using the Short Health Scale adapted for Haemorrhoidal Disease (4 domains: symptom load, interference with daily activities, concern, general well-being). RESULTS: In 48 patients selected for this study, LS mean change from baseline showed significant improvement in HRQoL across all domains and total Short Health Scale adapted for Haemorrhoidal Disease score at 4- and 8-week follow-ups (P < 0.001). Difference in LS mean change from baseline also showed continued improvement of HRQoL from week 4 to week 8 (P < 0.010). 'Concern' showed greatest improvement at 4 and 8 weeks (P < 0.001). Averaged LS mean changes from baseline showed RBL had greater improvement of HRQoL compared with sclerotherapy (P = 0.004). CONCLUSION: Patients with haemorrhoids had improved HRQoL after invasive treatment. Haemorrhoid-specific QoL is an important component of the extent of disease and can serve as an aid to guide treatment, assess outcomes and monitor disease.

Off-axis electron holography of Néel-type skyrmions in multilayers of heavy metals and ferromagnets.

Magnetic skyrmions are complex swirling spin structures that are of interest for applications in energy-efficient memories and logic technologies. Multilayers of heavy metals and ferromagnets have been shown to host magnetic skyrmions at room temperature. Lorentz transmission electron microscopy is often used to study magnetic domain structures in multilayer samples using mainly Fresnel defocus imaging. Here, off-axis electron holography is used to obtain in-focus electron optical phase images of Néel-type domains and skyrmions in an Ir/Fe/Co/Pt multilayer sample. The preparation of the sample, reconstruction of the holograms and influence of sample tilt angle on the signal-to-noise ratio in the phase images are discussed. A good agreement is found between images of individual skyrmions that are stabilized using an external magnetic field and simulated images based on theoretical models of Néel-type skyrmions.

A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy.

BACKGROUND: Human corneal stromal keratocytes propagated in culture media supplemented with human amnion extract (AME) can correct early corneal haze in an animal model. Clinical application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in humans. It remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation, and which components of the extract promote keratocyte growth. METHODS: Three placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein extraction. AME protein profiles were studied using isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics. Enriched gene ontology (GO) terms and functional classes were identified. Primary human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME (F-AME) or cryopreserved AME (C-AME). Cell viability, proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow cytometry. RESULTS: AME proteomics revealed 1385 proteins with similar expression levels (between 0.5- and 2-fold) between F- and C-AME, while 286 proteins were reduced (less than 0.5-fold) in C-AME. Enriched GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism, epithelial-mesenchymal transition, focal adhesion, cell-extracellular matrix interaction, cell stress regulation and complement cascades. Human corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability, while cell proliferation was mildly suppressed with C-AME (P > 0.05). Expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and CD34 was similar in both cultures. CONCLUSION: AME from cryopreserved amnion had limited influence on keratocyte culture. It is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translational applications.

Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking.

Ameloblastoma is a rare tumor of odontogenic epithelium, the low incidence rate of which precludes statistical determination of its molecular characterizations. Despite recent genomic and transcriptomic profiling, the etiology of ameloblastomas remains poorly understood. Risk factors of ameloblastoma development are also largely unknown. Whole exome sequencing was performed on 11 mandibular ameloblastoma samples. We identified 2 convergent mutational signatures in ameloblastoma: 1) a signature found in multiple types of lung cancers with probable etiology of tobacco carcinogens (COSMIC signature 4) and 2) a signature present in gingivobuccal oral squamous cell carcinoma and correlated with tobacco-chewing habits (COSMIC signature 29). These mutational signatures highlight tobacco usage or related mutagens as one possible risk factor of ameloblastoma, since the association of BRAF mutations and smoking was demonstrated in multiple studies. In addition to BRAF hotspot mutations (V600E), we observed clear inter- and intratumor heterogeneities. Interestingly, prior to BRAF mutation, important genes regulating odontogenesis mutated (e.g., corepressor BCOR), possibly playing important roles in tumorigenesis. Furthermore, recurrent mutations in the CDC73 gene, the germline mutations of which predispose patients to the development of jaw tumors, were found in 2 patients, which may lead to recurrence if not targeted by therapeutic drugs. Our unbiased profiling of coding regions of ameloblastoma genomes provides insights to the possible etiology of mandibular ameloblastoma and highlights potential disease risk factors for screening and prevention, especially for Asian patients. Because of the limited sample size and incomplete habitual, dietary, and occupational data, a causal link between tobacco usage and ameloblastoma still requires further investigations.

Influenza A(H1N1)pdm09 infection in pregnant and non-pregnant women hospitalized in Singapore, May - December 2009.

OBJECTIVES: The aim of this study was to compare the demographic and clinical characteristics of pregnant women and non-pregnant women of childbearing age hospitalized with laboratory-confirmed influenza A(H1N1)pdm09 infection in Singapore, and to assess whether pregnancy was a risk factor associated with the development of influenza-related complications. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively identified and collected information from available medical records of all women admitted to three tertiary hospitals between 26 May 2009 and 31 December 2009 with laboratory-confirmed influenza A(H1N1)pdm09 infection who were either pregnant or non-pregnant and of childbearing age between 15 and 50 years. RESULTS: A total of 222 women, of whom 81 (36.5%) were pregnant, were hospitalized during the study period. Pregnant women were significantly more likely to be hospitalized with influenza A(H1N1)pdm09 infection than non-pregnant women of childbearing age (relative risk 26.3; 95% confidence interval: 20.1-34.6). Among those hospitalized, the proportion of pregnant women having at least one underlying medical condition that could predispose them to influenza-related complications was significantly lower than that of non-pregnant women (32.1% versus 56.0%, P < 0.001). The median time from onset of symptoms to administration of anti-viral drugs was significantly shorter among pregnant women than among non-pregnant women (three days versus five days, P < 0.001). The median length of stay in hospital was also significantly shorter among pregnant women than that of non-pregnant women (two days versus three days, P = 0.002). About 4.9% of pregnant women developed influenza-related complications, compared with 12.8% among non-pregnant women (P = 0.066). CONCLUSIONS: Pregnant women with influenza A(H1N1)pdm09 infection were at a higher risk of hospitalization. Upon hospitalization, they were not at a higher risk of developing influenza-related complications.

Severe hypoglycaemia in type 1 diabetes mellitus: underlying drivers and potential strategies for successful prevention.

Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long-duration diabetes and is one of the most feared diabetes-related complications. In this review, we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia-associated autonomic failure, psychosocial and behavioural factors and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed, yet there is little randomized controlled trial evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, as well as frequency and severity of all hypoglycaemic episodes.

Lateral displacement induced disorder in L1(0)-FePt nanostructures by ion-implantation.

Ion implantation is a promising technique for fabricating high density bit patterned media (BPM) as it may eliminate the requirement of disk planarization. However, there has not been any notable study on the impact of implantation on BPM fabrication of FePt, particularly at nano-scale, where the lateral straggle of implanted ions may become comparable to the feature size. In this work, implantation of antimony ions in patterned and unpatterned L1(0)-FePt thin films has been investigated. Unpatterned films implanted with high fluence of antimony exhibited reduced out-of-plane coercivity and change of magnetic anisotropy from perpendicular direction to film-plane. Interestingly, for samples implanted through patterned masks, the perpendicular anisotropy in the unimplanted region was also lost. This noteworthy observation can be attributed to the displacement of Fe and Pt atoms from the implantation sites to the unimplanted areas, thereby causing a phase disorder transformation from L1(0) to A1 FePt.

The impact of hypoglycaemia on patients admitted to hospital with medical emergencies.

AIMS: To quantify the frequency of biochemical hypoglycaemia in acutely unwell patients in the medical assessment unit and relate this to their subsequent outcomes. METHODS: A retrospective audit was conducted on all emergency medical patients attending the medical assessment unit between November 2010 and April 2011. Capillary blood glucose measurements were obtained and electronically stored for all patients. Admission details, presence of diabetes, type of diabetes and treatment, length of stay in hospital and death in hospital were obtained from the hospital clinical coding data and electronic discharge summary. The incidence of hypoglycaemia in patients with and without diabetes was quantified. The mean age, length of stay and percentage of death in hospital were compared between groups with and without hypoglycaemia. RESULTS: One hundred and thirty-eight (9.5%) patients with diabetes and 70 (2.7%) patients without diabetes had an episode of hypoglycaemia in the medical assessment unit. Patients with diabetes and hypoglycaemia on admission had a significantly longer length of stay (mean ± sd) (10.3 ± 11.2 vs. 7.3 ± 9.5 days, P = 0.001) and higher rate of hospital mortality (14.5 vs. 5.2%, P < 0.001) compared with those without hypoglycaemia. Patients without diabetes with hypoglycaemia had a longer length of stay (mean ± sd) (9.1 ± 10.5 vs. 6.7 ± 9.9 days, P = 0.05) and a higher rate of hospital mortality (24.3 vs. 5.4%, P < 0.001) compared with those without hypoglycaemia. CONCLUSION: Hypoglycaemia is associated with an increased length of stay in hospital and an increased in-hospital mortality rate. Hypoglycaemia may have contributed to the poorer outcome, but would also appear to be a marker of disease severity in unwell patients, especially patients with sepsis.

A review of the burden of disease due to otitis media in the Asia-Pacific.

OBJECTIVE: The burden of disease due to otitis media (OM) in Asia Pacific countries was reviewed to increase awareness and raise understanding within the region. METHODS: Published literature and unpublished studies were reviewed. RESULTS: In school-age children, OM prevalence varied between 3.25% (Thailand) and 12.23% (Philippines) being highest (42%) in Aboriginal Australian children. OME prevalence at school age varied between 1.14% (Thailand) and 13.8% (Malaysia). Higher prevalence was reported in children with hearing impairment, HIV, pneumonia and rhinitis. CSOM prevalence was 5.4% in Indonesia (all ages), 15% in Aboriginal Australian children and 2-4% in Thailand, Philippines, Malaysia and Vietnam (WHO estimate). OM prevalence/incidence and service utilisation were highest in children 2-5 years of age. The disease burden was substantially higher in Pacific Island children living in New Zealand (25.4% with OME), and was highest in indigenous Australians (>90% with any OM). Streptococcus pneumoniae and Haemophilus influenzae dominated as primary causes of AOM in all studies. Few studies examined pneumococcal serotype distribution. Health-related cost estimates for OM, when available, were substantial. In developing countries, significant investment is needed to provide facilities for detection and treatment of ear disease in children, if long term hearing deficits and other sequelae are to be prevented. CONCLUSION: The available evidence suggests an important burden of disease and economic cost associated with OM in most Asia Pacific countries and a potential benefit of prevention through vaccination. Large, prospective community-based studies are needed to better define the prevalence of ear disease in children, and to predict and track pneumococcal conjugate vaccine impacts. AOM prevention through vaccination may also provide a means of reducing antibiotic use and controlling antibiotic-resistant disease in children. This review highlights the need for additional research, and provides a basis on which to build and develop regional guidelines for OM management.

Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of urinary protein in acute kidney injury.

Recent experimental and clinical studies have shown the importance of urinary proteomics in acute kidney injury (AKI). We analyzed the protein in urine of patients with clinical AKI using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) for its diagnostic value, and followed them up for 40 months to evaluate prognosis. Urine from 31 consecutive cases of AKI was analyzed with SDS-PAGE to determine the low, middle and high molecular weight proteins. Fractional excretion of sodium (FENa) was estimated from serum and urine creatinine and sodium (Na). The cases were followed-up for 40 months from the end of the recruitment of study cases. Glomerular protein was higher in the hematuria group when compared with the non-hematuria group (P <0.04) and in the AKI group than in the acute on chronic renal failure (AKI-on-CRF) group (P <0.002). Tubular protein was higher in the AKI-on-CRF group (P <0.003) than in the AKI group. Tubular protein correlated with FENa in groups with diabetes mellitus (DM), AKI-on-CRF, and without hematuria (P <0.03, P <0.02 and P <0.004, respectively). Pattern of protein did not differ between groups with and without DM and clinical acute tubular necrosis (ATN). At the end of 40 months follow-up, category with predominantly glomerular protein progressed to chronic renal failure (CRF) or end-stage renal failure in higher proportion (P <0.05). In clinical AKI, we observed that glomerular protein dominated in cases with glomerular insult, as indicated by hematuria. Tubular protein was common in the study cases with CRF, DM and cases without hematuria. This indicates tubulo-interstitial injury for AKI in these cases. Patients with predominantly glomerular protein had an adverse outcome.

Management and outcome of head and neck squamous cell carcinomas in obese patients.

Head and neck squamous cell carcinomas are common lesions, related to chronic smoking and drinking behaviors. But in contrast to other cancers, effect of obesity on occurrence, diagnosis, treatment and prognosis of these tumors remains to date unknown. This is a retrospective review of 111 obese patients (sex ratio=6.4, median age=54.5 year old), treated between 1999 and 2007. Risk factors, tumoral localization and staging (41% stage I-II) were the same as in general population. However, we found 26.1% difficult pan-endoscopies, 54% ACE-27 comorbidity scores ≥2 and 22.5% misstaged cervical lymphadenopathy. Treatment was based upon surgery (61%) or radiotherapy-chemotherapy (39%), and 37% of patients developed complications. Median follow up (38 months) and five-year overall survival (50%) are comparable to data in non obese patients. Although no direct relation between obesity and squamous cell carcinomas of the head and neck was found, obesity causes problems in tumor assessment and increases surgical complications rate. However, final good therapeutic tolerance and overall survival rate show that these patients should be managed like normal weighted ones. Receiving optimal treatments allow them to anticipate equivalent outcome as in general population.

Ministry of health clinical practice guidelines: screening of cardiovascular disease and risk factors.

The Ministry of Health (MOH) publishes clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors to provide doctors and patients in Singapore with evidence-based guidance on the screening of cardiovascular disease and risk factors. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors, for the information of readers of the Singapore Medical Journal. Page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25776). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study.

BACKGROUND: Proteinuria is an important complication in renal transplant recipients. The aim of this prospective study was to evaluate the long-term impact of transplant proteinuria patterns on allograft function and survival. METHODS: We analyzed urinary protein of a cohort of 83 renal transplants with proteinuria ≥0.5 g/d by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radial immunogel diffusion assay. After initial stratification and analysis, the cohort was followed up for 16 yr. The graft outcome and survival were analyzed using Cox regression model to determine their association with different patterns of initial transplant proteinuria. RESULTS: Group with predominantly glomerular (middle- and high-molecular-weight with or without low-molecular-weight) proteinuria (61%) had higher serum creatinine (p < 0.001) than the group with predominantly tubular (low-molecular-weight) proteinuria (39%). The incidences of chronic graft dysfunction and graft loss had increased in the glomerular proteinuria group (p < 0.001, hazard ratio 3.6, 95% confidence interval 1.7-7.5 and p < 0.001, hazard ratio 4.9, 95% confidence interval 1.9-12.1, respectively). Patient death did not differ (p = 0.434, hazard ratio 1.5, 95% confidence interval 0.5-4.5). CONCLUSION: Proteinuria in renal transplants can be differentiated into glomerular and tubular types based on molecular weight. Glomerular proteinuria is associated with significant increase in graft dysfunction and graft loss.

Genome-wide association study of bipolar I disorder in the Han Chinese population.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, ß-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Subglottic stenosis in infants and children.

INTRODUCTION: This study aimed to examine the epidemiology and outcome of subglottic stenosis in infants and children, and to evaluate the current techniques used in its diagnosis and management at the KK Women's and Children's Hospital, Singapore. METHODS: A retrospective review and long-term follow-up was conducted in all infants and children diagnosed with subglottic stenosis between January 1997 and December 2008. RESULTS: A total of 18 patients (nine male and nine female) with a median age of 7.5 months were identified. Two patients were diagnosed with definite congenital stenosis and 16 patients with acquired stenosis. The majority had Grade I stenosis (55.6 percent), followed by Grade II (27.8 percent) and Grade III (16.7 percent). None had Grade IV stenosis. 17 patients were intubated, and seven underwent tracheostomy. The most common surgical intervention performed was microlaryngoscopy and bronchoscopy with bougie dilation. The other surgical interventions included cricoid split, laryngotracheal reconstruction and cricotracheal resection. As of December 2008, the median duration of treatment was four years, with an overall recovery rate of 66.7 percent. The successful decannulation rate was 57.1 percent. Two mortalities were reported due to reasons unrelated to subglottic stenosis. Two patients were still undergoing treatment at the time of the study, and two were lost to follow-up. CONCLUSION: Conservative management alone may be required in the majority of Grade I stenosis cases. We observed that the mean number of reconstructive procedures performed per patient increased with the increase in the severity of stenosis. Each laryngeal framework procedure has to be customised to suit the individual.