Transnasal frontal intersinus septum takedown for frontal sinus pyocele.

INTRODUCTION: The open frontal intersinus septum takedown (FISST) technique was first described in 1976. We describe our experience with an endoscopic transnasal approach to manage a frontal sinus pyocele arising from an obstructed frontal sinus outflow tract due to anterolateral thigh flap reconstruction of a maxillectomy defect. CASE REPORT: A 40-year-old lady experienced upper eyelid swelling and purulent nasal discharge 3 weeks after undergoing a left extended medial maxillectomy with free anterolateral thigh flap reconstruction. A computed tomography (CT) scan revealed total opacification of the left frontal sinus. There was no improvement with intravenous antibiotics and she underwent a surgery, whenshe was found intraoperatively to have a frontal sinus pyocele, which was then drained. She then underwent an endoscopic transnasal FISST to ventilate the left frontal sinus via the contralateral frontal recess with good results. A CT scan performed 3 months postoperatively showed a widely patent interfrontal sinus septal window and right frontal outflow tract with no disease recurrence. DISCUSSION: The FISST is a useful technique to manage unilateral frontal sinus disease by taking advantage of the contralateral outflow tract when the ipsilateral frontal recess is obstructed.

Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

Low-dissolved-oxygen nitrification in tropical sewage: an investigation on potential, performance and functional microbial community.

Intensive aeration for nitrification is a major energy consumer in sewage treatment plants (STPs). Low-dissolved-oxygen (low-DO) nitrification has the potential to lower the aeration demand. However, the applicability of low-DO nitrification in the tropical climate is not well-understood. In this study, the potential of low-DO nitrification in tropical setting was first examined using batch kinetic experiments. Subsequently, the performance of low-DO nitrification was investigated in a laboratory-scale sequential batch reactor (SBR) for 42 days using real tropical sewage. The batch kinetic experiments showed that the seed sludge has a relatively high oxygen affinity. Thus, the rate of nitrification was not significantly reduced at low DO concentrations (0.5 mg/L). During the operation of the low-DO nitrification SBR, 90% of NH4-N was removed. The active low-DO nitrification was mainly attributed to the limited biodegradable organics in the sewage. Fluorescence in-situ hybridisation and 16S rRNA amplicon sequencing revealed the nitrifiers were related to Nitrospira genus and Nitrosomonadaceae family. Phylogenetic analysis suggests 47% of the operational taxonomic units in Nitrospira genus are closely related to a comammox bacteria. This study has demonstrated active low-DO nitrification in tropical setting, which is a more sustainable process that could significantly reduce the energy footprint of STPs.

Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count.

BACKGROUND: There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count METHODS: We identified 405 patients on DMF and 300 patients on FNG (treatment duration: at least 12 month) within a large prospective study of MS patients conducted at the Partners MS Center, Brigham and Women's Hospital (CLIMB study) between Jan 2011 to Feb 2016. Patients had complete blood counts with differentials at baseline and every 6 months while on treatment. Most participants had a clinical visit with complete neurologic examinations every 6 months and brain MRI scan every 12 months. T cell subset profile was available for subgroup of patients (n = 116). RESULTS: In the FNG group, the risk of developing lymphopenia grade 4 (< 200) was higher in female patients (p = 0.0117) and those who were previously treated with natalizumab (p = 0.0116), while the risk of lymphopenia grade 3b+4 (< 350) was higher in female patients (p = 0.0009). DMF treated patients with lower baseline lymphocyte count had a higher chance of developing lymphopenia grade 2 (< 800) (p < 0.0001) or 2+3 (< 500) (p < 0.0001). We examined the effect of treatment switch between DMF and FNG. No significant recovery in lymphocyte and leukocyte count was observed after treatment switches. Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients. CONCLUSION: Female sex and prior exposure to natalizumab increased the probability of lymphopenia on FNG, while low absolute lymphocyte count was associated with increased risk of lymphopenia on DMF. Parallel switch did not lead to recovery from hematological abnormalities. Long-term studies with larger number of patients are required to confirm our findings and to establish guidelines for prediction and management of hematological abnormalities.

The role of chronic viral hepatitis on tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) drug-induced liver injury (TB-DILI) usually occurs within 8 weeks of anti-tuberculosis drug initiation. In Singapore, we suspected that the onset of TB drug-induced transaminitis may be confounded with hepatitis C virus (HCV) and hepatitis B (HBV) virus co-infection. OBJECTIVE: To determine the impact of HCV/HBV co-infection on the course of treatment in patients with TB treatment interrupted due to transaminitis. DESIGN: TB patients with treatment interruption during 2013-2014 were identified through the Singapore national TB registry. Case notes of those with transaminitis were perused. RESULTS: Of 3860 TB patients notified, 140 had suspected TB-DILI. Of these, respectively 20/140 (14.3%) and 16/140 (11.4%) were HCV- or HBV-positive. The median time to treatment interruption/transaminitis was 5 weeks vs. 9.9 weeks and 9.6 weeks for transaminitis patients without chronic liver disease and with HCV/HBV co-infection (P < 0.01). Multivariate logistic regression analysis revealed that having HCV/HBV co-infection was associated with treatment interruption occurring beyond 8 weeks (adjusted OR [aOR] 4.06, 95%CI 1.28-12.85); HCV transaminitis patients were more likely to take 10 months to complete anti-tuberculosis treatment (aOR 5.11, 95%CI 1.21-21.67) than those without chronic liver disease. CONCLUSION: TB treatment interruption due to transaminitis in HCV/HBV co-infected patients occurred later than in those without liver disease. Most had completed 2 months of pyrazinamide-containing intensive phase treatment before the onset of transaminitis.

The association between distance to public amenities and cardiovascular risk factors among lower income Singaporeans.

Existing evidence on the association between built environment and cardiovascular disease (CVD) risk factors focused on the general population, which may not generalize to higher risk subgroups such as those with lower socio-economic status (SES). We examined the associations between distance to 5 public amenities from residential housing (public polyclinic, subsidized private clinic, healthier eatery, public park and train station) and 12 CVD risk factors (physical inactivity, medical histories and unhealthy dietary habits) among a study sample of low income Singaporeans aged ≥ 40 years (N = 1972). Using data from the Singapore Heart Foundation Health Mapping Exercise 2013-2015, we performed a series of logistic mixed effect regressions, accounting for clustering of respondents in residential blocks and multiple comparisons. Each regression analysis used the minimum distance (in km) between residential housing and each public amenity as an independent continuous variable and a single risk factor as the dependent variable, controlling for demographic characteristics. Increased distance (geographical inaccessibility) to a train station was significantly associated with lower odds of participation in sports whereas greater distance to a subsidized private clinic was associated with lower odds of having high cholesterol diagnosed. Increasing distance to park was positively associated with higher odds of less vegetable and fruits consumption, deep fried food and fast food consumption in the preceding week/month, high BMI at screening and history of diabetes, albeit not achieving statistical significance. Our findings highlighted potential effects of health-promoting amenities on CVD risk factors in urban low-income setting, suggesting gaps for further investigations.

Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes.

Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19-3.91; MI, 2.10,1.17-3.76; CES-D, 3.08,1.65-5.76; AES, 2.39,1.32-4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76-0.97) and CES-D (OR, 95% CI: 0.85, 0.74-0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.

Health care provider perspectives on tuberculosis care for foreign-born populations in New York City.

BACKGROUND: Tuberculosis (TB) in foreign-born patients is a key determinant of TB epidemiology in low-burden settings. In New York City (NYC), foreign-born TB populations are heterogeneous and face diverse challenges in accessing care. OBJECTIVE: To characterize barriers and facilitators to health care services and identify potential mechanisms to improve TB care for foreign-born patients in NYC. DESIGN: Semi-structured interviews with health care providers identified through the NYC TB registry and snowball sampling. Transcripts were analyzed using a modified grounded theory approach. RESULTS: Fourteen providers from private practice (21%), community clinic (36%), and hospitals (43%) were interviewed. Barriers clustered into thematic areas: interrelated social and economic issues that impact TB care and treatment (documentation status, poverty, mental/behavioral health issues), challenges of fragmented health system (care continuity, costs), latent tuberculous infection, and relative lack of resources and significant barriers for clinic and private practice providers. Health care providers' deep commitment to foreign-born TB patients was evidenced by their attitudes and actions. CONCLUSION: Improving access to TB care for foreign-born patients in NYC requires strategies that address specific social, economic and structural barriers. Improving linkages between private providers and public health initiatives is a key challenge. Health care providers' commitment to foreign-born communities is a significant resource.

Fast methods for training Gaussian processes on large datasets.

Gaussian process regression (GPR) is a non-parametric Bayesian technique for interpolating or fitting data. The main barrier to further uptake of this powerful tool rests in the computational costs associated with the matrices which arise when dealing with large datasets. Here, we derive some simple results which we have found useful for speeding up the learning stage in the GPR algorithm, and especially for performing Bayesian model comparison between different covariance functions. We apply our techniques to both synthetic and real data and quantify the speed-up relative to using nested sampling to numerically evaluate model evidences.

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe-/- × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe-/- × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe-/- × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

Long-term performance evaluation of EBPR process in tropical climate: start-up, process stability, and the effect of operational pH and influent C:P ratio.

To date, little information is known about the operation of the enhanced biological phosphorus removal (EBPR) process in tropical climates. Along with the global concerns on nutrient pollution and the increasing array of local regulatory requirements, the applicability and compliance accountability of the EBPR process for sewage treatment in tropical climates is being evaluated. A sequencing batch reactor (SBR) inoculated with seed sludge from a conventional activated sludge (CAS) process was successfully acclimatized to EBPR conditions at 28 °C after 13 days' operation. Enrichment of Candidatus Accumulibacter phosphatis in the SBR was confirmed through fluorescence in situ hybridization (FISH). The effects of operational pH and influent C:P ratio on EBPR were then investigated. At pH 7 or pH 8, phosphorus removal rates of the EBPR processes were relatively higher when operated at C:P ratio of 3 than C:P ratio of 10, with 0.019-0.020 and 0.011-0.012 g-P/g-MLVSS•day respectively. One-year operation of the 28 °C EBPR process at C:P ratio of 3 and pH 8 demonstrated stable phosphorus removal rate of 0.020 ± 0.003 g-P/g-MLVSS•day, corresponding to effluent with phosphorus concentration <0.5 mg/L. This study provides the first evidence on good EBPR activity at relatively high temperature, indicating its applicability in a tropical climate.

Comparing the use of glycerol preserved and cryopreserved allogenic skin for the treatment of severe burns: differences in clinical outcomes and in vitro tissue viability.

Cryopreserved (CryoPA) and Glycerol-preserved (GPA) skin allografts are commonly used in the treatment of severe burn injuries. However, comparable data on their differences in clinical outcome is scarce. This retrospective review aims to study the effect of allograft viability on clinical outcomes. The records of 48 severe burn patients who either received CryoPA or GPA were reviewed. Key burn mortality determinants were used to match the 2 groups. Clinical outcomes such as mortality rate (MR) and the length of hospital stay (LOS) were obtained. A separate in vitro comparison included histological assessments and the use of tetrazolium reductase activity to compare tissue viability. Both groups showed a comparable profile in burn mortality determinants. Patients who received CryoPA had a lower MR of 25% compared to 34.8% (P=0.250) in the GPA group and a lower LOS of 39.2-45.9 days (P=0.730), respectively. The histological structural integrity was found to be well preserved with both methods although CryoPA was confirmed to be the more viable product (P<0.05). The lower MR associated with CryoPA cannot be totally ignored. However, the mechanism through which viable skin allografts improves MR of severe burns patients remains to be elucidated.

Singapore's burden of disease and injury 2004.

INTRODUCTION: The Singapore Burden of Disease (SBoD) Study 2004 provides a comprehensive and detailed assessment of the size and distribution of health problems in Singapore. It is the first local study to use disability-adjusted life years (DALYs) to quantify the total disease burden. METHODS: The SBoD study applied the methods developed for the original Global Burden of Disease study to data specific to Singapore to compute the DALYs. DALY is a summary measure of population health that combines time lost due to premature mortality (years of life lost [YLL]) with time spent in ill-health (broadly-termed disability) arising from incident cases of disease or injury (years of life lost due to disability [YLD]). DALYs, stratified by gender and age group, were calculated for more than 130 specific health conditions for the Singapore resident population for the year 2004. RESULTS: In 2004, diabetes mellitus, ischaemic heart disease and stroke were the top three leading causes of premature death and ill-health in Singapore, and together accounted for more than one-quarter (28 percent) of the total disease burden (in DALYs). Morbidity burden (YLD) was responsible for 52 percent of the total DALYs, with diabetes mellitus, anxiety and depression, and Alzheimer's disease and other dementias being the main sources of the total YLDs. Ischaemic heart disease, stroke and lung cancer were the major contributors to the premature mortality burden (YLL). CONCLUSION: This study provides an objective and systematic assessment of the fatal and nonfatal health conditions in Singapore to support priority setting in public health policies and research.

Demography and clinical course of ulcerative colitis in a multiracial Asian population: a nationwide study from Malaysia.

OBJECTIVE: To establish the clinical course of ulcerative colitis (UC) in the Malaysian population, comparing the three major ethnic groups: Malay, Chinese and Indian. METHODS: Patients who were diagnosed with UC from seven major medical referral centers in Malaysia were recruited. Their baseline characteristics, and the extent of the disease, its clinical course and complications were recorded. RESULTS: A total of 118 patients was included. The extent of disease was as follows: proctitis alone in 22 (18.6%), sigmoid colon in 23 (19.5%), descending colon in 16 (13.6%), transverse colon in 11 (9.3%), ascending colon and pancolitis 46 (39%). Most patients had chronic intermittent disease. Extra-intestinal complications were seen in 27 (22.9%) patients and fulminant colitis was seen in four (3.4%). None developed colorectal cancer. The overall cumulative colectomy rates at 1, 5 and 10 years were 3.4% (CI: 0.9-8.5), 5.9% (CI: 1.9-13.2) and 15.6% (CI: 6.5-29.4), respectively. There was a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease among Indian patients. However, no significant differences were seen in the age of onset, the severity of disease (fulminant colitis, refractory disease) and the colectomy rate. CONCLUSION: As in developed countries, most of our patients have a remitting and relapsing pattern of disease but the clinical course appears to be milder, with lower rates of colectomies. There are differences in clinical presentation among the three major ethnic groups, with Indians having a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease.

Diagnostic accuracy of CT angiography in acute gastrointestinal bleeding.

The aim of the study was to carry out a systematic review determining the accuracy of CT angiography in the diagnosis of acute gastrointestinal bleeding. A search of published work in Medline and manual searching of reference lists of articles was conducted. Studies were included if they compared CT angiography to a reference standard of upper gastrointestinal endoscopy, colonoscopy, angiography or surgery in the diagnosis of acute gastrointestinal bleeding. Eight published studies evaluating 129 patients were included. Data were used to form 2 x 2 tables. Computed tomography angiography showed pooled sensitivity of 86% (95% confidence interval 78-92%) and specificity of 95% (95% confidence interval 76-100%), without showing significant heterogeneity (chi(2) = 3.5, P = 0.6) and (chi(2) = 5.4, P = 0.6), respectively. Summary receiver operating characteristic analysis showed an area under the curve of 0.93. Computed tomography angiography is accurate in the diagnosis of acute gastrointestinal bleeding and can show the precise location and aetiology of bleeding, thereby directing further management. Strong recommendations for use of CT cannot be made from this review because of the methodological limitations and further large prospective studies are needed to define the role of CT in acute gastrointestinal bleeding.

Building partnerships to address the HIV epidemic.

INTRODUCTION: Batam is one of the islands comprising the Riau Province in Indonesia, and is closest to Singapore. It is a popular destination of many Singaporeans. Surveillance reports among commercial sex workers conducted in Batam showed the prevalence rate of human immunodeficiency virus (HIV) is 16.2 percent. At the end of 2006, the total number of HIV-infected Singaporeans was 3,060, the majority being infected via heterosexual transmission. The aim of the Indonesian government is to rapidly scale up HIV treatment to those needing it. One of the factors critical to the rapid scale-up is healthcare worker training. METHODS: An intersectoral collaboration addressing the issue of HIV care and treatment with a hospital in Batam was created. The first activity of the collaboration was a two-day HIV training course conducted in February 2007. The aim of the course was to provide a basic understanding of HIV, as well as knowledge on common opportunistic infections that may present to a general hospital or clinical setting. RESULTS: 34 doctors from 23 institutions in Batam and three doctors from two hospitals in the Riau Islands attended the two-day HIV training course. The participants found the training very useful and highly relevant. CONCLUSION: This first HIV training provided a foundation to build on further HIV education. It is our belief that through the HIV training programme, there will be more awareness of HIV among the various medical institutions in Batam. As the HIV epidemic knows no borders, working with neighbouring countries is one strategy that deserves attention.