Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Update on the Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings-review of evidence on the definition of high blood pressure and goal of therapy.

The Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings is updated regularly to ensure it reflects the latest medical development and best practice. In 2017, guidelines from the United States included a major change, adopting the lower blood pressure values of 130/80 mm Hg in defining hypertension, in contrast to the prevailing international consensus of 140/90 mm Hg. After thorough review of the literature and international guidelines, the Advisory Group on Hong Kong Reference Framework for Care of Diabetes and Hypertension in Primary Care Settings (Advisory Group) recommends that the definition of hypertension adopted in the Reference Framework should remain unchanged as a blood pressure of ≥140/90 mm Hg, as there is currently inadequate evidence and lack of general consensus to support such change in Hong Kong. The Advisory Group agrees on individualised treatment goals, and recommends that the initial blood pressure goal for individuals with uncomplicated hypertension should be <140/90 mm Hg; for those who can tolerate it, the goal should be ≤130/80 mm Hg. A lower blood pressure is advisable for young or overweight/obese patients, smokers, and patients with other cardiovascular risk factors.

Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma.

BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. METHODS: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.

Clonorchis sinensis infection is positively associated with atopy in endemic area.

BACKGROUND: Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported. OBJECTIVE: We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis. METHODS: A total of 1116 subjects (males 419, females 697; age range, 30-86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis-specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR). RESULTS: Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199-2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050-2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448-4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis. CONCLUSION AND CLINICAL RELEVANCE: Clonorchiasis was positively associated with atopy in adults in endemic area.

Population attributable fraction of infection-related cancers in Korea.

BACKGROUND: A number of infectious agents have been classified as human carcinogens. The purpose of the current study was to provide an evidence-based assessment of the burden of infection-related cancers in the Korean population. MATERIALS AND METHODS: The population attributable fraction was calculated using infection prevalence data from 1990 or earlier, relative risk estimates from meta-analyses using mainly Korean studies and national data on cancer incidence and mortality for the year 2007. RESULTS: The fractions of all cancers attributable to infection were 25.1% and 16.8% for cancer incidence in men and women, and 25.8% and 22.7% of cancer mortality in men and women, respectively. Among infection-related cancers, Helicobacter pylori was responsible for 56.5% of cases and 45.1% of deaths, followed by hepatitis B virus (HBV) (23.9% of cases and 37.5% of deaths) and human papillomavirus (HPV) (11.3% of cases and 6% of deaths) and then by hepatitis C virus (HCV) (6% of cases and 9% of deaths). Over 97% of infection-related cancers were attributable to infection with H. pylori, HBV, HCV and HPV. CONCLUSION: Up to one-quarter of cancer cases and deaths would be preventable through appropriate control of infectious agents in Korea.

Global health: challenges and opportunities for Singapore.

Over the past decade, global health has evolved from a buzzword to a discipline, attracting interest from governments, academic institutions and funding organisations. Global health centres, institutes and initiatives in Western countries have increased in both size and number, aided primarily by institutional backing and supportive funding mechanisms. As the rise to prominence of global health on the public health agenda also coincides with shifts in global balances of power, Asia, as well as Singapore, has an expanded role to play in supporting global health teaching and research, both in the region and throughout the world. Foundations, universities, government agencies, statutory boards and the private sector all have an important role to play in moving the global health agenda forward in Singapore. Rigorous global health training and increased funding for global health research are now timely and essential in order for global health, as a discipline, to develop within Singapore and have an impact within the region.

Combined effect of socioeconomic status, viral hepatitis, and lifestyles on hepatocelluar carcinoma risk in Korea.

BACKGROUND: The independent and combined effects of socioeconomic status (SES), viral hepatitis, and other lifestyle factors on hepatocellular carcinoma (HCC) risk have not been investigated among Koreans. METHODS: From the National Cancer Center Hospital, 207 HCC cases and 828 age- and gender-matched controls aged 30 years or older were recruited. Socio-demographic and behavioural risk factors were ascertained through personal interview, and infection with hepatitis B and C viruses was determined by their serologic markers. Multivariate logistic regression and synergy index methods were applied for statistical analysis. RESULTS: HB surface antigen (HbsAg) and anti-HCV-positive rates were 149.3 and 185.1 times higher in cases than controls, respectively. Lifetime alcohol consumption (odds ratio: 2.96, 95% CI: 1.29-6.79), cigarette smoking (OR: 3.53, 95% CI: 1.31-9.52), and family income (OR: 17.07, 95% CI: 4.27-68.25) were independently associated with the risk of HCC in subjects with or without viral hepatitis. Synergistic interaction on HCC risk was observed between low income and HBsAg positivity (SI: 3.12, 95% CI: 1.51-6.47) and between low income and heavy alcohol intake (SI: 2.93, 95% CI: 1.24-6.89). CONCLUSION: The inverse association with SES suggests SES as an independent and synergistic predictor of HCC. Heavy alcohol intake also showed a combined effect with low SES on HCC risk.

IAN5 polymorphisms are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is frequently associated with lymphopenia. Biobreeding (BB) rat is a typical animal model which develops autoimmune diseases with lymphopenia which results from a frame-shift mutation in the immune-associated nucleotide (IAN) 5 gene. IAN5 is involved in the regulation of T-cell activation and survival. To examine the association of IAN5 gene with SLE, we scrutinised the single nucleotide polymorphisms (SNPs) in the IAN5 gene. We conducted a case-control study where 132 SLE patients, 505 rheumatoid arthritis (RA) patients, and 546 controls were genotyped for four SNPs in the IAN5 gene. Two SNPs (+2071C > T and +2677G > A) were associated with susceptibility to SLE (P = 0.040 and 0.045, respectively), and -4432G > A SNP was associated with the development of leukopenia (P = 0.028) and the requirement of steroid pulse therapy (P = 0.040) in SLE patients. Haplotype analyses showed that Ht1(CTCG) was associated with susceptibility to SLE (P = 0.036), and Ht4(ACCG), Ht5(ACTA) and Ht6(GCCG) were associated with the development of nephritis (P = 0.017, 0.019, 0.022, respectively). In conclusion, the IAN5 polymorphisms were associated with susceptibility to SLE and the development of clinical disease manifestations in a strictly Korean population.

Detection of Clonorchis sinensis in stool samples using real-time PCR.

Human clonorchiasis, caused by infection with the trematode Clonorchis sinensis, is a common health problem in East Asia. In an attempt to develop a new, sensitive method for the diagnosis of the disease, the use of a real-time PCR (targeting the internal-transcribed-spacer-2 sequence of the parasite) to detect C. sinensis-specific DNA in faecal samples has recently been evaluated. The PCR-based assay, which included an internal control to detect any inhibition of the amplification by faecal constituents in the sample, was performed on stool samples and on DNA controls representing a wide range of intestinal microorganisms. The assay appeared very specific, only showing positivity with C. sinensis and Opisthorchis felineus. The sensitivity of the assay was explored by testing 170 preselected samples of human faeces, from an endemic area of South Korea, which had known (microscopically-determined) densities of C. sinensis eggs. The sensitivity of the assay was 100% for the 74 samples that each had > 100 eggs/g and 91.4% for the other 70 samples found egg-positive by microcopy (i.e. those that had

The intravertebral cleft in benign vertebral compression fracture: the diagnostic performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI.

We compared the diagnostic performance of non-enhanced MRI and fat-suppressed contrast-enhanced MRI (CEMRI) in diagnosing intravertebral clefts in benign vertebral compression fractures (VCFs). We retrospectively reviewed 99 consecutive patients who had undergone percutaneous vertebroplasty for VCFs. A cleft was defined as a signal void or hyperintense area on non-enhanced MRI (T(1) and T(2) weighted imaging) or as a hypointense area within a diffusely enhanced vertebra on CEMRI. A cleft was confirmed as a solid opacification on post-procedural radiographs. The interobserver reliability and MRI diagnostic performance were evaluated. The interobserver reliability of non-enhanced MRI was substantial (k _ 0.698) and the interobserver reliability of CEMRI was almost perfect (k _ 0.836). Post-procedural radiographs showed solid cleft opacification in 32 out of the 99 cases. The sensitivity and specificity of non-enhanced MRI were 0.72 and 0.82 (observer 1) and 0.63 and 0.87 (observer 2), respectively. The sensitivity and specificity of CEMRI were 0.94 and 0.63 (observer 1) and 0.85 and 0.60 (observer 2), respectively. The sensitivity of CEMRI was significantly higher than that of non-enhanced MRI, and the specificity of non-enhanced MRI was higher than that of CEMRI. CEMRI was highly reliable and sensitive, and non-enhanced MRI was specific for intravertebral clefts. Therefore, spine MRIs, including CEMRI, could provide useful information about intravertebral clefts before percutaneous vertebroplasty.

Does child gender determine household decision for health care in rural Thatta, Pakistan?

BACKGROUND: In South Asia, gender disparity in child mortality is highest in Pakistan. We examined the influence of child gender on household decision regarding health care. METHODS: Prevalence ratios were calculated for 3740 children aged 1-59 months from 92 randomly selected villages of rural Pakistan using a cluster-adjusted log-binomial model. Level 1 variables included child and household characteristics and level 2 included village characteristics. RESULTS: There were 25 more girl deaths than boys per 1000 live births (95% CI: 13.9, 48.6) among post-neonates and 38 more among children aged 12-59 months (95% CI: 10.5, 65.5). However, in adjusted analysis, gender was not a significant predictor of illness reporting, visit to health facilities, choice of provider, hospitalization and health expenditure. Significant predictors of health care were child's age, illness characteristics, number of children in the family, household socio-economic status and absence of girls' school in the village. CONCLUSIONS: Differential care seeking for boys and girls is not seen in Thatta despite clear differences in mortality ratios. This calls for more creative research to identify pathways for gender differential in child mortality. Factors identified as influencing child health care and amenable to modification include poverty alleviation and girls' education.

Abnormal thalamic volume in treatment-naïve boys with Tourette syndrome.

OBJECTIVE: Thalamic abnormality has been implicated in the pathophysiology of Tourette's syndrome (TS). We examined the presence of aberrant thalamic volume from the treatment-naïve boys with TS using magnetic resonance imaging (MRI). METHOD: Volumetric MRI was performed on 18 treatment-naïve boys with TS, aged 7-14 years, and 16 healthy comparison subjects. The anatomical boundaries were then manually parcellated to measure the thalamic volume. RESULTS: Tourette's syndrome subjects had a significantly larger left thalamus in comparison with those of healthy subjects. On the contrary, no group difference was observed from the right thalamic volume. TS subjects also showed a significant reduction in rightward asymmetry in thalamic volume compared with the healthy subjects. CONCLUSION: Our findings provide new evidence of abnormal thalamic volume in pediatric TS.

Transforming Singapore health care: public-private partnership.

Prudent health care policies that encourage public-private participation in health care financing and provisioning have conferred on Singapore the advantage of flexible response as it faces the potentially conflicting challenges of becoming a regional medical hub attracting foreign patients and ensuring domestic access to affordable health care. Both the external and internal health care markets are two sides of the same coin, the competition to be decided on price and quality. For effective regulation, a tripartite model, involving not just the government and providers but empowered consumers, is needed. Government should distance itself from the provider role while providers should compete - and cooperate - to create higher-value health care systems than what others can offer. Health care policies should be better informed by health policy research.

Appropriate use of personal protective equipment among healthcare workers in public sector hospitals and primary healthcare polyclinics during the SARS outbreak in Singapore.

BACKGROUND: Singapore was affected by an outbreak of severe acute respiratory syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33 deaths. AIMS: To study usage of personal protective equipment (PPE) among three groups of healthcare workers (HCWs: doctors, nurses, and administrative staff), to determine if the appropriate PPE were used by the different groups and to examine the factors that may determine inappropriate use. METHODS: A self-administered questionnaire survey of 14,554 HCWs in nine healthcare settings, which included tertiary care hospitals, community hospitals, and polyclinics, was carried out in May-July 2003. Only doctors, nurses, and clerical staff were selected for subsequent analysis. RESULTS: A total of 10 236 valid questionnaires were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the administrative staff agreed that paper and/or surgical masks were "useful in protecting from contracting SARS". Among this group, 23.6% of doctors and 42.3% of nurses reported working with SARS patients. The view that a paper and/or surgical mask was adequate protection against SARS was held by 33.3% of doctors and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care units. Factors which predicted for agreement that paper and/or surgical masks were protective against SARS, included HCW's job title, reported contact with SARS patients, area of work, and Impact Events Scale scores. CONCLUSION: A variety of factors determine appropriate use of personal protective equipment by HCWs in the face of a major SARS outbreak.

Complementary and alternative medicine use in multiracial Singapore.

OBJECTIVE: To determine the prevalence of complementary and alternative medicine (CAM) use in Singapore, the factors influencing CAM use, and the attitudes, beliefs and perceptions of the general population towards CAM. DESIGN: An interviewer-administered questionnaire survey in a housing estate with demographic and socioeconomic characteristics closely matching that of Singapore. RESULTS: 76% (95% C.I. 73.9-77.9%) used CAM over a 12-month period. Females were 2.1 times (95% C.I. 1.3-3.4) more likely than males to use CAM. Chinese (84%) were the most frequent users, followed by Malays (69%) and Indians (69%), with adjusted odds ratios of 0.4 (95% C.I. 0.2-0.7) for Malays and 0.4 (95% C.I. 0.2-0.8) for Indians. Traditional Chinese Medicine (88%) was the most widely used form of CAM, followed by Traditional Malay (Jamu) Medicine (8%) and Traditional Indian (Ayuverdic) Medicine (3%). Similar to western studies, CAM was more likely to be used for maintenance of health than for treatment of illness. Different from western studies, CAM use was not independently associated with household income, marital status, age and education. Seventy-four percent did not discuss their use of CAM with their western-trained doctors. CONCLUSIONS: The high prevalence of CAM use in multi-racial Singapore suggests the same may be true in other Asian countries. Western-trained doctors need to understand CAM better and communicate more with their patients regarding CAM use. The lack of a scientific evidence base for most forms of CAM notwithstanding, its ubiquitous use worldwide is something that governments and the medical profession cannot afford to ignore.

Quest for quality care and patient safety: the case of Singapore.

Quality of care in Singapore has seen a paradigm shift from a traditional focus on structural approaches to a broader multidimensional concept which includes the monitoring of clinical indicators and medical errors. Strong political commitment and institutional capacities have been important factors for making the transition. What is still lacking, however, is a culture of rigorous programme evaluation, public involvement, and patient empowerment. Despite these imperfections, Singapore has made considerable strides and its experience may hold lessons for other small developing countries in the common quest for quality care and patient safety.

Cosmic rays: are air crew at risk?

This article reviews the current knowledge about cosmic rays and their possible effects on health of air crew, discusses research directions necessary for establishing and measuring the risks, and highlights the need for physicians and air crew to be informed, despite the inconclusiveness of the evidence. A literature review of computerised medical and scientific databases was carried out. Recent reports highlighting increased incidence of cancer among airline pilots and cabin crew have renewed concerns about possible exposure to harmful levels of cosmic radiation at altitude. Such low energy ionising radiation has been shown to cause double stranded DNA deletions and induce genomic instability in human chromosomes. In the field of microelectronics, cosmic rays have been shown to cause "hard" and "soft" errors in computer microchips, in a dose-response fashion with increasing altitude. Pregnant cabin crew members are of special concern. Although the epidemiological evidence is still inconclusive, we know enough to warrant a cautionary stance. The European Union (EU) leads the way in legislation.

A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.

Exposure of airline pilots and cabin crew to cosmic radiation during flight--what's the fuss?

The International Commission on Radiological Protection (ICRP) had in 1990 recommended that civilian aircrew be classified as being occupationally exposed to low-dose ionizing radiation, in view of their increased exposure to cosmic rays at altitude. In 2000, the European Union had gone ahead with legislation which requires all European airlines to monitor cosmic radiation levels during flight and to inform aircrew of the possible health risks. However, the evidence for a causal link between cosmic radiation exposure and health risks remains elusive despite recent findings of increased cancer incidence among airline pilots and cabin crew. The inconclusiveness of the evidence notwithstanding, there are compelling reasons for adopting a prudent and precautionary stance.