Retrospective study found that outpatient care for infants exposed to drugs during pregnancy was sustainable and safe.

AIM: We determined the safety, feasibility and sustainability of an outpatient model of care for infants exposed to intra-uterine drugs. METHODS: This was a retrospective chart review of 774 drug-exposed infants born between 1998 and 2016 at the Royal Hospital for Women, Sydney, Australia. RESULTS: Most (86%) of the mothers used multiple drugs, including opioids (58%). More than three-quarters (78%) of the infants were born full term at a mean gestation of 38 weeks and hospitalised for a median of seven days. This rose to 14 days if they were medicated for neonatal abstinence syndrome (NAS). Most of the NAS patients (83%) were discharged on medication, namely morphine, and the median duration of NAS treatment was 76 (interquartile range 35-120). Three medication errors occurred: two extra doses of phenobarbitone and one infant weaned off morphine faster than prescribed. No infants were rehospitalised for NAS. Four died from sudden infant death syndrome at 2.2-5.8 months after discharge and one drowned at 15 months. None were medicated at the time of death. CONCLUSION: Outpatient care for drug-exposed infants was sustainable and had low complication rates, even for those with NAS. The optimum duration of follow-up and impact on hospital costs should be examined.

Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization.

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.

Twin pregnancies complicated by gestational diabetes mellitus: a single centre cohort study.

AIMS: In women with a twin pregnancy, to determine the incidence of, risk factors for and outcomes of women with gestational diabetes mellitus, and assess how these have changed with a change in gestational diabetes screening. METHODS: Retrospective cohort study of women with a twin pregnancy attending an Australian tertiary hospital, 2002-2013. Information on gestational diabetes status, gestational diabetes risk factors and pregnancy outcomes was ascertained. Pregnancy outcomes included hypertensive disorders, twin birthweight centile and a composite adverse pregnancy outcome. Analysis was stratified pre/post screening protocol change (epoch 1: 2002-2009, epoch 2: 2010-2013) and by gestational diabetes status. RESULTS: Gestational diabetes was diagnosed in 86/982 (8.8%) women, increasing from 4.4% to 14.7% between epochs (P = 0.0001). The proportion of women with hypertensive disorders increased (11.7% vs. 13.4%, P = 0.009), but the proportion of infant's birthweight > 90th centile decreased (11.0% vs. 7.6%, P = 0.02) between epochs. Overall, 33.6% of women had ≥ 1 risk factors for gestational diabetes. Three-quarters (73.7%) of women overall had an adverse pregnancy outcome, with a slightly higher proportion in women with gestational diabetes compared with those with no gestational diabetes (79.7% vs. 73.1%, P = 0.06). The rate of the adverse pregnancy outcome did not change by epoch, after adjusting for maternal and pregnancy risk factors (adjusted odds ratio = 0.96, 95% confidence interval 0.73-1.26). CONCLUSIONS: Almost 1 in 10 women with a twin pregnancy were diagnosed with gestational diabetes, with the incidence of gestational diabetes increasing threefold with a new screening protocol. The pregnancy outcomes of women with a twin pregnancy did not change with increased detection and treatment for gestational diabetes.

High burden of RSV hospitalization in very young children: a data linkage study.

Linked administrative population data were used to estimate the burden of childhood respiratory syncytial virus (RSV) hospitalization in an Australian cohort aged <5 years. RSV-coded hospitalizations data were extracted for all children aged <5 years born in New South Wales (NSW), Australia between 2001 and 2010. Incidence was calculated as the total number of new episodes of RSV hospitalization divided by the child-years at risk. Mean cost per episode of RSV hospitalization was estimated using public hospital cost weights. The cohort comprised of 870 314 children. The population-based incidence/1000 child-years of RSV hospitalization for children aged <5 years was 4·9 with a rate of 25·6 in children aged <3 months. The incidence of RSV hospitalization (per 1000 child-years) was 11·0 for Indigenous children, 81·5 for children with bronchopulmonary dysplasia (BPD), 10·2 for preterm children with gestational age (GA) 32-36 weeks, 27·0 for children with GA 28-31 weeks, 39·0 for children with GA <28 weeks and 6·7 for term children with low birthweight. RSV hospitalization was associated with an average annual cost of more than AUD 9 million in NSW. RSV was associated with a substantial burden of childhood hospitalization specifically in children aged <3 months and in Indigenous children and children born preterm or with BPD.

CT-guided percutaneous core-needle biopsy of pancreatic masses: comparison of the standard mesenteric/retroperitoneal versus the trans-organ approaches.

AIM: To compare the safety and efficacy of percutaneous computed tomography (CT)-guided core-needle biopsy (CNB) of pancreatic masses traversing the gastrointestinal tract or solid viscera versus trans-mesenteric and retroperitoneal approaches. MATERIALS AND METHODS: CT-guided CNB of pancreatic lesions performed between May 2004 and December 2014 were retrospectively analysed at a single centre. Biopsies were performed using 18- or 20-G needles with a coaxial system. CT images, histopathology reports, medical records, and procedural details for all patients were reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. According to the routes, biopsies were divided into trans-mesenteric, retroperitoneal and trans-organ approaches for comparison. RESULTS: A total of 85 patients, who had undergone 89 CNBs for pancreatic masses were reviewed. The overall sensitivity, specificity, and accuracy of CNB for detecting malignancy via various routes were 88.8%, 100%, and 89.9%, respectively, with a complication rate of 20.2%. Trans-organ biopsies of pancreatic masses (n=22) were performed safely via a direct pathway traversing the stomach (n=14), colon (n=3), small bowel (n=2), liver (n=2), and spleen (n=1). The sensitivity, specificity, and accuracy were 90.5%, 100%, and 90.9%, respectively. In the trans-organ biopsy group, three biopsies (13.6%) resulted in minor haematomas, but no major complications occurred. There were no statistically significant differences in the diagnostic efficacy or complication rate among the different biopsy routes. CONCLUSION: Percutaneous CT-guided CNB using a trans-organ approach is a feasible technique for diagnosing pancreatic malignancy; however, as this series was small, more data is required.

Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air.

AIM: The starting fraction of inspired oxygen for preterm resuscitation is a matter of debate, and the use of room air in full-term asphyxiated infants reduces oxidative stress. This study compared oxidative stress in preterm infants randomised for resuscitation with either 100% oxygen or room air titrated to internationally recommended levels of preductal oxygen saturations. METHODS: Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room air (n = 59). Oxidative stress markers, including advanced oxidative protein products (AOPP) and isoprostanes (IsoP), were measured with high-performance liquid chromatography and mass spectrometry. RESULTS: Significantly higher levels of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations were significantly higher in the 100% oxygen group. CONCLUSION: Initial resuscitation with room air versus 100% oxygen was associated with lower protein oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels between two and 12 hours of life. Correlations with clinical outcomes will be vital to optimise the use of oxygen in preterm resuscitation.

Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.

Since the publication of the Hong Kong Epilepsy Guideline in 2009, there has been significant progress in antiepileptic drug development. New AEDs have emerged, and data about their uses have been published. Women require special attention in epilepsy care. Drug teratogenicity, pregnancy, breastfeeding, contraception, reproduction technology, menopause, and catamenial epilepsy are major topics. Antiepileptic drugs should be chosen individually for patients who are pregnant or may become pregnant with consideration of their teratogenicity and seizure control properties. Folate is commonly prescribed for women of childbearing age who are taking antiepileptic drugs. Spontaneous vaginal delivery and breastfeeding are not contra-indicated in most cases but need to be considered individually based on the patient's medical condition and wishes. Serum drug level monitoring of certain antiepileptic drugs during pregnancy and puerperium can guide dosage adjustment. For catamenial epilepsy, intermittent benzodiazepines such as clobazam during the susceptible phase of the menstrual cycle could be a treatment option.

Trans-organ versus trans-mesenteric computed tomography-guided percutaneous fine-needle aspiration biopsy of pancreatic masses: feasibility and safety.

AIM: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous fine-needle aspiration biopsy (FNAB) of pancreatic masses that traverses the gastrointestinal tract or solid viscera. MATERIALS AND METHODS: From January 2002 to December 2012, 144 patients underwent 165 CT-guided biopsies of pancreatic masses. Biopsies were performed using a 21 or 22 G needle. Cytology reports, medical records, and procedure details for all patients were retrospectively reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. RESULTS: Trans-organ biopsies of pancreatic masses were safely performed via a direct pathway traversing the stomach (n = 45), colon (n = 14), jejunum (n = 4), or liver (n = 5). There were five self-limiting mesenteric haematomas along the biopsy route on immediate post-procedure CT and all patients remained asymptomatic. All haematomas occurred after a trans-mesenteric approach rather than passage through abdominal organs. Three patients had acute pancreatitis. There was no significant difference in complications and diagnostic yields between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value of final FNAB cytology for malignancy were 98.3%, 100%, 100% and 71.4%, respectively. The overall accuracy was 98.4%. CONCLUSION: Percutaneous FNAB using the trans-organ approach is a safe and effective technique to diagnose pancreatic malignancy.

Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal stent used for inoperable cholangiocarcinoma.

A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an uncovered metal stent inserted for palliative drainage. About 1.5 years later, tumour ingrowth into the metal stent caused cholangitis. Intraductal radiofrequency ablation was applied to create local coagulative tumour necrosis and the necrotic tissue was removed via a balloon catheter. A plastic stent was inserted to empirically treat any ensuing potential bile duct injury. The patient was discharged without complication with good palliative drainage. Intraductal radiofrequency ablation is a new technique for the treatment of metal stent occlusion due to tumour ingrowths. This is the first case report of this relatively safe and feasible new technique for the treatment of tumour ingrowth into a metal stent used as palliation for malignant biliary obstruction.

Effect of wearing an N95 respirator on the internal nasal valve and the association with external nasal anatomy - a cohort study.

OBJECTIVES: To determine whether: the N95 respirator affects nasal valve patency; placement on the bony vault improves patency; and external nasal anatomy affects the outcome. METHODS: A prospective study with 50 participants was conducted. Nasal patency was measured by the minimal cross-sectional area via acoustic rhinometry, and using the Nasal Obstruction Symptom Evaluation survey, before and after wearing the N95 respirator and after adjustment. RESULTS: The minimal cross-sectional area was narrowed by 27 per cent when wearing the N95 respirator (p < 0.001), and improved by 9.2 per cent after adjustment (p = 0.003). The total Nasal Obstruction Symptom Evaluation score increased from 10.2 to 25.4 after donning the N95 respirator (p < 0.001), and decreased from 25.4 to 15.6 after adjustment (p < 0.001). There was no correlation with external nasal anatomy parameters. CONCLUSION: Wearing the N95 respirator causes narrowing of the nasal valve, and adjustment onto the bony vault improves symptoms. The findings were not affected by external nasal anatomy.

Alcohol Consumption and Depression Among University Students and Their Perception of Alcohol Use.

OBJECTIVES: To investigate the association between alcohol use and depression among university students in Hong Kong, their stress-coping methods, and their knowledge and perception of the effects of alcohol on health. METHODS: 345 full-time undergraduate students from The University of Hong Kong were invited to complete a questionnaire to assess their alcohol consumption (Alcohol Use Disorders Identification Test, CAGE questionnaire), depressive symptoms (Patient Health Questionnaire-9), and stress-coping methods (Coping Orientation to Problems Experienced Inventory), as well as knowledge and perception of alcohol consumption on health. Multiple linear regression was used to determine significant variables associated with depressive symptoms. Multinominal logistic regression was used to determine the effect of such variables on depressive symptom caseness and AUDIT drinking risk groups. RESULTS: 43.2% of respondents were moderate- to high-risk drinkers, but only 23.2% were self-reported as moderate- to high-level drinkers. 57.9% of respondents had mild to severe depressive symptoms. Probable depression was more likely to occur in female students, those with higher general stress, those who do not use social support for stress-coping, and those who smoke. High-risk drinkers were more likely to occur in older students, smokers, those with higher household income, and those with higher general stress levels. Students with higher levels of depressive symptoms and higher risk of alcohol consumption were more likely to use avoidance for stress-coping. 89.5% of students considered alcohol consumption moderately to very harmful to health, but students demonstrated only moderate knowledge levels of alcohol consumption on health. CONCLUSION: Alcohol consumption and depressive symptoms are prevalent among university students in Hong Kong. The use of avoidance for stress-coping is common in those with higher levels of depressive symptoms and higher-risk drinkers. Students tend to avoid seeking help for depressive symptoms and potentially take up drinking as a coping strategy. Context-specific approaches should be used when providing counselling services for student wellbeing in university settings. Further education of university students on knowledge and perception of alcohol consumption on health should be provided.

The chemical composition and toxicological effects of fine particulate matter (PM2.5) emitted from different cooking styles.

The mass, chemical composition and toxicological properties of fine particulates (PM2.5) emitted from cooking activities in three Hong Kong based restaurants and two simulated cooking experiments were characterized. Extracts from the PM2.5 samples elicited significant biological activities [cell viability, generation of reactive oxygen species (ROS), DNA damage and inflammation effect (TNF-α)] in a dose-dependent manner. The composition of PAHs, oxygenated PAHs (OPAHs) and azaarenes (AZAs) mixtures differed between samples. The concentration ranges of the Σ30PAHs, Σ17OPAHs and Σ4AZAs and Σ7Carbonyls in the samples were 9627-23,452 pg m-3, 503-3700 pg m-3, 33-263 pg m-3 and 158 - 5328 ng m-3, respectively. Cell viability caused by extracts from the samples was positively correlated to the concentration of benzo[a]anthracene, indeno[1,2,3-cd]pyrene and 1,4-naphthoquinone in the PM2.5 extracts. Cellular ROS production (upon exposure to extracts) was positively correlated with the concentrations of PM2.5, decaldehyde, acridine, Σ17OPAHs and 7 individual OPAHs. TNF-α showed significant positive correlations with the concentrations of most chemical species (elemental carbon, 16 individual PAHs including benzo[a]pyrene, Σ30PAHs, SO42-, Ca2+, Ca, Na, K, Ti, Cr, Mn, Fe, Cu and Zn). The concentrations of Al, Ti, Mn, Σ30PAHs and 8 individual PAHs including benzo[a]pyrene in the samples were positively correlated with DNA damage caused by extracts from the samples. This study demonstrates that inhalation of PM2.5 emitted from cooking could result in adverse human health effects.

CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity.

Recent data indicate that the cell surface glycoprotein CD5 functions as a negative regulator of T cell receptor (TCR)-mediated signaling. In this study, we examined the regulation of CD5 surface expression during normal thymocyte ontogeny and in mice with developmental and/or signal transduction defects. The results demonstrate that low level expression of CD5 on CD4(-)CD8(-) (double negative, DN) thymocytes is independent of TCR gene rearrangement; however, induction of CD5 surface expression on DN thymocytes requires engagement of the pre-TCR and is dependent upon the activity of p56(lck). At the CD4(+)CD8(+) (double positive, DP) stage, intermediate CD5 levels are maintained by low affinity TCR-major histocompatibility complex (MHC) interactions, and CD5 surface expression is proportional to both the surface level and signaling capacity of the TCR. High-level expression of CD5 on DP and CD4(+) or CD8(+) (single positive, SP) thymocytes is induced by engagement of the alpha/beta-TCR by (positively or negatively) selecting ligands. Significantly, CD5 surface expression on mature SP thymocytes and T cells was found to directly parallel the avidity or signaling intensity of the positively selecting TCR-MHC-ligand interaction. Taken together, these observations suggest that the developmental regulation of CD5 in response to TCR signaling and TCR avidity represents a mechanism for fine tuning of the TCR signaling response.

T cell development in mice lacking all T cell receptor zeta family members (Zeta, eta, and FcepsilonRIgamma).

The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.

Safe use of local anaesthetics: prevention and management of systemic toxicity.

Local anaesthetic administration is a common clinical practice not only in the operating theatres, but also in other clinical settings. Relevant monitoring and resuscitation facilities in certain clinical settings outside the operation rooms may not be optimal. Despite the low incidence of severe complications associated with administration of local anaesthetics, their safe use is very important since systemic toxicity can be fatal. This article reviews the pharmacology of local anaesthetics, clinical features of systemic toxicity resulting from their local use, and necessary preventive measures and management. The role of lipid emulsion therapy is also discussed.

CHECK: A randomized trial evaluating the efficacy and cost-effectiveness of home visitation in pediatric weight loss treatment.

BACKGROUND: Socioeconomically-disadvantaged households have a high prevalence of pediatric overweight/obesity, and also face barriers to accessing weight loss treatment in healthcare settings. Delivering family-based pediatric weight loss treatment in the home setting may enhance its efficacy by facilitating treatment attendance, enabling more tailored treatment recommendations informed by observations of the home environment, and increasing accountability. This paper describes the design of the Creating Health Environments for Chicago Kids (CHECK) Trial, which evaluates the efficacy, cost-effectiveness, and mechanisms of home visitation in family-based pediatric weight loss treatment for children in low-income households. DESIGN: CHECK is a two-arm, parallel group, randomized controlled trial that is enrolling N = 266 children, ages 6-12 y, who have overweight/obesity (BMI percentile ≥85) and live in a low-income household. Participants are randomized in a 1:1 ratio to either standard of care family-based weight loss treatment delivered in the home, or the identical intervention delivered in an academic medical center. The primary outcome is change in child BMI z-score from baseline to 12 months. Program delivery costs are rigorously documented to enable cost-effectiveness analyses from the societal and payer perspectives. Objectively-documented changes to the home environment and aspects of intervention delivery (e.g., hours of in-person contact received, quantity of behavioral goals set per session) will be tested as hypothesized treatment mechanisms. IMPLICATIONS: Findings will inform the design of future interventions, and treatment dissemination decisions by public health agencies and third-party payers. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03195790.

A model-based estimate of the mean incubation period for AIDS in homosexual men.

Because of the difficulty in identifying the date of exposure to type 1 of the human immunodeficiency virus (HIV-1) infection in persons other than transfusion recipients, studies of the incubation periods for acquired immunodeficiency syndrome (AIDS) have been limited. When data from a cohort of 84 homosexual and bisexual men that provided the information to determine the years of conversion of sera infected with HIV-1 were analyzed, a model for the proportion likely to develop AIDS and the incubation period for AIDS in homosexual men could be derived. The maximum likelihood estimate for the proportion of infected homosexual men developing AIDS is 0.99 (90% confidence interval ranging from 0.38 to 1). Furthermore, the maximum likelihood estimate for the mean incubation period for AIDS in homosexual men is 7.8 years (90% confidence interval ranging from 4.2 years to 15.0 years), which is close to the estimate of 8.2 years for adults developing transfusion-associated AIDS.

The effects of particle-induced oxidative damage from exposure to airborne fine particulate matter components in the vicinity of landfill sites on Hong Kong.

The physical, chemical and bioreactivity characteristics of fine particulate matter (PM2.5) collected near (<1 km) two landfill sites and downwind urban sites were investigated. The PM2.5 concentrations were significantly higher in winter than summer. Diurnal variations of PM2.5 were recorded at both landfill sites. Soot aggregate particles were identified near the landfill sites, which indicated that combustion pollution due to landfill activities was a significant source. High correlation coefficients (r) implied several inorganic elements and water-soluble inorganic ions (vanadium (V), copper (Cu), chloride (Cl-), nitrate (NO3-), sodium (Na) and potassium (K)) were positively associated with wind flow from the landfill sites. Nevertheless, no significant correlations were also identified between these components against DNA damage. Significant associations were observed between DNA damage and some heavy metals such as cadmium (Cd) and lead (Pb), and total Polycyclic Aromatic Hydrocarbons (PAHs) during the summer. The insignificant associations of DNA damage under increased wind frequency from landfills suggested that the PM2.5 loading from sources such as regional sources was possibly an important contributing factor for DNA damage. This outcome warrants the further development of effective and source-specific landfill management regulations for particulate matter production control to the city.