We know DAAs work, so now what? Simplifying models of care to enhance the hepatitis C cascade.

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalized populations, particularly people who inject drugs (PWID), have low testing, linkage to care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale-up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: (i) review the evidence on MoCs for HCV; and (ii) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring.

Source Contributions to Wintertime Elemental and Organic Carbon in the Western Arctic Based on Radiocarbon and Tracer Apportionment.

To quantify the contributions of fossil and biomass sources to the wintertime Arctic aerosol burden source apportionment is reported for elemental (EC) and organic carbon (OC) fractions of six PM10 samples collected during a wintertime (2012-2013) campaign in Barrow, AK. Radiocarbon apportionment of EC indicates that fossil sources contribute an average of 68 ± 9% (0.01-0.07 µg m(-3)) in midwinter decreasing to 49 ± 6% (0.02 µg m(-3)) in late winter. The mean contribution of fossil sources to OC for the campaign was stable at 38 ± 8% (0.04-0.32 µg m(-3)). Samples were also analyzed for organic tracers, including levoglucosan, for use in a chemical mass balance (CMB) source apportionment model. The CMB model was able to apportion 24-53% and 99% of the OC and EC burdens, respectively, during the campaign, with fossil OC contributions ranging from 25 to 74% (0.02-0.09 µg m(-3)) and fossil EC contributions ranging from 73 to 94% (0.03-0.07 µg m(-3)). Back trajectories identified two major wintertime source regions to Barrow: the Russian and North American Arctic. Atmospheric lifetimes of levoglucosan, ranging from 50 to 320 h, revealed variability in wintertime atmospheric processing of this biomass burning tracer. This study allows for unambiguous apportionment of EC to fossil fuel and biomass combustion sources and intercomparison with CMB modeling.

Selective pressurized liquid extraction technique for halogenated organic pollutants in marine mammal blubber: a lipid-rich matrix.

Analytical methods for unique and rare samples, such as marine mammal tissue, strive to reduce opportunities for analyte loss and contamination. Historically, analytical methodologies for marine mammal tissues required an extraction followed by multiple cleanup and concentration steps. These steps increase the opportunity for analyte loss and sample contamination. Selective pressurized liquid extractions (SPLE; an analytical technique that combines PLE with in-cell adsorbent cleanup) have the potential to reduce and/or eliminate the number of steps. A SPLE method was developed for the simultaneous extraction of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) from bowhead whale blubber. This SPLE utilized acidic silica with a fat-to-fat retainer ratio of 0.02 as well as eliminated post-extraction cleanup steps, such as size-exclusion chromatography step. In addition, neutral silica was placed beneath the acidic silica as an acid buffer, thereby preventing acid from contaminating the extraction system. Analysis was performed using gas chromatography/mass spectrometry in electron capture negative ionization mode. PBDE, PCB and OCP triplicate recoveries averaged 84±1%, 83±3%, and 76±11%, respectively. Overall, measurements of NIST Whale Blubber SRM 1945 were within±30% of certified values. PBDEs were measured for the first time in bowhead whale blubber; average concentrations ranged from 0.2 to 1.4 ng g(-1) wet weight (ww). Average OCPs and PCBs concentrations ranged from 0.4 to 37 ng g(-1)ww and 0.1 to 3.0 ng g(-1)ww, respectively, which were within one order of magnitude lower than those previously reported in bowhead whale blubber.

Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine.

BACKGROUND AND AIM: Data from renal transplant and rheumatoid arthritis patients suggest that there is an increased risk of malignancy after treatment with azathioprine. Whether this is true for patients with inflammatory bowel disease remains uncertain. METHOD: A retrospective review of clinical notes was performed. RESULTS: Azathioprine was given to 626 of 2204 patients (855 with Crohn's disease and 1349 with ulcerative colitis). The mean total duration of azathioprine use was 27 months. The mean follow-up from diagnosis was 13.7 years and the mean follow-up from the start of azathioprine treatment was 6.9 years. Thirty-one cancers were observed in 30 patients treated with azathioprine (4.5%) and 77 cancers were observed in 70 patients not treated with azathioprine (4.5%; P=N.S.). Logistic regression analysis (including in the model the age, sex, diagnosis and extent of disease) showed that treatment with azathioprine did not significantly affect the risk of the development of cancer. Eight patients had lymphoma; three had been given azathioprine (P=N.S.). For patients with ulcerative colitis, the number of colorectal cancers (including high-grade dysplasia) in patients given azathioprine was eight of 355 (2.2%), compared with 28 of 994 (2.8%) for patients not given azathioprine (P=N.S.). The cumulative risk of colorectal cancer or dysplasia/dysplasia-associated lesion or mass (adjusted to exclude post-colectomy patients) after 10, 20, 30 and 40 years of ulcerative colitis was 0.4%, 1.3%, 9%and 15.5%, respectively. CONCLUSION: No increased risk of cancer diagnosis following azathioprine treatment was observed.

Adolescents' perceptions of a health survey using multimedia computer-assisted self-administered interview.

OBJECTIVE: To ascertain young people's perceptions of an adolescent health survey when administered by multimedia computer assisted self-administered Interview (M-CASI) through analysis of (1) questionnaire item responses and (2) focus group interviews. SETTING: Auckland, New Zealand, 1999. STUDY TYPE: Pilot testing of a 488-item branching questionnaire delivered using a youth-oriented and user-friendly M-CASI interface in a variety of settings using both desktop and laptop computers. Post pilot focus groups of participants identifying their perceptions and experiences of the survey. SAMPLE: 110 school students aged 12 to 18 years. RESULTS: The mean number of questions answered by participants was 316 with the median time to completion being 48 minutes. On average 65% of the total number of questions were seen and of these 1.5% were deliberately not answered. A high level of acceptability and enjoyment of M-CASI was found in the analysis of focus group responses and agreed with the item responses relating to M-CASI within the questionnaire itself. Participants identified privacy and confidentiality as being particularly important for the honesty of their responses. The passive matrix screens of the computers were popular as they could only be viewed from in front. CONCLUSIONS: M-CASI is an acceptable instrument for the administration of a youth health survey. Laptop computers with passive matrix screens are able to enhance perceptions of privacy and confidentiality, which may improve honesty of responses. IMPLICATIONS: M-CASI is now feasible and offers advantages in health surveying.

The changing presentation of children with newly diagnosed type 1 diabetes mellitus.

Although it is known that the incidence of type 1 diabetes mellitus (DM) in childhood is progressively increasing, it is less clear whether the presentation of newly diagnosed DM is changing. The aim of this study was to establish whether any biochemical or clinical presentation parameters have altered over time. A retrospective study was performed comparing newly diagnosed children with DM in two 24 month time intervals, 8 yrs apart (1988-89 and 1995-96). Fifty-seven children were diagnosed with type 1 DM in 1988-89 and 70 children in 1995-96. At presentation, children born in the later cohort had a higher pH (p < 0.001) and lower serum glucose (p < 0.05). Although the frequency of diabetic ketoacidosis (DKA) was higher in the 1988/89 cohort (63% vs. 42% in 1995/96) the absolute number of children with DKA in each time interval was similar (33 subjects in 1988-89 vs. 30 subjects in 1995/96). Islet cell antibody (ICA) levels were very different between the two cohorts; higher antibody levels were found in the 1988/89 group (p < 0.01). DKA was also associated with higher ICA titres (p < 0.05). Hospital admission stay decreased from 6.5 DS to 3.4 DS over the 8-year period (p < 0.0001). At our institution, the presentation of children with type 1 DM is changing with many more children diagnosed before developing DKA. We speculate that a new environmental factor(s) may be responsible for the absolute increase in patients presenting without DKA, while older etiologies (both genetic and environmental) are responsible for the steady, unchanging number of patients with a more severe presentation. Greater awareness of diabetes in children is not the factor contributing to earlier diagnosis before DKA develops.

Impaired insulin-mediated glucose uptake in monocytes of short children with intrauterine growth retardation.

AIMS: To determine whether there was an impairment in insulin-mediated glucose uptake in monocytes from short children with intrauterine growth retardation (IUGR) when compared with control subjects. METHODS: Circulating monocytes were isolated by histopaque gradient separation followed by adherence. Monocytes were incubated with insulin at the following concentrations; 0, 0.1, 0.2, 0.6, 1, 2 and 6 nm. 2-deoxyglucose (2-DG) uptake was measured after incubation with [(3)H]2-DG and expressed as pmol/min/10(6) cells. Insulin-stimulated glucose uptake was determined in two ways: 6 nm insulin concentration minus baseline (6-0 nm) and the regression slope of glucose uptake over the range of log insulin concentrations (slope value). Insulin sensitivity was determined from a 90-min frequently sampled intravenous glucose tolerance test with the minimal model. RESULTS: Short children with IUGR (n = 16) had lower slope (4.6 +/- 1.1 vs. 9.5 +/- 2.0, p = 0.002) and 6-0 nm (8 +/- 2 vs. 15 +/- 3 pmol/min/10(6) cells, p = 0.048) glucose uptake values than normal children (n = 11). There was no difference in baseline glucose uptake between IUGR and normal children (36 +/- 5 vs. 48 +/- 7 pmol/min/10(6) cells). In the five subjects with IUGR that were evaluated, the in vivo insulin sensitivity index and glucose effectiveness were found to be positively correlated with insulin-mediated glucose uptake in monocytes (r = 0.54) and baseline glucose uptake in monocytes, respectively (r = 0.69). CONCLUSIONS: Short children with IUGR have impairment in insulin-mediated glucose uptake in monocytes when compared with normal children. Our hitherto limited data indicate that insulin-mediated glucose uptake in monocytes is correlated with in vivo assessment of insulin sensitivity in children with IUGR.

One year follow-up of an emergency department protocol for abused women.

OBJECTIVE: To evaluate if the positive effects of an initially successful emergency department protocol of care for victims of partner abuse (PA) were maintained at one year follow-up. METHOD: A community intervention trial compared two public hospital EDs in Auckland, NZ, at baseline (BL), following implementation of a PA intervention (PI), and at one year follow-up (FU). The initial intervention involved training staff at one ED in a protocol for the identification and acute management of abused women. Later, an on-site protocol co-ordinator worked to ensure that new staff received training in protocol use. Outcomes were assessed by reviewing a random sample of women's medical records. Identification of PA was assessed for each record on a yes/no basis. Identified cases were classified as 'confirmed' or 'suspected' PA. Acute management was assessed by ascertaining staff use of interventions and documentation of abuse. RESULTS: Approximately equal numbers of records were reviewed at each ED at BL, PI and FU (total n = 10,961). Significant interactions were found for classification of PA and acute management offered to victims between EDs over the different study phases. However, the increase in identification of confirmed cases and the improved acute management offered to identified victims found at the intervention ED in the PI phase were not maintained at follow-up. CONCLUSION: Although staff training in the use of protocols for victims of partner abuse can result in improved care, these effects were not maintained. IMPLICATIONS: More intensive institutional efforts are needed if protocol benefits are to be maintained.

Diabetes and obesity in the Louisiana Coushatta Indians.

OBJECTIVE: In order to assist their community in planning intervention and prevention programs, prevalence rates for diabetes and obesity were examined among the Louisiana Coushatta. RESEARCH DESIGN AND METHODS: Coushatta individuals participated in a health survey (questionnaires and physical examinations). Those without known diabetes underwent oral glucose tolerance testing and were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). Those with known DM had the diagnosis confirmed by history and/or elevated hemoglobin A1c. Waist-to-hip ratio (WHR), body mass index (BMI), and percent body fat (%BF) were determined as measures of central adiposity and obesity. Prevalence rates of diabetes and obesity among those examined were calculated. The prevalence of those with more than one anthropometric index positive for obesity was also determined. RESULTS: The prevalence of DM was 30% and IGT was 17% among the first 151 Coushatta participants. For males, the prevalence of obesity was 62%, 57%, and 52%, and for females, 59%, 54%, 45%, as determined by the BMI, %BF, and WHR, respectively. Obesity was more prevalent among those with glucose intolerance (IGT + DM) than those with NGT, and those who were obese had the highest prevalence of glucose intolerance. A greater percentage of those with glucose intolerance had more than one positive obesity measure as compared to those with NGT, and those with more than one index consistent with obesity had a greater prevalence of IGT + DM. CONCLUSIONS: Prevalence rates of DM and obesity are high among the Louisiana Coushatta, and obesity is associated with glucose intolerance. Clustering of the three obesity measures occurs in a high percentage of individuals. Data from the current survey are providing information that is being used by the Coushatta community for health planning and development of intervention and prevention programs.

Outcome evaluation of an emergency department protocol of care on partner abuse.

STUDY OBJECTIVE: To evaluate the impact of a protocol on partner abuse (PA) at increasing identification and improving acute management of abused women by emergency department (ED) staff. METHODS: A community intervention trial compared two public hospital EDs at baseline and following implementation of a PA intervention. The intervention involved training staff at one ED in a protocol for the identification and acute management of abused women. Outcomes were assessed by reviewing a random sample of women's medical records. Identification of PA was assessed for each record on a yes/no basis. Identified cases were classified as 'confirmed' or 'suspected' PA. Acute management was assessed by ascertaining staff documentation of abuse and use of interventions. RESULTS: Approximately equal numbers of records were reviewed at each ED, pre and post implementation (total n = 8,051). Eighty-nine per cent of ED staff were trained. No difference in the overall identification of PA was found (chi 2 = 0.13, p = 0.72), but logistic regression analyses showed other significant changes. At the intervention site, there was an increase in confirmed cases of PA (chi 2 = 7.6, p = 0.006), a trend towards increased documentation (chi 2 = 3.5, p = 0.06) and a significant increase in interventions offered (chi 2 = 13.8, p = 0.002). Changes at the comparison site failed to reach significance. CONCLUSION: Implementation of this protocol resulted in a moderate increase in confirmed cases of abuse and improved the acute management offered to identified victims. The findings reinforce recommendations for widespread implementation of training and protocols to address partner abuse.

Insulin resistance in short children with intrauterine growth retardation.

Epidemiological studies have demonstrated an association between intrauterine growth retardation and an increased risk of adult diseases that include essential hypertension, noninsulin-dependent diabetes mellitus, and ischemic heart disease. A common feature of these diseases is insulin resistance. To investigate whether abnormal insulin sensitivity was a characteristic of subjects with intrauterine growth retardation (IUGR), we compared two groups of short prepubertal children: a group with IUGR (birth weight less than the tenth percentile; n = 15) and a normal birth weight group (n = 12). Subjects underwent a modified frequently sampled iv glucose tolerance test that permitted calculation of the acute insulin response, insulin sensitivity index, and glucose effectiveness. A marked difference in the insulin sensitivity index was noted between groups, with the IUGR group being less insulin sensitive [6.9 vs. 16.9 10(-4)min-1.(microU/mL); P = 0.0048]. The acute insulin response was also significantly different between groups, with IUGR subjects having higher insulin levels (445 vs. 174 microU/mL; P = 0.005). There was no difference in glucose effectiveness between groups. Short prepubertal IUGR children have a specific impairment in insulin sensitivity compared to their normal birth weight peers. In short IUGR children, impaired insulin sensitivity is a potential marker for the early identification and intervention in the development of late adult-onset noninsulin-dependent diabetes mellitus.

Factors predictive of response to growth hormone therapy in Turner's syndrome.

In Turner's syndrome there is marked heterogeneity of growth response to growth hormone (GH) therapy. The study aim was to identify pretreatment factors that influence response to GH therapy. The 70 subjects recruited were prepubertal, had not received sex steroids and had received 28 units/m2/week of GH for > or = 1 year. Pretreatment variables associated with the greatest improvement in height SDS (r2 = 0.58) were weight for length index (p = 0.0001), target height (p = 0.004), bone age delay (p = 0.008) and age (p = 0.04). In conclusion, during two years of GH therapy the best growth response occurred in girls who were younger, heavier, had a delayed bone age and tall parents. Height SDS as a continuous variable is the most effective measure of growth when considering pretreatment factors that may influence response to GH therapy.

Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas. A necropsy study in New Zealand.

Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not individuals at high risk of bowel cancer. Low intracolonic butyrate may be the factor linking the expression of the two types of polyp.

Death in the dental chair.

Death during dental anesthesia is relatively rare. Review of eight such cases which occurred in our county, including the different anesthetics used, revealed one apparent basic pattern that prevailed...a need for awareness that something might go wrong and recognition of the fact that it was going wrong.