A Cochrane review (update 2004): Hylan G-F 20 vs placebo for knee OA

Aim of study: As part of a Cochrane review of viscosupplementation in knee OA, randomised controlled trials (RCT) were reviewed to evaluate evidence for the efficacy of viscosupplementation with Hylan G-F 20 compared to placebo. Methods: Electronic searches were conducted of MEDLINE, EMBASE, Premedline, Current Contents, and CENTRAL. Human, RCT involving Hylan G-F 20 compared to placebo, published prior to 1Q2004, were included. Trials were selected and data extracted by two independent reviewers. Methodological quality was assessed with the Jadad criteria by two reviewers. Data on the OARSI and OMERACT core set clinical outcome measures were extracted where possible. Weighted mean difference (WMD), based on post-test scores, and 95% confidence intervals (CI) were calculated for continuous outcome measures and relative risk (RR) for dichotomous outcome measures. Results: Seven RCT met the inclusion criteria. Median methodological quality was 4 (range 1–5). A further two studies were only reported in abstract form (Jadad score Z 1) and contained insufficient extractable data for inclusion in the analysis. Nine RCT, which compared Hylan G-F 20 to other interventions such as intra-articular corticosteroid, physiotherapy, NSAID, appropriate care, intra-articular gaseous oxygen and other hyaluronan, are not reported here. Twenty-three studies failed to meet inclusion criteria and were excluded. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain on weight-bearing WMD (random effects [RE]) 13 mm on a 0–100 mm VAS (P Z 0.002) based on 6 RCT. This difference was even greater at 5–13 weeks post-injection, 22 m (RE) (P Z 0.001) based on 5 RCT, and at 14–6 weeks postinjection, 21 m (RE) (P Z 0.006) based on 4 RCT. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain at night, WMD 7 mm on a 0–100 mm VAS (P Z 0.003) based on 5 RCT. This difference was even greater at 5–13 weeks post-injection, 11 mm (P Z 0.008) based on 4 RCT, and at 14–26 weeks post-injection, 17 mm (P ! 0.00001) based on 3 RCT. There was no significant difference (WMD 8 mm) between Hylan G-F 20 C oral placebo and arthrocentesis C oral placebo at 5–13 weeks post-injection for WOMAC Pain, but Hylan G-F 20 C oral placebo was more efficacious than arthrocentesis C oral placebo for WOMAC Function, WMD 9 mm on a 0–100 mm VAS (P Z 0.01) (Dickson, 2001). Hylan G-F 20 was more effective than placebo at 1–4 weeks postinjection for the variable designed treatment efficacy, WMD 22 mm on a 0–100 mm VAS (P ! 0.00001) based on improvement in 4 RCT. This difference was even greater at 5–13 weeks post injection, 35 mm (P ! 0.00001). Conclusions: Evidence from this updated Cochrane review supports the superior efficacy of Hylan G-F 20 compared to placebo on weight-bearing pain, night pain, function and treatment efficacy in the treatment of knee OA.

Habitual physical activity and physical activity intensity: their relation to body composition in 5.0-10.5 year old children

Background: Concerns of a decrease in physical activity levels (PALs) of children and a concurrent increase in childhood obesity exist worldwide. The exact relation between these two parameters however has as yet to be fully defined in children. Objective: This study examined the relation in 47 children, aged 5–10.5 y (mean age 8.4plusminus0.9 y) between habitual physical activity, minutes spent in moderate, vigorous and hard intensity activity and body composition parameters. Design: Total energy expenditure (TEE) was calculated using the doubly labelled water technique and basal metabolic rate (BMR) was predicted from Schofield's equations. PAL was determined by PAL=TEE/BMR. Time spent in moderate, vigorous and hard intensity activity was determined by accelerometry, using the Tritrac-R3D. Body fatness and body mass index (BMI) were used as the two measures of body composition. Results: Body fat and BMI were significantly inversely correlated with PAL (r=-0.43, P=0.002 and r=-0.45, P=0.001). Times spent in vigorous activity and hard activity were significantly correlated to percentage body fat (r=-0.44, P=0.004 and r=-0.39, P=0.014), but not BMI. Children who were in the top tertiles for both vigorous activity and hard activity had significantly lower body fat percentages than those in the middle and lowest tertiles. Moderate intensity activity was not correlated with measures of body composition. Conclusions: As well as showing a significant relation between PAL and body composition, these data intimate that there may be a threshold of intensity of physical activity that is influential on body fatness. In light of world trends showing increasing childhood obesity, this study supports the need to further investigate the importance of physical activity for children.

HIV heterogeneity and proximity of homestead to roads in rural South Africa: an exploration using a geographical information system

OBJECTIVE To describe heterogeneity of HIV prevalence among pregnant women in Hlabisa health district, South Africa and to correlate this with proximity of homestead to roads. METHODS HIV prevalence measured through anonymous surveillance among pregnant women and stratified by local village clinic. Polygons were created around each clinic, assuming women attend the clinic nearest their home. A geographical information system (GIS) calculated the mean distance from homesteads in each clinic catchment to nearest primary (1 degrees) and to nearest primary or secondary (2 degrees) road. RESULTS We found marked HIV heterogeneity by clinic catchment (range 19-31% (P < 0.001). A polygon plot demonstrated lower HIV prevalence in catchments remote from 1 degrees roads. Mean distance from homesteads to nearest 1 degrees or 2 degrees road varied by clinic catchment from 1623 to 7569 m. The mean distance from homesteads to a 1 degrees or 2 degrees road for each clinic catchment was strongly correlated with HIV prevalence (r = 0.66; P = 0.002). CONCLUSIONS The substantial HIV heterogeneity in this district is closely correlated with proximity to a 1 degrees or 2 degrees road. GIS is a powerful tool to demonstrate and to start to analyse this observation. Further research is needed to better understand this relationship both at ecological and individual levels, and to develop interventions to reduce the spread of HIV infection.

High HIV incidence and prevalence among young women in rural South Africa: Developing a cohort for intervention trials

Objective: To measure prevalence and model incidence of HIV infection. Setting: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. Methods: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. Results: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. in 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). Conclusions: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.

Variation in mortality rates in Australia: correlation with Indigenous status, remoteness and socio-economic deprivation

Background The aim of this study was to study ecological correlations between age-adjusted all-cause mortality rates in Australian statistical divisions and (1) the proportion of residents that self-identify as Indigenous, (2) remoteness, and (3) socio-economic deprivation. Methods All-cause mortality rates for 57 statistical divisions were calculated and directly standardized to the 1997 Australian population in 5-year age groups using Australian Bureau of Statistics (ABS) data. The proportion of residents who self-identified as Indigenous was obtained from the 1996 Census. Remoteness was measured using ARIA (Accessibility and Remoteness Index for Australia) values. Socioeconomic deprivation was measured using SEIFA (Socio-Economic index for Australia) values from the ABS. Results Age-standardized all-cause mortality varies twofold from 5.7 to 11.3 per 1000 across Australian statistical divisions. Strongest correlation was between Indigenous status and mortality (r = 0.69, p < 0.001). correlation between remoteness and mortality was modest (r = 0.39, p = 0.002) as was correlation between socio-economic deprivation and mortality (r = -0.42, p = 0.001). Excluding the three divisions with the highest mortality, a multiple regression model using the logarithm of the adjusted mortality rate as the dependent variable showed that the partial correlation (and hence proportion of the variance explained) for Indigenous status was 0.03 (9 per cent; p = 0.03), for SEIFA score was -0.17 (3 per cent; p = 0.22); and for remoteness was -0.22 (5 per cent; p = 0.13). Collectively, the three variables studied explain 13 per cent of the variability in mortality. Conclusions Ecological correlation exists between all-cause mortality, Indigenous status, remoteness and disadvantage across Australia. The strongest correlation is with indigenous status, and correlation with all three characteristics is weak when the three statistical divisions with the highest mortality rates are excluded. intervention targeted at these three statistical divisions could reduce much of the variability in mortality in Australia.

Evaluating curriculum changes in undergraduate cancer education

Background. Previous studies have indicated that Australian medical schools have not adequately prepared our graduating doctors to care for patients with cancer. The University of Western Australia (UWA) introduced a two-week clinical attachment in cancer medicine for fifth-year students in 2000 and a four-day clinical attachment in palliative care for sixth-year students in 2001. This article evaluates the introduction of these dedicated clinical attachments in cancer and palliative care. Method. The Australian Cancer Society's Cancer Education Survey was administered to the UWA graduates starting their intern year in teaching hospitals in Perth, Western Australia, in 2002. Their responses were compared with data collected in a similar national survey of Australian and New Zealand interns in 2001. Results. The response rate was 56% (n = 70). When compared with the national data for 2001, more UWA interns (2002) would refer a newly diagnosed breast cancer patient to a multidisciplinary breast clinic (97% vs. 74%, P<.001). Fewer UWA 2002 interns rated their training as poor or very poor in the management of patients with incurable cancer (19% vs. 35%, P=.008) and the management of symptoms in patients dying from cancer (10% vs. 37%, P<.001), but they were more likely to rate their training in assisting a patient to stop smoking as poor or very poor (54% vs. 21%, P<.001). Only a quarter of the UWA 2002 interns had examined a patient with a cancer of the mouth or tongue (25% vs. 49%, P<.001), and only two thirds had examined a patient with lymphoma (64% vs. 83%, P<.001). Conclusions. Our data reflect changes in the final two years of the medical course at UWA and suggest that the introduction of dedicated attachments in cancer and palliative care has better prepared graduating doctors to care for patients with cancer.

The human sulfotransferase SULT1A1 gene is regulated in a synergistic manner by Sp1 and GA binding protein

Human sulfotransferase SULT1A1 is an important phase II xenobiotic metabolizing enzyme that is highly expressed in the liver and mediates the sulfonation of drugs, carcinogens, and steroids. Until this study, the transcriptional regulation of the SULT1A subfamily had been largely unexplored. Preliminary experiments in primary human hepatocytes showed that SULT1A mRNA levels were not changed in response to nuclear receptor activators, such as dexamethasone and 3-methylcolanthrene, unlike other metabolizing enzymes. Using HepG2 cells, the high activity of the TATA-less SULT1A1 promoter was shown to be dependent on the presence of Sp1 and Ets transcription factor binding sites (EBS), located within - 112 nucleotides from the transcriptional start site. The homologous promoter of the closely related SULT1A3 catecholamine sulfotransferase, which is expressed at negligible levels in the adult liver, displayed 70% less activity than SULT1A1. This was shown to be caused by a two-base pair difference in the EBS. The Ets transcription factor GA binding protein (GABP) was shown to bind the SULT1A1 EBS and could transactivate the SULT1A1 promoter in Drosophila melanogaster S2 cells. Cotransfection of Sp1 could synergistically enhance GABP-mediated activation by 10-fold. Although Sp1 and GABP alone could induce SULT1A3 promoter activity, the lack of the EBS on this promoter prevented a synergistic interaction between the two factors. This study reports the first insight into the transcriptional regulation of the SULT1A1 gene and identifies a crucial difference in regulation of the closely related SULT1A3 gene, which accounts for the two enzymes' differential expression patterns observed in the adult liver.

Non-equilibrium energy and momentum accommodation coefficients of Ar atoms scattered from Ni(001) in the thermal regime: A molecular dynamics study

Molecular dynamics simulations are used to study energy and momentum transfer of low-energy Ar atoms scattered from the Ni(001) surface. The investigation concentrates on the dependence of these processes on incident energy, angles of incidence and surface temperature. Energy transfer exhibits a strong dependence on the surface temperature, at incident energies below 500 meV, and incident angles close to specular incidence. Above 500 meV, the surface temperature dependence vanishes, and a limiting value in the amount of energy transferred to the surface is attained. Momentum exchange is investigated in terms of tangential and normal components. Both components exhibit a weak surface temperature dependence, but they have opposite behaviours at all incidence angles. In each component, momentum can be lost or gained following the interaction with the surface. (C) 1997 Elsevier Science B.V.

Determinants of death following burn injury

Background: Burn care has changed considerably. Early surgery, nutritional support, improved resuscitation and novel skin replacement techniques are now well established. The aim of the study was to establish whether changes in management have improved survival following burn injury and to determine the contributory factors leading to non-survival. Methods: This was a retrospective outcome analysis of data collected from a consecutive series of 4094 patients with burns admitted to a tertiary referral, metropolitan teaching hospital between 1972 and 1996, Results: The overall mortality rate was 3.6 per cent. This decreased from 5.3 per cent (1972-1980) to 3.4 per cent (1993-1996) (P = 0.076). The risk of death was increased with increasing burn size (relative risk (RR) 95.90 (95 per cent confidence interval 12.60-729.47) if more than 35 per cent of the total body surface area was burned; P < 0.001) increasing age (RR 7.32 (3.08-17.42) if aged more than 48 years; P < 0.001), inhalation injury (RR 3.61 (2.39-5.47); P < 0.001) and female sex (RR 1.82 (1.23-2.69); P = 0.003). Operative intervention (RR 0.11 (0.06-0.21); P < 0.001) and the presence of an upper limb burn (RR 0.53 (0.35-0.79); P = 0.002) decreased the risk. Conclusion: Modern burn care has decreased the mortality rate. Increasing burn size, increasing age, inhalation injury and female sex increased, while operative intervention and an upper limb burn decreased, the risk of death.

Assault-related admissions to hospital in Central Australia

Objective: To determine the number of assault-related admissions to hospital in the Central Australia region of the Northern Territory over a six-year period. Design and setting: Retrospective analysis of all patients admitted to Alice Springs Hospital (ASH) and Tennant Creek Hospital (TCH) from July 1995 to June 2001, where the primary cause of injury was assault. Main outcome measures: Frequency of assault-related admission to hospital; demographic characteristics of the victims. Results: in the six years, there were 2449 assault-related admissions to ASH and 545 to TCH. Adults aged 25-34 years were most frequently hospitalised for assault, in a proportion greater than their proportion in the NT population, Females represented 59.7% of people admitted to ASH and 54.7% to TCH, greater than their proportion in the NT population. Aboriginals comprised 95.2% of ASH and 89.0% of TCH admissions, and were admitted in a significantly greater proportion than their proportion in the NT population (P < 0.001). The age-adjusted hospital admission rate resulting from assault has increased (P = 0.002) at an average rate of 1.6 (SE, 0.2) per 10 000 people per year. The proportion of assault-related admissions associated with alcohol has also increased significantly (P < 0.001). Conclusion: The frequency of assault-related admissions to hospital, especially among the Aboriginal population, suggests that this major public health issue is escalating.

Exposure to automotive pollution increases plasma susceptibility to oxidation

Low-density lipoprotein oxidation is implicated in the development of atherosclerosis. Plasma susceptibility to oxidation may be used as a marker of low-density lipoprotein oxidation and thus predict atherosclerotic risk. In this study the authors investigated the relationship between plasma susceptibility to oxidation and exposure to automotive pollution in a group of automobile mechanics (n = 16) exposed to high levels of automotive pollution, vs. matched controls (n = 13). The authors induced plasma oxidation by a free radical initiator and they determined susceptibility to oxidation by (1) change in absorbance at 234 nm, (2) lag time to conjugated diene formation, and (3) linear slope of the oxidation curve. Mechanics had significantly higher values (mean standard error) for change in absorbance (1.60 +/- 0.05 vs. 1.36 +/- 0.05; p < .002), and slope (1.6 x 10(-3) +/- 0.1 x 10(-3) vs. 1.3 x 10(-3) +/- 0.1 x 10(-3); p < .001), compared with controls. These results indicate that regular exposure to automotive pollutants increases plasma susceptibility to oxidation and may, in the long term, increase the risk of developing atherosclerosis.

Transition to raloxifene with and without low-dose estrogen therapy in postmenopausal women: effects on serum lipids and fibrinogen - a pilot study

Objective To compare the effects of transferring from low-dose transdermal estrogen to raloxifene (RLX), with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, on serum lipids and fibrinogen in postmenopausal women previously administered estrogen plus progestogen therapy. Methods Sixty postmenopausal women (mean age 55 years) were randomized to one of two treatment groups: RLX + low-dose transdermal estrogen (RLX + E) or RLX + placebo. The study consisted of four 8-week phases: phase I (all subjects low-dose transdermal estrogen 25 mug/day), phase II (double-blind RLX 60 mg every 2nd day in combination with either low-dose transdermal estrogen or placebo), phase III (all subjects RLX 60 mg every 2nd day + placebo) and phase IV (all subjects RLX 60 mg/day + placebo). Results No significant differences existed between groups for baseline measurements prior to phase I. In phase I, for all subjects combined, total cholesterol and low-density lipoprotem cholesterol both showed a significant increase (median increase of 0.2 mmol/l, p = 0.008 and 0.4 mmol/l, p < 0.001, respectively), while triglycerides decreased significantly (median decrease of 0.2 mmol/l, p < 0.001). For the primary analysis (phase II to phase IV), the mean change from baseline observations showed no significant differences between the therapy groups for serum lipids, fibrinogen, vital signs or weight. In the comparison phase (phase II), changes in serum lipids, fibrinogen, vital signs and weight were not significantly different between groups. Conclusion Gradual conversion to RLX from low-dose transdermal estrogen, with a phase of alternate-day RLX therapy with or without low-dose transdermal estrogen, does not have any effect on the serum lipid profile or fibrinogen level.