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Rheumatoid arthritis (RA) is known to increase the risk of cardiovascular (CV) disease. However, the individual impact of traditional CV risk factors in RA is unknown. To assess the strength of the association between individual CV risk factors and rate of either myocardial infarction (MI), combined CV morbidity (MI, angina pectoris, heart failure, stroke, and peripheral arterial disease (PAD)) or CV mortality in RA patients. RA studies reporting traditional CV risk factors [hypertension, type 2 diabetes (T2D), smoking, hypercholesterolaemia, obesity, and physical inactivity] as exposures and MI, CV morbidity (MI, angina, heart failure, stroke, and PAD combined) or CV mortality alone as outcomes were searched until March 2013 using MEDLINE, Scopus and Cochrane. Meta-analyses combined relative risk (RR) estimates from each study where either the RR and 95% confidence intervals or where raw counts were available. Ten studies reporting sufficient data for inclusion into meta-analyses were identified. Relevant data was available for each risk factor and MI and CV morbidity but no studies reported on CV mortality. Risk of MI increased in RA patients with hypertension (RR 1.84, 95% CI 1.38, 2.46) and T2D (RR 1.89, 95% CI 1.36, 2.63). CV morbidity increased with hypertension (RR 2.24, 95% CI 1.42, 3.06), T2D (RR 1.94, 95% CI 1.58, 2.30), smoking (RR 1.50, 95% CI 1.15, 1.84), hypercholesterolaemia (RR 1.73, 95% CI 1.03, 2.44) and obesity (RR 1.16, 95% CI 1.03, 1.29) but not with physical inactivity (RR 1.00, 95% CI 0.71, 1.29). Hypertension, T2D, smoking, hypercholesterolaemia and obesity increased CV risk in patients with RA. These results highlight the importance of managing CV risk factors in RA, similarly to non-RA patients.

BACKGROUND Endothelial nitric oxide (NO) is fundamental to cardiovascular health. Dietary nitrate and nitrate from endothelial derived NO metabolism provides a significant contribution to the circulating NO pool through the nitrate–nitrite–NO pathway. A critical step in this pathway is the reduction of nitrate to nitrite by the oral microbiota. We aimed to assess the effects of antibacterial mouthwash use on markers of nitrate–nitrite–NO metabolism and blood pressure in treated hypertensive men and women. METHODS Fifteen treated hypertensive men and women (mean age 65 years) were recruited to a randomized controlled cross-over trial. The effects of 3-day use of antibacterial mouthwash on oral nitrate to nitrite reduction, salivary and plasma nitrate and nitrite, plasma cyclic guanosine monophosphate (cGMP) and systolic and diastolic blood pressure were compared to control (water). RESULTS Relative to control, 3-day antibacterial mouthwash use resulted in decreased oral nitrate to nitrite reduction (P = 0.02), decreased salivary nitrite (P = 0.01) and increased salivary nitrate (P < 0.001), and there was a trend toward a decrease in plasma nitrite concentration (P = 0.09). Use of antibacterial mouthwash over 3 days also resulted in higher systolic blood pressure (2.3mm Hg; 95% CI: 0.5, 4.0; P = 0.01), but not diastolic blood pressure (P = 0.4) or plasma cGMP (P = 0.7), relative to control. CONCLUSIONS Interruption of the nitrate–nitrite–NO pathway through the use of antibacterial mouthwash was paralleled by a small elevation of systolic blood pressure in treated hypertensive men and women.

Background The Human T Lymphotropic Virus type 1 (HTLV-1) subtype C is endemic to central Australia where each of the major sequelae of HTLV-1 infection has been documented in the socially disadvantaged Indigenous population. Nevertheless, available epidemiological information relating to HTLV-1c infection is very limited, risk factors for transmission are unknown and no coordinated program has been implemented to reduce transmission among Indigenous Australians. Identifying risk factors for HTLV-1 infection is essential to direct strategies that could control HTLV-1 transmission. Methods Risk factors for HTLV-1 infection were retrospectively determined for a cohort of Indigenous Australians who were tested for HTLV-1 at Alice Springs Hospital (ASH), 1st January 2000 to 30th June 2013. Demographic details were obtained from the ASH patient management database and the results of tests for sexually transmitted infections (STI) were obtained from the ASH pathology database. Results Among 1889 Indigenous patients whose HTLV-1 serostatus was known, 635 (33.6 %) were HTLV-1 Western blot positive. Only one of 77 (1.3 %) children tested was HTLV-1 infected. Thereafter, rates progressively increased with age (15–29 years, 17.3 %; 30–49 years, 36.2 %; 50–64 years, 41.7 %) reaching 48.5 % among men aged 50–64 years. In a multivariable model, increasing age (OR, 1.04; 95 % CI, 1.03–1.04), male gender (OR, 1.41; 95 % CI, 1.08–1.85), residence in the south (OR, 10.7; 95 % CI, 7.4–15.6) or west (OR, 4.4; 95 % CI, 3.1–6.3) of central Australia and previous STI (OR, 1.42; 95 % CI, 1.04–1.95) were associated with HTLV-1 infection. Infection was acquired by three of 351 adults who were tested more than once during the study period (seroconversion rate, 0.24 (95 % CI = 0.18–2.48) per 100 person-years). Conclusions This study confirms that HTLV-1 is highly endemic to central Australia. Although childhood infection was documented, HTLV-1 infection in adults was closely associated with increasing age, male gender and STI history. Multiple modes of transmission are therefore likely to contribute to high rates of HTLV-1 infection in the Indigenous Australian population. Future strategies to control HTLV-1 transmission in this population require careful community engagement, cultural understanding and Indigenous leadership.

The impact of antenatal depression on pregnancy outcomes has been well investigated in developed countries, but few studies have been conducted in low-income countries. As depression is significantly affected by socio-economic and cultural factors, it would be difficult to generalize evidence from high-income countries to low-income countries. We conducted a community-based cohort study to estimate the incidence of adverse birth outcomes and the direct and indirect pathways via which depression and other psychosocial risk factors may impact such birth outcomes within Gondar town, Ethiopia. The study followed 916 pregnant women who were screened for antenatal depression using the Edinburgh Postnatal Depression Scale (EPDS). We also assessed the incidence of preterm births, Low Birth Weight (LBW) and stillbirths. Modified Poisson regression was used to estimate the relative risk of predictors on adverse birth outcomes and a Generalized Structural Equation Model (GSEM) was used to estimate the direct and indirect effect of antenatal depression and other psychological risk factors on adverse birth outcomes. The cumulative incidence of stillbirth, LBW and preterm was 1.90%, 5.25%, and 16.42%, respectively. The risk of preterm birth was 1.61, 1.46, 1.49, and 1.77 times higher among participants who identified as Muslim, reported being fearful of delivery, were government employee's, and who had no antenatal care services, respectively. Partner support moderated the association between depression, preterm birth, and LBW. Depression had no direct effect on birth outcomes but indirectly affected preterm birth via partner support. Religion had both direct and indirect effects on preterm birth, while occupation and fear of delivery had direct effects. The risk of LBW was 9.44 and 2.19 times higher among preterm births and those who had exposure to tobacco, respectively. Stress coping was indirectly associated, and preterm birth and tobacco exposure were directly associated with LBW. The risk of stillbirth was 3.22 times higher in women with antenatal depression and 73% lower in women with higher coping abilities. There was a high incidence of all adverse birth outcomes in Gondar Town. Depression and psychosocial risk factors had important indirect negative effects on risk, while partner support provided a positive indirect effect on the incidence of adverse birth outcomes. Interventions that focus on increasing partner engagement and participation in antenatal support may help reduce adverse birth outcomes by enhancing maternal resilience.

The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.

Admission to hospital introduces risks for people with Parkinson's disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual's symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome. To determine the occurrence and identify factors that contribute to Parkinson's medication errors in Australian hospitals. A retrospective discharge diagnosis code search identified all admissions for people with Parkinson's disease to three tertiary metropolitan hospitals in South Australia, Australia over a 3-year period. Of the 405 case notes reviewed 351 admissions met our inclusion criteria. Medication prescribing (30.5%) and administration (85%) errors during admission were extremely common, with the most frequent errors related to administration of levodopa preparations (83%). A higher levodopa equivalent dosage, patients with a modified swallowing status or nil by mouth order during admission, and patients who did not have a pharmacist led medication history within 24 hours of admission had significantly higher rates of medication errors. This study identified 3 major independent factors that increased the risk of errors during medication management for people with Parkinson's disease during hospitalization. Thus, targeting these areas for preventative interventions have the greatest chance of producing a clinically meaningful impact on the number of hospital medication errors occurring in the Parkinson's population.

Studies examining the association between obesity and mortality in cardiac arrest patients have been conflicting which might either be due to residual confounding, or a reliance on estimating the conditional effects rather than the marginal (causal) effects of obesity. We estimated the conditional and causal effects of obesity on mortality in cardiac arrest patients using the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD). This retrospective registry-based cohort study from ICUs of Australia and New Zealand included all ICU patients admitted with cardiac arrest between 2010 and 2020 with height and weight data recorded. The conditional and marginal effects of obesity on mortality was estimated using multivariate binary logistic regression and Targeted Maximum Likelihood Estimation (TMLE) respectively. The primary outcome was in-hospital mortality. A total 13,970 patients had complete data and were available for analysis. In multivariate binary logistic regression, there was no difference in the odds of in-hospital mortality for the obese versus non-obese groups; adjusted OR = 0.95, 95% CI = 0.87–1.03; p 0.25. Results were similar using TMLE (Marginal OR= 0.97; 95% CI = 0.91–1.02, p = 0.62). After adjustment, there was no association between obesity and outcomes in cardiac arrest patients admitted to ICU. •Previously observed obesity paradox in cardiac arrest patient might be due to use of conditional methods of epidemiology.•Targeted maximum likelihood estimation (TMLE) is a doubly robust method to provide an unbiased estimate of causal effects.•There was no difference in the ICU and in-hospital mortality between obese and non-obese groups.

In 2013, the Indonesian government launched the strategic use of antiretroviral therapy (SUFA) initiative with an aim to move closer to achieving the UNAIDS 90-90-90 target. This study assessed the impact of SUFA on the cascade of HIV care. We performed a two-year retrospective population-based cohort study of all HIV positive individuals aged [greater than or equal to] 18 years residing in two cities where SUFA was operational using data from HIV clinics. We analysed data for one-year pre- and one-year post-SUFA implementation. We assessed the rates of enrolment in care, assessment for eligibility for antiretroviral therapy (ART), treatment initiation, loss to follow-up (LTFU) and mortality. Multivariate Cox regression was used to determine the pre-to-post-SUFA hazard ratio. A total of 2,292 HIV positive individuals (1,085 and 1,207 pre and post-SUFA respectively) were followed through their cascade of care. In the pre-SUFA period, 811 (74.6%) were enrolled in care, 702 (86.6%) were found eligible for ART, 485 (69.1%) initiated treatment, 102 (21%) were LTFU and 117 (10.8%) died. In the post-SUFA period, 930 (77%) were enrolled in care, 896 (96.3%) were found eligible for ART, 627 (70%) initiated treatment, 100 (16%) were LTFU and 148 (12.3%) dead. There was an 11% increase in the rate of HIV linkage to care (HR = 1.11; 95% CI 1.001, 1.22 p<0.05), a 13% increase in the rate of eligibility for ART (HR = 1.13, 95% CI 1.02,1.25, p<0.01) and a 27% reduction in LTFU (HR = 0.73, 95%CI 0.55, 0.97, p<0.05). Rates of ART initiation and mortality did not change. SUFA was effective in improving HIV care in relation to linkage to care, eligibility and ART retention. Therefore, the scale up across the whole of Indonesia of the SUFA currently in the form of a test and treat policy, with improvement in testing and treatment strategies is justified.

Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1 ppm selenium as selenium-enriched milk protein, or combination of 1 ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ß-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P<0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P<0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ß-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.

► Randomized clinical trial of a novel adjuvanted H1N1/2009 pandemic influenza vaccine. ► Reports first pandemic use of a vaccine based on recombinant hemagglutinin. ► The recombinant vaccine was produced within 12 weeks of the pandemic. ► Advax™, a novel polysaccharide adjuvant, significantly improved vaccine responses. Timely vaccine supply is critical during influenza pandemics. A recombinant hemagglutinin (rHA)-based vaccine could overcome production hurdles of egg-based vaccines but has never previously been tested in a real-life pandemic setting. The primary aim was to determine the efficacy of a recombinant pandemic vaccine and whether its immunogenicity could be enhanced by a novel polysaccharide adjuvant (Advax™). 281 adults aged 18–70 years were recruited in a randomized, subject and observer blinded, parallel-group study of rHA H1N1/2009 vaccine with or without adjuvant. Immunizations were at 0 and 3 weeks with rHA 3, 11 or 45μg. Serology and safety was followed for 6 months. At baseline, only 9.1% of subjects (95% CI: 6.0–13.2) had seroprotective H1N1/2009 titers. Seroconversion rates varied by rHA dose, presence of adjuvant, subject age and number of immunizations. Eighty percent (95% CI: 52–96) of 18–49 year olds who received rHA 45μg with adjuvant were seroprotected at week 3, representing a 11.1-fold increase in antibody titers from baseline. Advax™ adjuvant increased seroprotection rates by 1.9 times after the first, and 2.5 times after the second, immunization when compared to rHA alone. Seroprotection was sustained at 26 weeks and the vaccine was well tolerated with no safety issues. The study confirmed the ability to design, manufacture, and release a recombinant vaccine within a short time from the start of an actual influenza pandemic. Advax™ adjuvant significantly enhanced rHA immunogenicity.