Insights into the clinical management of the syndrome of supine hypertension--orthostatic hypotension (SH-OH): the Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Our previously proposed morphological classification of orthostatic hypotension (MOH) is an approach to the definition of three typical orthostatic hemodynamic patterns using non-invasive beat-to-beat monitoring. In particular, the MOH pattern of large drop/non-recovery (MOH-3) resembles the syndrome of supine hypertension-orthostatic hypotension (SH-OH), which is a treatment challenge for clinicians. The aim of this study was to characterise MOH-3 in the first wave of The Irish Longitudinal Study of Ageing (TILDA), with particular attention to concurrent symptoms of orthostatic intolerance (OI), prescribed medications and association with history of faints and blackouts. METHODS: The study included all TILDA wave 1 participants who had a Finometer® active stand. Automatic data signal checks were carried out to ensure that active stand data were of sufficient quality. Characterisation variables included demographics, cardiovascular and neurological medications (WHO-ATC), and self-reported information on comorbidities and disability. Multivariable statistics consisted of logistic regression models. RESULTS: Of the 4,467 cases, 1,456 (33%) were assigned to MOH-1 (small drop, overshoot), 2,230 (50%) to MOH-2 (medium drop, slower but full recovery), and 781 (18%) to MOH-3 (large drop, non-recovery). In the logistic regression model to predict MOH-3, statistically significant factors included being on antidepressants (OR = 1.99, 95% CI: 1.50 - 2.64, P < 0.001) and beta blockers (OR = 1.60, 95% CI: 1.26 - 2.04, P < 0.001). MOH-3 was an independent predictor of OI after full adjustment (OR = 1.47, 95% CI: 1.25 - 1.73, P < 0.001), together with being on hypnotics or sedatives (OR = 1.83, 95% CI: 1.31 - 2.54, P < 0.001). In addition, OI was an independent predictor of history of falls/blackouts after full adjustment (OR = 1.27, 95% CI: 1.09 - 1.48, P = 0.003). CONCLUSIONS: Antidepressants and beta blockers were independently associated with MOH-3, and should be used judiciously in older patients with SH-OH. Hypnotics and sedatives may add to the OI effect of MOH-3. Several trials have demonstrated the benefits of treating older hypertensive patients with cardiovascular medications that were not associated with adverse outcomes in our study. Therefore, the evidence of benefit does not necessarily have to conflict with the evidence of potential harm

Functional central limit theorems for vicious walkers

We consider the diffusion scaling limit of the vicious walker model that is a system of nonintersecting random walks. We prove a functional central limit theorem for the model and derive two types of nonintersecting Brownian motions, in which the nonintersecting condition is imposed in a finite time interval $(0,T]$ for the first type and in an infinite time interval $(0,\infty)$ for the second type, respectively. The limit process of the first type is a temporally inhomogeneous diffusion, and that of the second type is a temporally homogeneous diffusion that is identified with a Dyson's model of Brownian motions studied in the random matrix theory. We show that these two types of processes are related to each other by a multi-dimensional generalization of Imhof's relation, whose original form relates the Brownian meander and the three-dimensional Bessel process. We also study the vicious walkers with wall restriction and prove a functional central limit theorem in the diffusion scaling limit.Comment: AMS-LaTeX, 20 pages, 2 figures, v6: minor corrections made for publicatio

Colorectal cancer metastatic disease progression in Australia: a population-based analysis

No previous Australian population-based studies have described or quantified the progression of colorectal cancer (CRC) to metastatic disease. We describe patterns of progression to metastatic disease for an Australian cohort diagnosed with localised or regional CRC.All localised and regional CRC cases in the New South Wales Cancer Registry diagnosed during 2000-2007 were followed to December 2011 for subsequent metastases (identified by subsequent disease episode notifications) or CRC death. Cox regression was used to identify factors associated with metastatic progression.After a median 5.3 years follow-up, 26.4% of the 12757 cases initially diagnosed with localised or regional colon cancer had developed metastatic disease, as had 29.5% of the 7154 rectal cancer cases. For both cancer sites, risk of metastatic progression was significantly higher for those initially diagnosed with regional disease (adjusted hazard ratio [aHR] 3.49 for colon, 2.66 for rectal cancer), and for older cases (e.g. aHR for >79years vs <60years: 1.38 for colon, 1.69 for rectal cancer). Risk of disease progression was significantly lower for females, and varied by histology type. For colon cancer, the risk of disease progression decreased over time. For rectal cancer, risk of metastatic progression was significantly higher for those living in more socioeconomically disadvantaged areas compared with those in the least disadvantaged area.An understanding of the variation in risk of metastatic progression is useful for planning health service requirements, and can help inform decisions about treatment and follow-up for colorectal cancer patients

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

&lt;p&gt;Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.&lt;/p&gt

Estimating prevalence of distant metastatic breast cancer: a means of filling a data gap

PURPOSE: To develop and validate a method for estimating numbers of people with distant cancer metastases, for evidence-based service planning. METHODS: Estimates were made employing an illness-death model with distant metastatic cancer as the illness state- and site-specific mortality as an outcome, using MIAMOD software. To demonstrate the method, we estimated numbers of females alive in Australia following detection of distant metastatic breast cancer during 1980-2004, using data on patient survival from an Australian population-based cancer registry. We validated these estimates by comparing them with direct prevalence counts. RESULTS: Relative survival at 10 years following detection of distant metastases was low (5-20 %), with better survival experienced by: (1) females where distant metastatic disease was detected at initial diagnosis rather than subsequently (e.g., at recurrence); (2) those diagnosed in more recent calendar years; and (3) younger age groups. For Australian females aged less than 85 years, the modeled cumulative risk of detection of distant metastatic breast cancer (either at initial diagnosis or subsequently) declined over time, but numbers of cases with this history rose from 71 per 100,000 in 1980 to 84 per 100,000 in 2004. The model indicated that there were approximately 3-4 prevalent distant metastatic breast cancer cases for every breast cancer death. Comparison of estimates with direct prevalence counts showed a reasonable level of agreement. CONCLUSIONS: The method is straightforward to apply and we recommend its use for breast and other cancers when registry data are insufficient for direct prevalence counts. This will provide estimates of numbers of people who would need ongoing medical surveillance and care following detection of distant metastase

The Silences Framework: A Method for researching sensitive themes and marginalized health perspectives (English version)

Objective: To describe the experience of applying of The Silences Framework to underpin health research investigating Tuberculosis/HIV/AIDS coinfection . Method: The Silences Framework originally developed following a study exploring the decisions and silences surrounding black Caribbean men living in England, discussing the themes 'sexual health' and 'ethnicity'. Following this study a conceptual a theory for research on sensitive issues and health care of marginalized populations was developed called 'Screaming Silences' which forms the foundation of The Silences Framework. Screaming Silences define research areas and experiences that are poorly studied, little understood or silenced. Results: The Silences Framework supports researchers in revealing "silences" in the subjects they study - as such results may reflect how beliefs, values, and experiences of some groups influence their health. This framework provides the application of four complementary stages: working the silences, hearing silences, voicing silences and working with the silences. The analysis occurs cyclically and can be repeated as long as the silences inherent in a study are not revealed. Conclusion: this article presents The Silences Framework and the application of the notion of "sounds of silence", mapping an antiessentialist theoretical framework for its use in sensitive research in health and nursing areas, being a reference for other researchers in studies involving marginalized populations. KEYWORDS: Inequalities in health. Methods. Nursing. Coinfection. Research. Tuberculosis. Acquired immunodeficiency syndrome

Contrasting temporal trends in lung cancer incidence by socioeconomic status among women in New South Wales, Australia, 1985-2009

OBJECTIVE: We examined long-term trends in lung cancer incidence for women by socioeconomic groups in New South Wales (NSW), Australia. METHODS: Data on lung cancer incidence for women were extracted from the NSW Cancer Registry database. We divided the study cohort into five quintiles according to an area-based index of education and occupation (IEO) and calculated annual age-standardised incidence rates by IEO quintile for the period 1985-2009. The age-standardised incidence ratio (SIR) was estimated for IEO quintiles and 5-year period of diagnosis using the highest IEO quintile as the reference. RESULTS: Overall, lung cancer incidence for women aged 25-69 years increased gradually from 19.8 per 100,000 in 1985 to 25.7 per 100,000 in 2009. The trends by IEO quintile were somewhat comparable from 1985 through to 1995, but from then on rates remained relatively stable for women residing in the highest quintile while increasing for women residing in the remaining four quintiles. Consequently, the SIR for all four of the lower IEO quintiles increased significantly over the 25-year period. For example, the SIR in the lowest IEO quintile increased from 1.16 (95% CI, 0.99-1.37) during 1985-1989 to 1.70 (95% CI, 1.50-1.93) during 2005-2009. The corresponding estimates for women aged 70 years or older showed no clear pattern of socioeconomic gradient. CONCLUSION: The increasing gap in lung cancer incidence between women in the highest socioeconomic group and all others suggests that there is a continued need for the broad implementation of tobacco control interventions, so that smoking prevalence is reduced across all segments of the population and the subsequent benefits are shared more equitably across all demographic groups

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Increased risk of suicide in New South Wales men with prostate cancer: Analysis of linked population-wide data

© 2018 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background An elevated risk of suicide after a diagnosis of prostate cancer has been reported previously in the USA and Sweden. We aimed to identify whether prostate cancer survivors resident in New South Wales Australia are at higher risk of suicide and if so, who is most at risk. Methods Data were obtained from the New South Wales (NSW) Cancer Registry for all men diagnosed with prostate cancer in NSW during 1997 to 2007. These were linked by the Centre for Health Record Linkage (CHeReL) to Australian Bureau of Statistics Mortality Data to the end of 2007 to determine vital status and cause of death. We compared the number of suicides observed for prostate cancer survivors with the expected number of suicides based on age- and calendar year- specific rates for the NSW Male population using standardised mortality ratios (SMRs). Suicide rate ratios (RR) by disease and patients' characteristics were estimated using multivariable negative binomial regression to determine the most at risk groups. Results During the study period 51,924 NSW men were diagnosed with prostate cancer. Forty nine of these men were subsequently recorded as committing suicide up to 10 years after diagnosis with an SMR of 1.70 (95% CI:1.26±2.25). Twenty six (53%) of these suicides occurred within 12 months after diagnosis. Risk diminished over time since diagnosis (RR in 1±2 years after diagnosis = 0.29, 95% CI: 0.12±0.71, 2±4 years RR = 0.30, 95% CI: 0.14±0.16 and 4+ years RR = 0.26, 95% CI: 0.11±0.60 compared with <1 year since diagnosis). Men with non-localised disease had a higher risk of suicide compared to men with localised disease (RR = 2.68, 95% CI: 1.15±6.23). Men living outside major cities had lower risk of suicide compared to those resident in major cities (rate ratio = 0.42, 95% CI: 0.20±0.87). Single, divorced, widowed or separated men were more likely to commit suicide than married men (RR = 4.18, 95% CI: 2.36±7.42). Conclusion Risk of suicide is higher for NSW men diagnosed with prostate cancer than the general age matched Male population. Vulnerable or lonely men and those with pre-existing depression or suicidal ideation who are diagnosed with prostate cancer should be offered additional psychological support