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Thompson, Sandra C., Gill E. Checkley, Jane S. Hocking, Nick Crofts, Anne M. Mijch, and Fiona K. Judd. "HIV Risk Behaviour and HIV Testing of Psychiatric Patients in Melbourne." Australian & New Zealand Journal of Psychiatry 31, no. 4 (August 1997): 566–76. http://dx.doi.org/10.3109/00048679709065079.
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Objectives: Patients with chronic mental illnesses constitute an important risk group for HIV infection overseas. This study aimed to determine the prevalence of risk behaviours associated with HIV transmission and factors associated with HIV testing in psychiatric patients in Melbourne. Methods: Inpatients and outpatients completed an interviewer-administered questionnaire which covered demographics, psychiatric diagnosis, risk behaviour, and HIV education and testing. Results: Of 145 participants, 60% were male and 55.2% had schizophrenia. Injecting drug use (IDU) was reported by 15.9%, a figure approximately 10 times that found in other population surveys. Most patients reported sex in the last decade and over 20% had multiple sexual partners in the last year. Of males, 12.6% reported sex with another male (9.2% anal sex); 19.0% of females reported sex with a bisexual male. Nearly half of the males reported sex with a prostitute, 2.5 times that in a population sample. Only 15.9% reported ever having someone talk to them specifically about HIV and its transmission, although one-third had been tested for HIV. In multivariate analysis, male-male sex, paying for sex, and IDU were associated with HIV testing, but those whose primary language was not English were less likely to be tested. Those who had received HIV education were more likely to have used a condom last time they had sex (OR 4.52, 95%C11.49–14.0). Conclusions: This study provides evidence that those with serious mental illness in Victoria have higher rates of participation in risk behaviour for HIV infection than those in the general community. Attention to HIV education and prevention in this group has been inappropriately scant; strategies to encourage safer behaviour are urgently needed.
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Kong, Fabian Y. S., Jane S. Hocking, Chris Kyle Link, Marcus Y. Chen, and Margaret E. Hellard. "Sex and sport: sexual risk behaviour in young people in rural and regional Victoria." Sexual Health 7, no. 2 (2010): 205. http://dx.doi.org/10.1071/sh09071.
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Background: To determine the prevalence of chlamydia and understand sexual risk behaviour in 16–29 year olds in rural Victoria through a chlamydia testing program undertaken at local sporting clubs. Methods: Young people were recruited from the Loddon Mallee region of Victoria, Australia between May and September 2007. After a night of sporting practice, participants provided a first pass urine sample and completed a brief questionnaire about sexual risk behaviour. Those positive for chlamydia were managed by telephone consultation with a practitioner from Melbourne Sexual Health Centre. Results: A total of 709 young people participated (77% male, 23% female) in the study; 77% were sexually active. Overall chlamydia prevalence in sexually active participants was 5.1% (95% confidence interval [CI]: 3.4–7.3); 7.4% in females (95% CI: 3.5–13.6) and 4.5% in males (95% CI: 2.7–6.9). Approximately 60% of males and 20% of females consumed alcohol at high ‘Risky Single Occasion Drinking’ levels at least weekly and 60% had used an illicit drug in their lifetime. Nearly 45% reported having sex in the past year when they usually wouldn’t have because they were too drunk or high. Sexually transmissible infection (STI) knowledge was generally poor and only 25% used a condom the last time they had sex. Conclusion: Chlamydia prevalence was high in our study population. Many participants had poor knowledge about STIs and low condom use. These findings combined with high levels of risky alcohol use and having sex while intoxicated highlights the need for programs in rural and regional Victoria that combine both STI testing and prevention and education programs.
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Ponsford, Jennie, John Olver, Michael Ponsford, and Michael Schönberger. "Two-Year Outcome Following Traumatic Brain Injury and Rehabilitation: A Comparison of Patients From Metropolitan Melbourne and Those Residing in Regional Victoria." Brain Impairment 11, no. 3 (December 1, 2010): 253–61. http://dx.doi.org/10.1375/brim.11.3.253.
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AbstractBackground and Objective:Victoria's trauma management system provides acute care and rehabilitation following traumatic brain injury (TBI), with care of more complex injuries generally provided in specialist centres in metropolitan Melbourne. Little is known about how the outcomes of TBI survivors living in metropolitan Melbourne compare to those who reside in regional Victoria once they return to their community, where support services may be less available. The aim of the present study was to compare, in TBI individuals who have been treated at an inner-city rehabilitation centre in Melbourne, the long-term outcomes of those who live in metropolitan Melbourne (termed ‘Metro’) with those who reside in regional Victoria, termed ‘Regional.’Design and participants:Comparative study with quantitative outcome measures. A total of 959 patients, of whom 645 were designated ‘metro’ and 314 ‘regional’, were followed-up routinely at 2 years post-injury.Outcome measures:Structured Outcome Questionnaire, Glasgow Outcome Scale — Extended, Sickness Impact Profile, Craig Handicap Assessment and Reporting Technique, Hospital Anxiety and Depression Scale, Alcohol Use Disorders Identification Test and Drug Abuse Screening Test.Results:Few differences in outcomes were found between groups. However, after controlling for group differences in age and injury severity, some non-significant trends were suggestive of better outcomes in terms of less social isolation and anxiety and fewer dysexecutive behaviours in regional dwellers.Conclusions:These findings suggest that outcomes in patients from regional areas are at least as good as those from metropolitan Melbourne.
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Hocking, Jane S., Jessika Willis, Sepehr Tabrizi, Christopher K. Fairley, Suzanne M. Garland, and Margaret Hellard. "A chlamydia prevalence survey of young women living in Melbourne, Victoria." Sexual Health 3, no. 4 (2006): 235. http://dx.doi.org/10.1071/sh06033.
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Background: To estimate the population-based chlamydia prevalence among women aged 18 to 35 years living in Melbourne, Victoria, and to assess the feasibility of using mailed urine specimens to test women. Methods: A simple random sample of 11 001 households in Melbourne was selected from the telephone directory. Participants completed telephone interviews and provided urine specimens through the mail for chlamydia testing. Urines were tested using polymerase chain reaction. Results: 11 001 households were contacted, with 1532 households identified as including eligible women; telephone interviews were completed, with 979 women giving a response rate of 64%. Six hundred and fifty-seven women provided a urine specimen with a response rate of 43%. Among sexually active women aged 18–24 years, the chlamydia prevalence was 3.7% (95% CI: 1.2%, 8.4%) and 0.2% (95% CI: 0.0%, 1.1%) among 25–35 year olds. Chlamydia prevalence increased significantly with an increasing number of male sexual partners. Conclusions: This is the first study of its kind in Australia and shows that chlamydia prevalence increases with an increasing number of male sexual partners in the last 12 months. Mailed urine specimens are feasible for conducting population-based chlamydia-prevalence surveys but it is difficult to obtain high response rates with this methodology. Public health resources should now be directed towards investigating how to reach young women at increased risk of infection, ensuring that they are tested for chlamydia.
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Guy, Rebecca, Megan S. C. Lim, Yung-Hsuan J. Wang, Nicholas Medland, Jonathan Anderson, Norman Roth, and Margaret E. Hellard. "A new surveillance system for monitoring HIV infection in Victoria, Australia." Sexual Health 4, no. 3 (2007): 195. http://dx.doi.org/10.1071/sh07011.
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Objectives: To establish a new mechanism for monitoring patterns of HIV infection, in the context of a sustained increase in HIV diagnosis among men who have sex with men (MSM) in Victoria. Methods: Between April 2004 and August 2005, a linked voluntary HIV sentinel surveillance system was implemented at five medical clinics with a high case load of MSM. Using a questionnaire, doctors collected HIV testing history, demographic and sexual risk behaviour information from all clients undergoing voluntary HIV testing. Questionnaires were linked with HIV test results. Logistic regression analysis was conducted to determine factors associated with HIV infection. Results: Of 3435 MSM tested for HIV at participating sites, 1.7%, (95% CI = 1.2–2.2) were newly diagnosed with HIV; between 2004 and 2005 the proportion increased from 1.3% (95% CI = 1.2–1.5) to 2.0% (95% CI = 1.8–2.2), P = 0.107. There was no significant change in the number of HIV tests conducted per month or in demographic characteristics, testing history and sexual behaviour characteristics between time periods. In multivariate analysis, reporting unprotected anal intercourse (UAI) with any partner, UAI with a HIV-positive partner/s and being aged 30–39 years or 40 years or greater were significantly associated with HIV infection. Conclusion: This new surveillance mechanism, based on linked testing at participating clinics, indicates that the increase in HIV notifications in 2005 was unrelated to changes in testing and data from a Melbourne sexual behavioural survey suggests the increase was more likely to be attributed to increases in transmission within the past few years. The sentinel system highlighted UAI, especially with HIV positive partner/s are important transmission factors.
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Wilson, Laura Ann. "Perceptions of Legitimacy and Strategies of Resistance: Melbourne Illicit Drug Users and Random Roadside Drug Testing." Current Issues in Criminal Justice 23, no. 2 (November 2011): 183–201. http://dx.doi.org/10.1080/10345329.2011.12035918.
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Cameron, Max, Stuart Newstead, Belinda Clark, and Luke Thompson. "Evaluation of an Increase in Roadside Drug Testing in Victoria Based on Models of the Crash Effects of Random and Targeted Roadside Tests." Journal of Road Safety 33, no. 2 (May 1, 2022): 17–32. http://dx.doi.org/10.33492/jrs-d-20-00272.
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Drug driving continues to be overrepresented in both fatal and serious injury crashes in Victoria. As an enforcement countermeasure, preliminary oral fluid tests to detect drug driving were introduced in Victoria, Australia in December 2004. Recent research has modelled the relationships between prevalences of THC and methamphetamine in fatally and seriously injured drivers and (a) the annual numbers of random and targeted drug tests during 2010-2016 and (b) the positive detection rates from these tests. The increase in roadside drug tests in Victoria from 42,000 in 2013 (1% of licensed drivers) to 100,000 per year (2.2% of drivers), particularly targeted tests, is estimated to have saved 33 fatal crashes (13.7% reduction) and at least 80 serious injury crashes (1.4% reduction) per year. Based on the findings from this research, further increases in targeted and random roadside drug tests are warranted, up to at least 390,100 total tests per year, which are estimated to save a further 46 fatal crashes and at least a further 134 serious injury crashes per year.
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Chia, A. C. L., M. G. Irwin, P. W. H. Lee, T. H. W. Lee, and S. F. Man. "Comparison of Stress in Anaesthetic Trainees between Hong Kong and Victoria, Australia." Anaesthesia and Intensive Care 36, no. 6 (November 2008): 855–62. http://dx.doi.org/10.1177/0310057x0803600617.
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A postal survey was sent to anaesthetic trainees in Hong Kong and Victoria, Australia to compare work-related stress levels. Demographic data were collected. Anaesthetist-specific stressors, Maslach Burnout Inventory and Global Job Satisfaction scores were used for psychological testing. The response rates from Hong Kong and Melbourne were 64 of 133 (48.1%) and 108 of 196 (55.1%), respectively. Victorian respondents were older with greater family commitments, but more advanced in fulfilling training requirements. Hong Kong respondents, being faced with both the challenge of dual College requirements, exhibited consistently higher indices of stress (P <0.001) and less job satisfaction (P <0.001). Common occupational stressors related to dealing with critically ill patients and medicolegal concerns. Higher stress scores observed in Hong Kong trainees related to service provision and a perceived lack of resources. Despite the complex nature of stress, its antecedents and manifestations, an inverse relationship between emotional exhaustion and job satisfaction was evident in correlation analysis (P <0.001). This survey suggests that stress was present in some trainees in both areas. Hong Kong trainees may benefit from local development to address mental wellbeing as being important to fulfil this highly competitive training program.
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Kong, F., C. Kyle-Link, J. Hocking, and M. Hellard. "11. SEX AND SPORT: A COMMUNITY BASED PROJECT OF CHLAMYDIA TESTING AND TREATMENT IN RURAL AND REGIONAL VICTORIA." Sexual Health 4, no. 4 (2007): 288. http://dx.doi.org/10.1071/shv4n4ab11.
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Chlamydia is the most common notifiable infectious disease in Australia with the number of notifications increasing 92% over the past 5 years. The "Sex and Sport" Project is piloting a community based chlamydia testing and treatment program reaching young people in a specific community setting, sporting clubs. This multifaceted approach utilises health education, population screening and collection of data on risk taking behaviour as the first steps in enhancing health and shaping future service provisions. The project's primary aim is to assess the feasibility of an outreach testing and treatment program. Secondary aims are to measure the prevalence of chlamydia and assess sexual risk behaviour in this population. Strong community collaborations and integration into local health services through the Primary Care Partnerships is important in the project's sustainability; in particular key community members respected by sporting clubs needed to be identified, capacity developed to deliver effective health promotion messages and improve young people's access to sexual health services. Additionally, local knowledge has guided overall program implementation and provides opportunities for capacity building to regionally based services. For example, poor access to sexual health services is being addressed by the participants being able to access services via telephone consultation with Melbourne Sexual Health Centre. Approximately 1000 Victorians aged 16-25 years from the Loddon Mallee region of Victoria will be tested between June and September 2007. This paper will report on the feasibility, challenges and possible solutions in establishing a community based outreach testing and treatment program.
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Wong, Nicole X., Nigel W. Crawford, Jane Oliver, Alissa McMinn, Natasha S. Ching, Ciara Baker, Pierre R. Smeesters, Andrew J. Daley, and Andrew C. Steer. "A Cluster of Pediatric Invasive Group A Streptococcus Disease in Melbourne, Australia, Coinciding with a High-Burden Influenza Season." Journal of Pediatric Infectious Diseases 14, no. 04 (March 7, 2019): 213–18. http://dx.doi.org/10.1055/s-0038-1677456.
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Background Invasive group A streptococcal disease (IGAS) carries significant morbidity and mortality in children. Fluctuations in disease incidence are well documented. However, the modulating factors that contribute to these changes remain unclear. Prospective monitoring of IGAS cases in Victoria, Australia, showed an increased number of cases in 2017, coinciding with a peak of influenza illness. Methods Children identified to have IGAS are prospectively monitored in Melbourne through a disease surveillance network. Data on their presentation, investigations, and clinical course are collected. An increased number of cases identified between June 1, 2017, and October 31, 2017, have been retrospectively analyzed. Results We identified 22 cases of pediatric IGAS during the study period. Increased case detection occurred during a period of increased influenza disease. Of 11 children in our cohort who underwent respiratory viral testing, 4 were confirmed to have concurrent respiratory tract illnesses, and 2 were confirmed to have influenza.
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Lim, M. S. C., M. Hellard, C. El-Hayek, M. Cuevas, C. Fairley, D. Leslie, N. Roth, B. Tee, and M. Stoove. "P3.123 Hepatitis C Testing and Incidence in HIV-Positive Men Who Have Sex with Men in Melbourne, Victoria. A Retrospective Cohort Study." Sexually Transmitted Infections 89, Suppl 1 (July 2013): A186.1—A186. http://dx.doi.org/10.1136/sextrans-2013-051184.0582.
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Young, Jesse T., Cheneal Puljević, Alexander D. Love, Emilia K. Janca, Catherine J. Segan, Donita Baird, Rachel Whiffen, Stan Pappos, Emma Bell, and Stuart A. Kinner. "Staying Quit After Release (SQuARe) trial protocol: a randomised controlled trial of a multicomponent intervention to maintain smoking abstinence after release from smoke-free prisons in Victoria, Australia." BMJ Open 9, no. 6 (June 2019): e027307. http://dx.doi.org/10.1136/bmjopen-2018-027307.
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IntroductionSmoke-free policies have been introduced in prisons internationally. However, high rates of relapse to smoking after release from prison indicate that these policies typically result in short-term smoking cessation only. These high rates of relapse, combined with a lack of investment in relapse prevention, highlight a missed opportunity to improve the health of a population who smoke tobacco at two to six times the rate of the general population. This paper describes the rationale and design of a randomised controlled trial, testing the effectiveness of a caseworker-delivered intervention promoting smoking cessation among former smokers released from smoke-free prisons in Victoria, Australia.Methods and analysisThe multicomponent, brief intervention consists of behavioural counselling, provision of nicotine spray and referral to Quitline and primary care to promote use of government-subsidised smoking cessation pharmacotherapy. The intervention is embedded in routine service delivery and is administered at three time points: one prerelease and two postrelease from prison. Control group participants will receive usual care. Smoking abstinence will be assessed at 1 and 3 months postrelease, and confirmed with carbon monoxide breath testing. Linkage of participant records to survey and routinely collected administrative data will provide further information on postrelease use of health services and prescribed medication.Ethics and disseminationEthical approval has been obtained from the Corrections Victoria Research Committee, the Victorian Department of Justice Human Research Ethics Committee, the Department of Human Services External Request Evaluation Committee and the University of Melbourne Human Research Ethics Committee. Results will be submitted to major international health-focused journals. In case of success, findings will assist policymakers to implement urgently needed interventions promoting the maintenance of prison-initiated smoking abstinence after release, to reduce the health disparities experienced by this marginalised population.Trial registration numberACTRN12618000072213; Pre-results.
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Chan, Jun Keat, Kah Hong Yep, Sarah Magarey, Zoe Keon-Cohen, and Matt Acheson. "Fit Testing Disposable P2/N95 Respirators during COVID-19 in Victoria, Australia: Fit Check Evaluation, Failure Rates, and a Survey of Healthcare Workers." COVID 1, no. 1 (July 6, 2021): 83–96. http://dx.doi.org/10.3390/covid1010007.
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Quantitative fit testing was utilised to evaluate the Department of Health and Human Services in Victoria (DHHS) recommended fit check and determine pass/fail rates for self-selected P2/N95 respirators. Survey experience and training related to P2/N95 respirators were also obtained. This was an observational study at a specialist tertiary referral centre, Melbourne, Australia, between 29 May 2020 and 5 June 2020. The primary outcome was quantitative fit test pass/fail results, with fit check reported against fit test as a 2 × 2 contingency table. The secondary outcomes were the number of adjustments needed to pass, as well as the pass rates for available sizes and types of self-selected respirators, survey data for attitudes, experience and training for P2/N95 respirators. The fit check predicts respirator seal poorly (PPV 34.1%, 95% CI 25.0–40.5). In total, 69% (40/58) of respirators failed quantitative fit testing after initial respirator application and is a clinically relevant finding (first-up failure rate for P2/N95 respirators). Only one person failed the fit test for all three respirator fit tests. There was significant variability between each of the seven types of self-selected P2/N95 respirators, although sample sizes were small. Few participants were trained in the use of P2/N95 respirators or the fit check prior to COVID-19, with a high number of participants confident in achieving a P2/95 respirator seal following a fit test. The fit check alone was not a validated method in confirming an adequate seal for P2/N95 respirators. Quantitative fit testing can facilitate education, improve the seal of P2/N95 respirators, and needs to be integrated into a comprehensive Respiratory Protection Program (RPP).
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Zablotska, I., G. Prestage, A. Grulich, J. Imrie, and S. Kippax. "27. CAN UNPROTECTED ANAL INTERCOURSE WITH REGULAR AND CASUAL PARTNERS EXPLAIN THE DIVERGING TRENDS IN HIV EPIDEMIC IN AUSTRALIA?" Sexual Health 4, no. 4 (2007): 295. http://dx.doi.org/10.1071/shv4n4ab27.
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Introduction: Worldwide, increases in unprotected anal intercourse have been linked to the resurgence in HIV and STI in gay men. We assessed whether changes in UAI within regular and casual relationships may explain the diverging trends in HIV in three Australian states - NSW, Victoria and Queensland. Methods: We used the data from the annual cross-sectional Gay Community Periodic Surveys conducted annually in Sydney since 1996 and in Melbourne and Queensland since 1998. A short self-administered questionnaire asks about HIV serostatus, sexual health testing and behaviours relevant to HIV epidemic. We present time trends in seroconcordance and unprotected sex with regular and casual partners. Results: Currently, about one third of gay men report being in monogamous regular relationships, and this proportion has been slowly increasing everywhere. The self-reported UAI with regular partners (UAIR) was highest among men in seroconcordant positive relationships, lower among seroconcordant negative partners and lowest in non seroconcordant relationships. From 1998 to 2006, the rates of UAIR consistently increased by 10% in all three states and in all relationships by serostatus. The rates of UAI with casual partners (UAIC) were historically highest in NSW. From a peak in 2001, UAIC rates have consistently declined in NSW, but continuing increases were observed in Victoria and Queensland. Higher rates of nondisclosure of HIV were also observed in the context of UAIC in the latter two states. Conclusion: Changes in unprotected sex with casual partners may be responsible for the slowing of HIV epidemic in NSW. Sustained investment in policies and programs are important in achieving behaviour change.
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Chow, Eric PF, Deborah A. Williamson, Ria Fortune, Catriona S. Bradshaw, Marcus Y. Chen, Glenda Fehler, Vesna De Petra, Benjamin P. Howden, and Christopher K. Fairley. "Prevalence of genital and oropharyngeal chlamydia and gonorrhoea among female sex workers in Melbourne, Australia, 2015–2017: need for oropharyngeal testing." Sexually Transmitted Infections 95, no. 6 (May 21, 2019): 398–401. http://dx.doi.org/10.1136/sextrans-2018-053957.
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ObjectiveThe Victorian legislation requires sex workers to have quarterly screening for genital chlamydia and gonorrhoea, but screening for oropharyngeal infection is not mandatory in Victoria, Australia. In 2017, oropharyngeal screening for gonorrhoea and chlamydia was added as part of the routine quarterly screening for sex workers attending the Melbourne Sexual Health Centre (MSHC). The aim of this study was to examine the prevalence of oropharyngeal gonorrhoea and chlamydia among female sex workers (FSW).MethodsWe included females who (1) self-identified as sex workers or were attended MSHC for a sex work certificate and (2) had tested for any STI or HIV, between March 2015 and December 2017. The prevalence of HIV, syphilis, chlamydia and gonorrhoea was calculated.ResultsThere were 8538 FSW consultations among 2780 individuals during the study period. There was a twofold increase in genital gonorrhoea (from 0.5% (95% CI 0.3% to 0.9%) to 1.1% (95% CI 0.8% to 1.5%); ptrend=0.047) and a 1.5-fold increase in genital chlamydia (from 2.2% (95% CI 1.6% to 2.8%) to 3.2% (95% CI 2.6% to 3.8%); ptrend=0.031) during the period. Overall, the prevalence of HIV (0.2% (95% CI 0.1% to 0.3%)) and syphilis (0.1% (95% CI 0.0% to 0.2%)) remained low and did not change over time. In 2017, the prevalence of oropharyngeal gonorrhoea was 2.0% (95% CI 1.6% to 2.6%) and oropharyngeal chlamydia was 2.1% (95% CI 1.6% to 2.7%). Among FSW who were tested positive for gonorrhoea and chlamydia, 55% (n=41) and 34% (n=45) only tested positive in the oropharynx but not genital for gonorrhoea and chlamydia, respectively.ConclusionThe prevalence of oropharyngeal gonorrhoea and chlamydia is similar to the prevalence at genital sites and is often independent of genital infection. It is important to test the oropharynx and genital site for chlamydia and gonorrhoea among FSW.
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Vodstrcil, Lenka A., Christopher K. Fairley, Deborah A. Williamson, Catriona S. Bradshaw, Marcus Y. Chen, and Eric P. F. Chow. "Immunity to hepatitis A among men who have sex with men attending a large sexual health clinic in Melbourne, Australia, 2012–2018." Sexually Transmitted Infections 96, no. 4 (March 13, 2020): 265–70. http://dx.doi.org/10.1136/sextrans-2019-054327.
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BackgroundOutbreaks of hepatitis A are being reported more commonly among men who have sex with men (MSM) globally. Australia has also reported a sharp increase in the number of cases of hepatitis A in 2017. This study aimed to determine the level of immunity to hepatitis A among MSM attending a large urban sexual health clinic in Victoria in the lead up to recent outbreak.MethodsThis was a retrospective audit of serological testing data from first-time MSM attendees at Melbourne Sexual Health Centre (MSHC) in Australia from 1 January 2012 to 31 December 2018. We determined the proportion of MSM who were tested and who had serological detection of hepatitis A IgG, stratified by age and calendar year. We used univariable and multivariable logistic regression to investigate factors associated with testing for and detection of hepatitis A IgG.ResultsThere were 16 609 first-time MSM attendees at MSHC over the 7-year period, of which 9718 (59%, 95% CI 58% to 60%) were tested for hepatitis A IgG. There was a 2% annual increase in the proportion of men tested (from 60% in 2012 to 69% in 2018; OR=1.02, 95% CI 1.00 to 1.03, p=0.025). Men born outside of Australia/New Zealand, and younger men <30 years had higher odds of being tested. Of those tested, 44% (n=4304, 95% CI 43% to 45%) had hepatitis A IgG detected at their first visit, with no change over time (OR=1.01, 95% CI 0.99 to 1.03, p=0.210). Detection of hepatitis A IgG was associated with being aged 30 years or older (adjusted OR=2.06, 95% CI 1.89 to 2.24, p<0.001) or being born overseas versus Australia/New Zealand (AOR=1.21, 95% CI 1.11 to 1.31, p<0.001).ConclusionHepatitis A immunity among MSM remains below the estimated 70% required to prevent outbreaks. Measures including increased testing and higher vaccination coverage are needed to prevent outbreaks and to limit the number of cases and deaths.
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Griggs, Joanne. "Single-Case Study of Appetite Control in Prader-Willi Syndrome, Over 12-Years by the Indian Extract Caralluma fimbriata." Genes 10, no. 6 (June 12, 2019): 447. http://dx.doi.org/10.3390/genes10060447.
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This paper reports on the successful management of hyperphagia (exaggerated hunger) in a 14yr-old female with Prader–Willi syndrome (PWS). This child was diagnosed with PWS, (maternal uniparental disomy) at 18 months due to developmental delay, hypertonia, weight gain and extreme eating behaviour. Treatment of a supplement for appetite suppression commenced at 2 years of age. This single-case records ingestion of an Indian cactus succulent Caralluma fimbriata extract (CFE) over 12 years, resulting in anecdotal satiety, free access to food and management of weight within normal range. CFE was administered in a drink daily and dose was slowly escalated by observation for appetite suppression. Rigorous testing determined blood count, vitamins, key minerals, HbA1c, IGF-1 and function of the liver and thyroid all within normal range. The report suggests a strategy for early intervention against hyperphagia and obesity in PWS. This case was the instigator of the successful Australian PWS/CFE pilot and though anecdotal, the adolescent continues to ingest CFE followed by paediatricians at the Royal Children’s Hospital Melbourne, Victoria, Australia. Future clinical trials are worth considering, to determine an appropriate dose for individuals with PWS.
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McDonald, A., and J. M. Kaldor. "37. MONITORING HIV TRANSMISSION AMONG MEN SEEN AT METROPOLITAN SEXUAL HEALTH CLINICS IN AUSTRALIA, 1996-2005." Sexual Health 4, no. 4 (2007): 299. http://dx.doi.org/10.1071/shv4n4ab37.
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National surveillance for newly diagnosed HIV infection indicates an increasing trend in Queensland, South Australia and Victoria but not in New South Wales. It was not clear if trends in newly diagnosed HIV infection were due to different patterns of HIV antibody testing. We report the pattern of HIV antibody testing among people seen through a network of sexual health clinics in Australia. Six public metropolitan sexual health clinics (Sydney Sexual Health Centre (SSHC), South West Sexual Health Centre (SSWSHC), NSW; Brisbane Sexual Health Clinic (BSHC), Gold Coast Sexual Health Clinic (GCSHC), QLD; Clinic 275, SA; Melbourne Sexual Health Centre (MSHC), VIC) provide annual tabulations of the number of people seen, the number tested for HIV antibody, and the number with newly diagnosed HIV infection, broken down by sex, exposure category and testing history. The number of men seen at the clinics ranged from 17 138 in 1996 to 19 184 in 2005. Among men seen, the percentage who were tested for HIV declined from 62% in 1996 to 50% in 2001 and increased to 56% in 2005. HIV prevalence remained stable in 1996-2005 at 0.5% and was highest at SSHC (0.7-1.1%) and among homosexually active men (1.8% in 1996 and 1.6% in 2005). The percentage of men retested within 12 months of a negative test increased from 41% in 1996 to 44% in 2005. At SSHC, retesting among homosexually active men declined from 56% in 1996 to 44% in 2001 and increased to 58% by 2005. At Clinic 275 and MSHC, 50-60% and around 50% of homosexually active men were retested in 1996 - 2005 and in 2004-2005, respectively. HIV infection was newly diagnosed in 0.4% (8) in 1996 and in 0.8% (26) in 2005. While HIV antibody testing patterns vary between the clinics, incidence of newly diagnosed HIV infection has remained low.
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Carlton, Caroline, Jacqueline M. Norris, Evelyn Hall, Michael P. Ward, Stephanie Blank, Shelby Gilmore, Anjuli Dabydeen, Vivian Tran, and Mark E. Westman. "Clinicopathological and Epidemiological Findings in Pet Cats Naturally Infected with Feline Immunodeficiency Virus (FIV) in Australia." Viruses 14, no. 10 (September 30, 2022): 2177. http://dx.doi.org/10.3390/v14102177.
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Feline immunodeficiency virus (FIV) infection in experimentally infected domestic cats produces characteristic clinical manifestations including hematological changes, neurological disease, neoplasia (most notably lymphoma) and lymphopenia-mediated immunodeficiency predisposing cats to a range of secondary infections. Conflicting reports exist, however, with regard to disease associations and survival time in naturally FIV-infected cats. The purpose of this retrospective case–control study was to investigate the effect of natural FIV infection on hematological, blood biochemical and urinalysis parameters and survival time in three cohorts of pet cats in Australia. Cohorts 1 and 2 were recruited from a large veterinary hospital in Melbourne, Victoria (n = 525 and 282), while a third cohort consisted of cats recruited from around Australia as part of a FIV field vaccine efficacy trial (n = 425). FIV-infected cats in cohorts 1, 2 and 3 were found to have 15/37 (41%), 13/39 (33%) and 2/13 (15%) clinicopathological parameters significantly different to FIV-uninfected cats, respectively. Two changes in FIV-infected cats in cohort 1, hypochromia (low hemoglobin) and hyperglobulinemia, were outside the supplied reference intervals and should serve as diagnostic triggers for FIV testing. Kaplan–Meier survival analysis of cats in cohorts 1 and 2 combined did not find any difference between FIV-infected and FIV-uninfected cats, however a confounding factor was a large euthanasia rate within the first 12 months in both groups. Three significant (p < 0.05) spatial clusters of FIV infection were identified in Melbourne. A possible relationship between FIV infection status and socioeconomic disadvantage was discovered, based on three government indices of socioeconomic status (p < 0.001). Until longitudinal field studies are performed in Australia to further investigate the long-term effects of natural FIV infection, Australian veterinarians should consider FIV to be an important infection of pet cats, and recommend measures to prevent FIV infection.
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Berridge, Bonita J., Terence V. McCann, Ali Cheetham, and Dan I. Lubman. "Perceived Barriers and Enablers of Help-Seeking for Substance Use Problems During Adolescence." Health Promotion Practice 19, no. 1 (February 1, 2017): 86–93. http://dx.doi.org/10.1177/1524839917691944.
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Aim. Receiving professional help early can reduce long-term harms associated with substance use. However, little is known about the factors that influence help-seeking for substance use problems during early-mid adolescence, prior to the emergence of disorder. Given that beliefs regarding help-seeking are likely to develop early, understanding adolescent views of help-seeking during this period is likely to provide important information for prevention and intervention efforts. The current study identifies perceptions that would facilitate or prevent adolescents from seeking support for substance use problems from formal and informal help sources. Method. Thirty-four 12- to 16-year-olds from two schools in Melbourne, Victoria, Australia, were recruited. A qualitative interpretative design was used, incorporating semistructured, audio-recorded interviews. Results. Three overlapping themes that reflected barriers or enablers to help-seeking were identified: approachability, confidentiality and trustworthiness, and expertise. Help-seeking was facilitated when adolescents believed that the help source would be supportive and understanding, would keep information confidential, and had expertise in the alcohol and drug field. Conversely, adolescents were reluctant to seek help from sources they believed would be judgmental, lacked expertise, or would inform their parents. Conclusions. These findings highlight perceptions that may influence help-seeking for alcohol and drug problems during adolescence. Further research is needed to determine if help-seeking can be facilitated by improving parents’ and peers’ knowledge and promoting health professionals’ expertise in working with young people’s alcohol and drug issues.
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Goller, Jane L., Rebecca J. Guy, Judy Gold, Megan S. C. Lim, Carol El-Hayek, Mark A. Stoove, Isabel Bergeri, et al. "Establishing a linked sentinel surveillance system for blood-borne viruses and sexually transmissible infections: methods, system attributes and early findings." Sexual Health 7, no. 4 (2010): 425. http://dx.doi.org/10.1071/sh09116.
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Objective: To describe the attributes and key findings from implementation of a new blood-borne virus (BBV) and sexually transmissible infection (STI) sentinel surveillance system based on routine testing at clinical sites in Victoria, Australia. Methods: The Victorian Primary Care Network for Sentinel Surveillance (VPCNSS) on BBV and STI was established in 2006 at 17 sites. Target populations included men who have sex with men (MSM), young people and injecting drug users (IDU). Sites collected demographic and risk behaviour information electronically or using paper surveys from patients undergoing routine HIV or STI (syphilis, chlamydia (Chlamydia trachomatis)) or hepatitis C virus (HCV) testing. These data were linked with laboratory results. Results: Between April 2006 and June 2008, data were received for 67 466 tests and 52 042 questionnaires. In clinics providing electronic data, >90% of individuals tested for HIV, syphilis and chlamydia had risk behaviour information collected. In other clinics, survey response rates were >85% (HIV), 43.5% (syphilis), 42.7–66.5% (chlamydia) and <20% (HCV). Data completeness was >85% for most core variables. Over time, HIV, syphilis and chlamydia testing increased in MSM, and chlamydia testing declined in females (P = 0.05). The proportion of positive tests among MSM was 1.9% for HIV and 2.1% for syphilis. Among 16–24-year-olds, the proportion positive for chlamydia was 10.7% in males and 6.9% in females. Among IDU, 19.4% of HCV tests were antibody positive. Conclusions: The VPCNSS has collected a large, rich dataset through which testing, risk behaviours and the proportion positive can be monitored in high-risk groups, offering a more comprehensive BBV and STI surveillance system for Victoria. Building system sustainability requires an ongoing focus.
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Scull, Janet, Jane Page, Megan L. Cock, Cuc Nguyen, Lisa Murray, Patricia Eadie, and Joseph Sparling. "Developing and Validating a Tool to Assess Young Children’s Early Literacy Engagement." Australasian Journal of Early Childhood 46, no. 2 (May 3, 2021): 179–95. http://dx.doi.org/10.1177/18369391211009696.
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There is growing recognition that literacy learning takes place in the years prior to formal schooling and that young children develop literacy-like behaviours through exposure to interactions in shared contexts in which literacy is a component. Despite this, there are few assessments that measure the very early literacy skills that children develop before 36 months of age. This article reports on the design and validation of a new instrument – the Early Literacy Engagement Assessment (ELEA). This tool was developed to provide insights into the impact of Conversational Reading, a key pedagogical strategy implemented at Families as First Teachers playgroups, on young children’s early receptive and expressive vocabulary and literacy skills. The instrument was trialled with 104 children living in locations across Melbourne, Victoria, and 39 Aboriginal children living in remote communities in the Northern Territory. The trial process was undertaken in two phases: (1) a technical assessment to test item consistency, characteristics and placement and (2) concurrent validity testing against items from the Clinical Evaluation of Language Fundamentals Preschool-2 tool. The findings from the trial and validation process indicate that overall the ELEA discriminates well between children of high and low ability, and it is a useful tool in the authentic assessment of expressive and receptive vocabulary skills in young children.
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Seiler, Natalie, Matthew Ng, Midya Dawud, Subhash Das, Shu-Haur Ooi, and Astrid Waterdrinker. "Demographic and clinical factors associated with psychiatric inpatient admissions during the COVID-19 pandemic." Australasian Psychiatry 30, no. 2 (December 6, 2021): 229–34. http://dx.doi.org/10.1177/10398562211052903.
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Objective: The COVID-19 pandemic may cause a major mental health impact. We aimed to identify demographic or clinical factors associated with psychiatric admissions where COVID-19 was attributed to contribute to mental state, compared to admissions which did not. Methods: A retrospective cohort study was undertaken of inpatients admitted to Northern Psychiatric Unit 1, Northern Hospital in Melbourne, Victoria, Australia during 27/02/2020 to 08/07/2020. Data were extracted for participants who identified COVID-19 as a stressor compared to participants who did not. Fisher’s exact test and Mann-Whitley rank sum test were used. Results: Thirty six of 242 inpatients reported the COVID-19 pandemic contributed to mental ill health and subsequent admission. Reasons given included social isolation, generalized distress about the pandemic, barriers to support services, disruption to daily routine, impact on employment, media coverage, re-traumatization, cancelled ECT sessions, loss of loved ones, and increased drug use during the lockdown. Chronic medical conditions or psychiatric multimorbidity were positively associated and smoking status was negatively associated with reporting the COVID-19 pandemic as a contributor to mental ill health. Conclusion: Screening and identifying vulnerable populations during and after the global disaster is vital for timely and appropriate interventions to reduce the impact of the pandemic worldwide.
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Carnell, George W., Claudia M. Trombetta, Francesca Ferrara, Emanuele Montomoli, and Nigel J. Temperton. "Correlation of Influenza B Haemagglutination Inhibiton, Single-Radial Haemolysis and Pseudotype-Based Microneutralisation Assays for Immunogenicity Testing of Seasonal Vaccines." Vaccines 9, no. 2 (January 28, 2021): 100. http://dx.doi.org/10.3390/vaccines9020100.
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Influenza B is responsible for a significant proportion of the global morbidity, mortality and economic loss caused by influenza-related disease. Two antigenically distinct lineages co-circulate worldwide, often resulting in mismatches in vaccine coverage when vaccine predictions fail. There are currently operational issues with gold standard serological assays for influenza B, such as lack of sensitivity and requirement for specific antigen treatment. This study encompasses the gold standard assays with the more recent Pseudotype-based Microneutralisation assay in order to study comparative serological outcomes. Haemagglutination Inhibition, Single Radial Haemolysis and Pseudotype-based Microneutralisation correlated strongly for strains in the Yamagata lineage; however, it correlated with neither gold standard assays for the Victoria lineage.
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Burrell, Sam, Lenka A. Vodstrcil, Christopher K. Fairley, Alex Kilner, Catriona S. Bradshaw, Marcus Y. Chen, and Eric P. F. Chow. "Hepatitis A vaccine uptake among men who have sex with men from a time-limited vaccination programme in Melbourne in 2018." Sexually Transmitted Infections 96, no. 2 (July 25, 2019): 110–14. http://dx.doi.org/10.1136/sextrans-2019-054132.
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ObjectivesIn 2017, an outbreak of hepatitis A among gay, bisexual and other men who have sex with men (MSM) was reported in Victoria, Australia. In 2018, the Victorian government implemented a free hepatitis A vaccination programme targeting all Victorian MSM. This study aimed to determine hepatitis A vaccine uptake among MSM in a sexual health clinic in Melbourne.MethodsAll MSM attending the Melbourne Sexual Health Centre (MSHC) in 2018 were included. Chart review was performed to determine the proportion of men vaccinated for at least one dose of hepatitis A and to examine why men did not receive the vaccine. Multivariable logistic regression was performed to examine the factors associated with vaccine uptake. Vaccine uptake was defined as receipt of at least one dose of hepatitis A vaccine.ResultsOf the 9582 MSM who attended MSHC in 2018, 61.3% (95% CI 60.3% to 62.2%) self-reported already being immune to hepatitis A. Of the 3713 remaining eligible men, 62.7% (95% CI 61.1% to 64.2%) received at least one dose of the hepatitis A vaccine on the day of attendance. Compared with MSM not living with HIV and not taking pre-exposure prophylaxis (PrEP), MSM taking PrEP (adjusted OR 1.28; 95% CI 1.01 to 1.62) were more likely to receive the vaccine. 1386 men (37.3%) did not receive the vaccine and 55.4% were not offered the vaccine by their treating clinician. 300 men (21.6%) were identified as non-immune after serological testing but did not return for vaccination. By the end of 2018, 85.5% of MSHC attendees (8196/9582) were immune to hepatitis A.ConclusionThe critical vaccination threshold for hepatitis A has been estimated at >70%. Continuation of the targeted hepatitis A vaccination programme will improve immunity among the MSM population to prevent ongoing transmission and the likelihood of future outbreaks.
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MacLean, Sarah. "Out-of-Home Care As an Institutional Risk Environment for Volatile Substance Use." Children Australia 37, no. 1 (March 2012): 23–30. http://dx.doi.org/10.1017/cha.2012.4.
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The exploratory study of meanings of volatile substance use (VSU) on which this article draws (involving 28 young people living in Melbourne, Victoria, Australa, aged from 13 to 24 years, each with experience of VSU, and 14 expert workers) was not designed to investigate any relationship between VSU and living in out-of-home care while subject to protective orders. However, when asked about their lives at the time they commenced or intensified VSU, 8 participants were adamant that living in out-of-home care was a significant factor. Two narratives reiterated by these young people are identified in the article: first that VSU is part of life in out-of-home care, and second that VSU ceases to be appropriate after leaving care. Young people who are living in out-of-home care report substantially higher levels of VSU than occur across the general population. This article shows how narrative accounts (even when expressed by small numbers of participants) provide insight into how VSU and other drug use may become embedded in particular institutional settings through assuming meanings and utility for users that are specific to these environments. While previous literature on the aetiology of VSU generally emphasises individual or familial risk factors, this article argues that out-of-home care may function, at least in some instances, as an institutional ‘risk environment’ for VSU and that this should be further explored through future research. Adjusting models of care may offer new strategies for responding to this form of drug use.
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Constantinou, Heidi, Christopher K. Fairley, Jane S. Hocking, Catriona S. Bradshaw, Edmond P. H. Choi, Kate Maddaford, Tiffany R. Phillips, and Eric P. F. Chow. "Associations Between Methods of Meeting Sexual Partners and Sexual Practices Among Heterosexuals: Cross-sectional Study in Melbourne, Australia." JMIR Formative Research 5, no. 7 (July 20, 2021): e26202. http://dx.doi.org/10.2196/26202.
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Background The association between meeting partners on the web and sexual practices has been understudied in heterosexuals. Objective This study aims to examine the associations between the methods of meeting partners and sexual practices and HIV and sexually transmitted infections (STIs) in heterosexuals. Methods We conducted a survey among heterosexuals attending the Melbourne Sexual Health Centre in 2019. This survey asked about the methods through which the participants engaged in meeting their sexual partners, sexual practices, and intravenous drug use (IVDU) over the past 3 months. The participants’ HIV and STI (chlamydia, gonorrhea, and syphilis) status was obtained from clinical testing. Multivariable logistic regression was used to examine the association between each method of meeting and the participants’ sexual practices, IVDU, and STI status. Results A total of 698 participants (325 men and 373 women) were included in the study. Most of the participants reported using only one method to meet partners (222/325, 68.3% men; 245/373, 65.7% women; P=.05). The men met partners most commonly at social venues (eg, bar, pub, or party; 126/325, 38.8%), whereas the women met partners most commonly through friends or family (178/373, 47.7%). Paying for sex was associated with men meeting partners at sex venues (adjusted odds ratio [AOR] 145.34, 95% CI 26.13-808.51) and on the internet (AOR 10.00, 95% CI 3.61-27.55). There was no association between IVDU and methods of meeting. Social venues were associated with condomless vaginal sex among men (AOR 3.31, 95% CI 1.94-5.71) and women (AOR 2.58, 95% CI 1.61-4.13) and testing positive for STI among men (AOR 3.04, 95% CI 1.24-7.48) and women (AOR 3.75, 95% CI 1.58-8.89). Conclusions Heterosexuals who met partners at social venues had a more than threefold risk of testing positive for STIs, indicating that heterosexuals may benefit from health promotion campaigns that are delivered through a public setting.
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Zhang, Alexis Ceecee, and Laura E. Downie. "Preliminary Validation of a Food Frequency Questionnaire to Assess Long-Chain Omega-3 Fatty Acid Intake in Eye Care Practice." Nutrients 11, no. 4 (April 11, 2019): 817. http://dx.doi.org/10.3390/nu11040817.
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Clinical recommendations relating to dietary omega-3 essential fatty acids (EFAs) should consider an individual’s baseline intake. The time, cost, and practicality constraints of current techniques for quantifying omega-3 levels limit the feasibility of applying these methods in some settings, such as eye care practice. This preliminary validation study, involving 40 adults, sought to assess the validity of a novel questionnaire, the Clinical Omega-3 Dietary Survey (CODS), for rapidly assessing long-chain omega-3 intake. Estimated dietary intakes of long-chain omega-3s from CODS correlated with the validated Dietary Questionnaire for Epidemiology Studies (DQES), Version 3.2, (Cancer Council Victoria, Melbourne, Australia) and quantitative assays from dried blood spot (DBS) testing. The ‘method of triads’ model was used to estimate a validity coefficient (ρ) for the relationship between the CODS and an estimated “true” intake of long-chain omega-3 EFAs. The CODS had high validity for estimating the ρ (95% Confidence Interval [CI]) for total long-chain omega-3 EFAs 0.77 (0.31–0.98), docosahexaenoic acid 0.86 (0.54–0.99) and docosapentaenoic acid 0.72 (0.14–0.97), and it had moderate validity for estimating eicosapentaenoic acid 0.57 (0.21–0.93). The total long-chain omega-3 EFAs estimated using the CODS correlated with the Omega-3 index (r = 0.37, p = 0.018) quantified using the DBS biomarker. The CODS is a novel tool that can be administered rapidly and easily, to estimate long-chain omega-3 sufficiency in clinical settings.
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Barlow, John W., Andrea J. Curtis, Lorna E. Raggatt, Nicole M. Loidl, Duncan J. Topliss, and Jan R. Stockigt. "Drug competition for intracellular triiodothyronine-binding sites." European Journal of Endocrinology 130, no. 4 (April 1994): 417–21. http://dx.doi.org/10.1530/eje.0.1300417.
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Barlow JW, Curtis AJ, Raggatt LE, Loidl NM, Topliss DJ. Stockigt JR. Drug competition for intracellular triiodothyronine-binding sites. Eur J Endocrinol 1944;130:417–21. ISSN 0804–4643 A variety of substances, including frusemide, non-esterified fatty acids (NEFAs) and non-steroidal antiinflammatory drugs (NSAIDs), can compete for triiodothyronine (T3)-binding sites in serum and at the cell surface. We examined the competitive potency of these agents at intracellular T3-binding sites in order to assess their potential to act as T3 antagonists. Competition for [125I]T3 binding was determined using hydroxyapatite separation in cytosols and nuclear extracts prepared from livers of Macaca fascicularis. The T3 affinities were 15.8 ± 1.2 nmol/l in cytosol and 0.23 ± 0.02 nmol/l in nuclear extract. Does–response curves were analysed by a four-parameter sigmoid curve-fitting program to determine competitor potency. The nineteen agents tested included various NSAIDs, NEFAs, non-bile acid cholephils (NBACs), frusemide, amiodarone and the flavonoid EMD 21388. In nuclear extract the most active competitors were linoleic acid (8.5 μmol/l) and linolenic acid (7.8 μmol/l), Potencies of NSAIDs varied between 66 μmol/l (meclofenamic acid) and 525 μmol/l (diclofenac). In cytosol, NEFAs were less potent but NSAIDs were stronger competitors than in nuclear extract. Half-inhibitory potencies in cytosol were between 13.2 μmol/l (meclofenamic acid) and 63.1 μmol/l (flufenamic acid). The NBAC bromosulphthalein was one of the most potent inhibitors in both cytosol and nuclear extract. When expressed relative to T3, diclofenac was a more effective competitor in cytosol than it was in nuclear extract. Amiodarone and EMD 21388 were without effect both in cytosol and nuclear extract. Frusemide (759 μmol/l) was weakly active in cytosol only. The action of T3 was assessed by measuring secretion of sex hormone-binding globulin (SHBG) in Hep-G2 cells. After 3 days with total T3 (0.1 μmol/l), SHBG was 155 ± 15% of the control. Amiodarone (100 μmol/l) and meclofenamic acid (100 μmol/l) were cytotoxic. Bromosulphthalein (10 μmol/l), one of the most potent competitors at both the cytoplasmic and the nuclear level, did not influence the T3-induced rise in SHBG secretion. None of the drugs tested affected the magnitude of maximal induction of SHBG by T3. Substances that compete for serum and cell surface T3-binding sites are also weak competitors for intracellular T3-binding proteins, although the heirarchy of potency differs. Frusemide and diclofenac, with a greater relative potency for cytosolic binding than nuclear binding, may have potential use in investigating the function of cytosolic T3-binding. Amiodarone shows no binding activity and is not a hormone antagonist in primate hepatic tissue. John W Barlow, Ewen Downie Metabolic Unit, Alfred Hospital, Commercial Road, Melbourne, Victoria 3181, Australia
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Jenkinson, Rebecca, Anna Bowring, Paul Dietze, Margaret Hellard, and Megan S. C. Lim. "Young Risk Takers: Alcohol, Illicit Drugs, and Sexual Practices among a Sample of Music Festival Attendees." Journal of Sexually Transmitted Diseases 2014 (December 14, 2014): 1–6. http://dx.doi.org/10.1155/2014/357239.
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Background. Alcohol and other drug use and sexual risk behaviour are increasing among young Australians, with associated preventable health outcomes such as sexually transmissible infections (STIs) on the rise. Methods. A cross-sectional study of young people’s health behaviours conducted at a music festival in Melbourne, Australia, in 2011. Results. 1365 young people aged 16–29 completed the survey; 62% were female with a mean age of 20 years. The majority (94%, n=1287) reported drinking alcohol during the previous 12 months; among those, 32% reported “binge” drinking (6+ drinks) at least weekly. Half (52%) reported ever using illicit drugs and 25% reported past month use. One-quarter (27%) were identified as being at risk of STIs through unprotected sex with new or casual partners during the previous 12 months. Multivariable analyses found that risky sexual behaviour was associated with younger age (≤19 years), younger age of sexual debut (≤15 years), having discussed sexual health/contraception with a doctor, regular binge drinking, and recent illicit drug use. Conclusion. Substance use correlated strongly with risky sexual behaviour. Further research should explore young people’s knowledge of alcohol/drug-related impairment and associated risk-taking behaviours, and campaigns should encourage appropriate STI testing among music festival attendees.
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Prokopyeva, Elena, Olga Kurskaya, Ivan Sobolev, Mariia Solomatina, Tatyana Murashkina, Anastasia Suvorova, Alexander Alekseev, et al. "Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model." Viruses 12, no. 4 (April 21, 2020): 470. http://dx.doi.org/10.3390/v12040470.
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Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. Since preclinical trials of anti-influenza drugs are mainly conducted in mice, we developed an appropriate infection model, using an antigenically-relevant IBV strain, for furtherance of anti-influenza drug testing and influenza vaccine protective efficacy analysis. A Victoria lineage (clade 1A) IBV was serially passaged 17 times in BALB/c mice, and adaptive amino acid substitutions were found in hemagglutinin (HA) (T214I) and neuraminidase (NA) (D432N). By electron microscopy, spherical and elliptical IBV forms were noted. Light microscopy showed that mouse-adapted IBVs caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load, and histopathological features of mouse-adapted IBVs and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of an investigational anti-influenza drug (oseltamivir ethoxysuccinate) and an influenza vaccine (Ultrix®, SPBNIIVS, Saint Petersburg, Russia) showed effectiveness against the mouse-adapted influenza B virus.
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Anderson, Fern, G. Michael Downing, Jan Hill, Lynn Casorso, and Noreen Lerch. "Palliative Performance Scale (PPS): A New Tool." Journal of Palliative Care 12, no. 1 (March 1996): 5–11. http://dx.doi.org/10.1177/082585979601200102.
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The Palliative Performance Scale (PPS), a modification of the Karnofsky Performance Scale, is presented as a new tool for measurement of physical status in palliative care. Its initial uses in Victoria include communication, analysis of home nursing care workload, profiling admissions and discharges to the hospice unit, and, possibly, prognostication. We assessed 119 patients at home, of whom 87 (73%) had a PPS rating between 40% and 70%. Of 213 patients admitted to the hospice unit, 175 (83%) were PPS 20%-50% on admission. The average period until death for 129 patients who died on the unit was 1.88 days at 10% PPS upon admission, 2.62 days at 20%, 6.70 days at 30%, 10.30 days at 40%, 13.87 days at 50%. Only two patients at 60% or higher died in the unit. The PPS may become a basis for comparing drug costs at home and for studying the effects of treatments (e.g. hypodermoclysis) at various levels of physical performance. Validity and reliability testing are currently being undertaken.
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Goller, Jane L., Jacqueline Coombe, Meredith Temple-Smith, Helen Bittleston, Lena Sanci, Rebecca Guy, Christopher Fairley, et al. "Management of Chlamydia Cases in Australia (MoCCA): protocol for a non-randomised implementation and feasibility trial." BMJ Open 12, no. 12 (December 2022): e067488. http://dx.doi.org/10.1136/bmjopen-2022-067488.
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IntroductionThe sexually transmitted infection chlamydia can cause significant complications, particularly among people with female reproductive organs. Optimal management includes timely and appropriate treatment, notifying and treating sexual partners, timely retesting for reinfection and detecting complications including pelvic inflammatory disease (PID). In Australia, mainstream primary care (general practice) is where most chlamydia infections are diagnosed, making it a key setting for optimising chlamydia management. High reinfection and low retesting rates suggest partner notification and retesting are not uniformly provided. The Management of Chlamydia Cases in Australia (MoCCA) study seeks to address gaps in chlamydia management in Australian general practice through implementing interventions shown to improve chlamydia management in specialist services. MoCCA will focus on improving retesting, partner management (including patient-delivered partner therapy) and PID diagnosis.Methods and analysisMoCCA is a non-randomised implementation and feasibility trial aiming to determine how best to implement interventions to support general practice in delivering best practice chlamydia management. Our method is guided by the Consolidated Framework for Implementation Research and the Normalisation Process Theory. MoCCA interventions include a website, flow charts, fact sheets, mailed specimen kits and autofills to streamline chlamydia consultation documentation. We aim to recruit 20 general practices across three Australian states (Victoria, New South Wales, Queensland) through which we will implement the interventions over 12–18 months. Mixed methods involving qualitative and quantitative data collection and analyses (observation, interviews, surveys) from staff and patients will be undertaken to explore our intervention implementation, acceptability and uptake. Deidentified general practice and laboratory data will be used to measure pre-post chlamydia testing, retesting, reinfection and PID rates, and to estimate MoCCA intervention costs. Our findings will guide scale-up plans for Australian general practice.Ethics and disseminationEthics approval was obtained from The University of Melbourne Human Research Ethics Committee (Ethics ID: 22665). Findings will be disseminated via conference presentations, peer-reviewed publications and study reports.
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Constantinou, Heidi, Christopher K. Fairley, Catriona S. Bradshaw, Edmond P. H. Choi, Kate Maddaford, Tiffany R. Phillips, and Eric P. F. Chow. "Factors associated with group sex in heterosexual males and females attending a sexual health clinic in Melbourne, Australia: a cross-sectional survey." Sexual Health 19, no. 1 (March 16, 2022): 39–45. http://dx.doi.org/10.1071/sh21224.
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Background There have been limited studies of group sex among heterosexual individuals. This study aimed to explore the factors associated with group sex among heterosexual males and females to improve risk assessment guidelines and inform sexually transmitted infection (STI) screening requirements. Methods A cross-sectional survey was conducted among heterosexual males and females aged ≥16 years attending the Melbourne Sexual Health Centre between March and April 2019. The survey asked about group sex participation, methods used to meet sexual partners, number of casual and/or regular partners, and injection drug use (IDU) in the previous 3 months. HIV and STI (chlamydia, gonorrhoea, syphilis) diagnoses were extracted. A multivariable logistic regression was conducted to identify the factors associated with group sex participation. Results A total of 698 participants (325 males, 373 females) were included and 4.7% (33/698) had participated in group sex in the previous 3 months. The proportion who participated in group sex increased with age (2.1% in 16–24 years, 5.5% in 25–34 years, 7.8% in ≥35 years, ptrend = 0.010). Meeting partners at sex venues (e.g. brothels) was associated with the highest odds of participating in group sex (aOR = 5.74, 95% CI: 1.20–27.44), followed by dating apps (aOR = 2.99, 95% CI: 1.36–6.58), friends/family (aOR = 2.99, 95% CI: 1.34–6.69) and social venues (e.g. bar) (aOR = 2.73, 95% CI: 1.18–6.30). Group sex was strongly associated with STI positivity (aOR = 6.24, 95% CI: 2.41–16.13). There was no association between group sex and sex, casual and/or regular partners, HIV positivity or IDU. Conclusion Heterosexual individuals participating in group sex had a six-fold risk of testing positive for STIs. Including group sex in a sexual history is useful to determine STI risk and inform testing practices. Safe sex messages on group sex that are delivered through multiple methods (e.g. at sex venues, social venues and dating apps simultaneously) would be beneficial.
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Bush, Matiu R., Henrietta Williams, and Christopher K. Fairley. "HIV is rare among low-risk heterosexual men and significant potential savings could occur through phone results." Sexual Health 7, no. 4 (2010): 495. http://dx.doi.org/10.1071/sh09088.
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Background: The legislation in Victoria requires HIV-positive results to be given in person by an accredited health professional. Many sexual health clinics require all men to receive HIV results in person. Our aim was to determine the proportion of low-risk heterosexual men at a sexual health centre who tested HIV-positive. Methods: The electronic data on all HIV tests performed between 2002 and 2008 on heterosexual men at the Melbourne Sexual Health Centre (MSHC) was reviewed. The individual client files of all heterosexual men who tested HIV-positive were reviewed to determine their risks for HIV at the time that the HIV test was ordered. Results: Over the 6 years there were 33 681 HIV tests performed on men, of which 17 958 tests were for heterosexual men. From these heterosexual men, nine tested positive for the first time at MSHC (0.05%, 95% confidence interval (CI): 0.01%, 0.09%). These nine cases included six men who had had sex with a female partner from the following countries: Thailand, Cambodia, China, East Timor, Botswana and South Africa. Two men had injected drugs and one had a HIV-positive female partner. Of the 17 958 test results for heterosexual males, 14 902 (83% 95% CI: 84%, 86%) test results were for men who did not have a history of intravenous drug use or had sexual contact overseas. Of these 14 902 low-risk men, none tested positive (0%, 95% CI: 0, 0.00025). Conclusion: Asking the 83% of heterosexual men who have an extremely low risk of HIV to return in person for their results is expensive for sexual health clinics and inconvenient for clients. We have changed our policy to permit heterosexual men without risk factors to obtain their HIV-negative results by phone.
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Dawson, Samantha L., Jeffrey M. Craig, Gerard Clarke, Mohammadreza Mohebbi, Phillip Dawson, Mimi LK Tang, and Felice N. Jacka. "Targeting the Infant Gut Microbiota Through a Perinatal Educational Dietary Intervention: Protocol for a Randomized Controlled Trial." JMIR Research Protocols 8, no. 10 (October 21, 2019): e14771. http://dx.doi.org/10.2196/14771.
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Background The early life gut microbiota are an important regulator of the biological pathways contributing toward the pathogenesis of noncommunicable disease. It is unclear whether improvements to perinatal diet quality could alter the infant gut microbiota. Objective The aim of this study is to assess the efficacy of a perinatal educational dietary intervention in influencing gut microbiota in mothers and infants 4 weeks after birth. Methods The Healthy Parents, Healthy Kids randomized controlled trial aimed to recruit 90 pregnant women from Melbourne, Victoria, Australia. At week 26 of gestation, women were randomized to receive dietary advice from their doctor (n=45), or additionally receive a dietary intervention (n=45). The intervention included an educational workshop and 2 support calls aiming to align participants’ diets with the Australian Dietary Guidelines and increase intakes of prebiotic and probiotic foods. The educational design focused on active learning and self-assessment. Behavior change techniques were used to support dietary adherence, and the target behavior was eating for the gut microbiota. Exclusion criteria were age under 18 years, diagnosed mental illnesses, obesity, diabetes mellitus, diagnosed bowel conditions, exclusion diets, illicit drug use, antibiotic use, prebiotic or probiotic supplementation, and those lacking dietary autonomy. The primary outcome measure is a between-group difference in alpha diversity in infant stool collected 4 weeks after birth. Secondary outcomes include evaluating the efficacy of the intervention in influencing infant and maternal stool microbial composition and short chain fatty acid concentrations, epigenetic profile, and markers of inflammation and stress, as well as changes in maternal dietary intake and well-being. The study and intervention feasibility and acceptance will also be evaluated as secondary outcomes. Results The study results are yet to be written. The first participant was enrolled on July 28, 2016, and the final follow-up assessment was completed on October 11, 2017. Conclusions Data from this study will provide new insights regarding the ability of interventions targeting the perinatal diet to alter the maternal and infant gut microbiota. If this intervention is proven, our findings will support larger studies aiming to guide the assembly of gut microbiota in early life. Trial Registration Australian Clinical Trials Registration Number ACTRN12616000936426; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370939 International Registered Report Identifier (IRRID) DERR1-10.2196/14771
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Allen-Graham, Judith, Lauren Mitchell, Natalie Heriot, Roksana Armani, David Langton, Michele Levinson, Alan Young, Julian A. Smith, Tom Kotsimbos, and John W. Wilson. "Electronic health records and online medical records: an asset or a liability under current conditions?" Australian Health Review 42, no. 1 (2018): 59. http://dx.doi.org/10.1071/ah16095.
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Objective The aim of the present study was to audit the current use of medical records to determine completeness and concordance with other sources of medical information. Methods Medical records for 40 patients from each of five Melbourne major metropolitan hospitals were randomly selected (n=200). A quantitative audit was performed for detailed patient information and medical record keeping, as well as data collection, storage and utilisation. Using each hospital’s current online clinical database, scanned files and paperwork available for each patient audited, the reviewers sourced as much relevant information as possible within a 30-min time allocation from both the record and the discharge summary. Results Of all medical records audited, 82% contained medical and surgical history, allergy information and patient demographics. All audited discharge summaries lacked at least one of the following: demographics, medication allergies, medical and surgical history, medications and adverse drug event information. Only 49% of records audited showed evidence the discharge summary was sent outside the institution. Conclusions The quality of medical data captured and information management is variable across hospitals. It is recommended that medical history documentation guidelines and standardised discharge summaries be implemented in Australian healthcare services. What is known about this topic? Australia has a complex health system, the government has approved funding to develop a universal online electronic medical record system and is currently trialling this in an opt-out style in the Napean Blue Mountains (NSW) and in Northern Queensland. The system was originally named the personally controlled electronic health record but has since been changed to MyHealth Record (2016). In Victoria, there exists a wide range of electronic health records used to varying degrees, with some hospitals still relying on paper-based records and many using scanned medical records. This causes inefficiencies in the recall of patient information and can potentially lead to incidences of adverse drug events. What does this paper add? This paper supports the concept of a shared medical record system using 200 audited patient records across five Victorian metropolitan hospitals, comparing the current information systems in place for healthcare practitioners to retrieve data. This research identifies the degree of concordance between these sources of information and in doing so, areas for improvement. What are the implications for practitioners? Implications of this research are the improvements in the quality, storage and accessibility of medical data in Australian healthcare systems. This is a relevant issue in the current Australian environment where no guidelines exist across the board in medical history documentation or in the distribution of discharge summaries to other healthcare providers (general practitioners, etc).
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Leitinger, Emma J., Joanne Clifford, Michael Parker, Amanda Iacobelli, Pauline Sung, Vivien Chen, Timothy A. Brighton, et al. "Determining the Rate of Anti-PF4 Antibody Positive Results in Patients Presenting with Venous Thrombosis but a Normal Platelet Count Following ChAdOx1 Ncov-19 Astrazeneca Vaccination: An Australian Combined State Testing Centre Experience." Blood 138, Supplement 1 (November 5, 2021): 3216. http://dx.doi.org/10.1182/blood-2021-151822.
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Abstract Introduction The CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed "Thrombosis with Thrombocytopenia Syndrome" (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to platelet factor 4 (PF4)[4, 5]. TTS commonly presents with cerebral venous sinus thrombosis (CVST) or splanchnic vessel thrombosis (SVT), but outside of TTS, CVST and SVT are uncommon, with an overall incidence of less than 0.5 per 100,000 [5-7]. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are also associated with TTS, however the background incidence of venous thromboembolism (VTE) is much higher, with 1-2 events per 1000 patients per year[7, 8]. Therefore, many patients will present with new VTE and a recent exposure to the AZ vaccine, requiring consideration of investigation for TTS. Recent data suggests that PF4 antibodies can be seen in up to 8% of patients without thrombosis but following AZ vaccination[9]. We hypothesised in patients with recent AZ vaccination, new VTE but with a normal platelet count, that the incidence of a PF4 antibody is similar to this background rate of PF4 positivity. If confirmed, then presence of a normal platelet count despite new VTE and recent vaccination may exclude TTS without the need for PF4 antibody testing. We present our preliminary data on the rates of PF4 antibody positivity amongst patients with VTE, recent AZ vaccination and a normal platelet count at presentation. Aim and Methods To assess the incidence of PF4 ELISA positive results in patients with confirmed VTE, recent vaccination (within 4-42 days) with the first dose of AZ vaccine, and platelet count greater than 150x10 9/L. A retrospective audit of cases referred with suspected TTS to Monash Pathology, Melbourne, Victoria, and New South Wales Health Pathology at Royal Prince Alfred Hospital and St George Hospital sites Sydney, New South Wales, Australia, for testing for anti PF4 antibodies from 1 st April to 31 st July 2021. Patient sera were tested for the Anti-PF4 antibody using the STAGO Asserachrom HPIA IgG ELISA (Asnières sur Seine, France). For patients with a positive PF4 antibody test additional testing was sought for either the presence of platelet activating antibodies with a flow cytometry-based assay or the presence of spontaneous serotonin release without heparin in the serotonin release assay. Results From April 1 st to July 31 st 350 tests were run on 332 patients. 91 patients met our criteria, of whom 51 were female and 40 male, with a median age of 73 years. Median platelet count at presentation was 226x10 9/L, and median D dimer values were 10 times the upper limit of normal. 86 patients had either DVT, PE or both, including 2 with upper limb DVT, and 5 patients had PE with concurrent arterial events (1 axillary artery thrombosis, 3 arterial strokes, 1 coronary artery thrombosis). Further details are presented in table 1. 82 patient samples tested negative for anti-PF4 antibodies by ELISA, 5 were positive, and were 4 weak positive/equivocal (see table 2 for further details). Of the positive results, 3 had functional testing available, of which 2 were negative, and 1 showed discordant results, with a positive SRA but negative flow cytometry. None of the weak positive/equivocal cases had functional testing results available. Of the negative ELISA results, 5 patients had functional testing results available, of which 4 were negative. One of these cases had positive testing by flow cytometry, but negative by SRA (case included in table 2). Conclusion In our Australian cohort of patients with their first dose of AZ vaccine and new VTE within 4-42days, but a normal platelet count (therefore not fulfilling the clinical criteria of TTS), the incidence of a positive PF4 antibody test was 9/91 (9.9%, 95% CI 3.7-15.9%) and only one had evidence of platelet activating antibodies. This observed rate is similar to that observed in healthy patients without thrombosis who received AZ vaccination as described by Thiele et. al., 2021. Further confirmation in a larger cohort of VTE patients is required, but if confirmed, then PF4 ELISA testing in patients with VTE and normal platelet count post AZ vaccine may not be required, and should give clinicians confidence to institute routine management. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Gomes, Lianna Ghisi, Deborah Braga Pytlak, Ângela Renata Bólico do Amaral, Dábila Araújo Sônego, Samuel Monzem, Giulia Maria Dilda Campos, Marcos De Almeida Souza, Alexandre Pinto Ribeiro, Fabíola Niederauer Flôres, and Luciana Dambrósio Guimarães. "Evaluation of Postoperative Residual Analgesia of Two Solutions Used for Local Anesthesia By Tumescence In Bitches who Underwent a Unilateral Mastectomy." Acta Scientiae Veterinariae 46, no. 1 (June 28, 2018): 5. http://dx.doi.org/10.22456/1679-9216.83159.
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Background: Breast tumors are common and require surgical treatment. A mastectomy causes edema, inflammation, and moderate to severe pain; therefore, analgesics should be used efficiently during the trans- and postoperative periods. Tumescence anesthesia has been studied in veterinary medicine; however, there is limited literature on the comparison of the constituents of the different solutions and the most suitable protocol. The objective of this study was to evaluate the residual postoperative analgesia of two solutions through the Melbourne, Modified Glasgow for dogs (EGM), and Visual Analogue (EVA) scales in bitches who underwent a unilateral mastectomy.Materials, Methods & Results: Twelve bitches, weighing between 5 and 15 kilograms and aged between 5 and 13 years old, were included in the study. To determine if the animals were medically fit to undergo the procedure, they were evaluated by clinical examination, laboratory testing (complete blood count, serum biochemistry [urea, creatinine and alanine aminotransferase/ALT], and imaging (thorax x-ray and abdominal ultrasonography). Patients were randomly divided into two groups. One group received a lidocaine-containing tumescent solution (GTL) that consisted of 210 mL of lactated Ringer's solution (at a temperature between 8 and 12°C), 40 mL of 2% lidocaine hydrochloride without vasoconstrictor, and 0.5 mL of adrenaline (1 mg/mL). The other group received ropivacaine (GTR) with 233.3 mL of lactated Ringer's solution (at the same temperature as the previous group’s), 16.7 mL of ropivacaine (7.5 mg/mL), and 0.5 mL of adrenaline (1 mg/mL). Both groups received a combination of acepromazine (0.04 mg/kg) and meperidine (2 mg/kg) as preanesthetic medication (MPA), followed by induction using propofol (to effect) and maintenance using isoflurane. The solutions were infused subcutaneously (SC) 5 min after stabilization of the anesthetic plane. For the mastectomy, the solutions were distributed throughout the mammary chain to be withdrawn, starting at the thoracic and abdominal regions and ending in the inguinal region. In the postoperative period, the animals were evaluated using three different scales (Melbourne, Glasgow modified for dogs [EGM], and Visual Analogue [EVA] scales), at six time points: one, two, four, eight, 12 and 24 h after extubation, or until the time of analgesic rescue when the animal presented with a score higher than 3.33 on the EGM scale. There were no statistical differences between the groups (P > 0.05) in any of the scales evaluated; however, most of the animals demonstrated analgesic rescue in the first hour of evaluation. GTR showed an additional rescue compared to GTL.Discussion: Analgesic rescue occurred in the first hour of the postoperative period. This differs from other studies that used morphine in MPA and observed higher analgesia. This occurred because meperidine, the drug used in the study, has a shorter duration and is a less potent analgesic than morphine. We opted for this opioid because of its minimal interaction with the drug used in MPA and to better identify the residual effect of the administered solution. In addition, it does not interact with the other drugs used in the anesthetic protocol. It is known that the tumescence technique prolongs the analgesic effect of MPA because of subcutaneous absorption of a portion of the injected solution adjacent to the area being operated on. However, this was not observed as 50% of the animals in each group were rescued during the first hour of the evaluation. From this study, it was concluded that the tumescent solutions used in the trans-operative period should not be expected to have analgesic effects during the postoperative period of mastectomies because of the short duration of action.
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Kabarambi, Anita, Sheila Kansiime, Sylvia Kusemererwa, Jonathan Kitonsa, Pontiano Kaleebu, and Eugene Ruzagira. "Predictors of Loss to Follow-Up in an HIV Vaccine Preparedness Study in Masaka, Uganda." International Journal of Environmental Research and Public Health 19, no. 11 (May 24, 2022): 6377. http://dx.doi.org/10.3390/ijerph19116377.
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Background: High participant retention is essential to achieve adequate statistical power for clinical trials. We assessed participant retention and predictors of loss to follow-up (LTFU) in an HIV vaccine-preparedness study in Masaka, Uganda. Methods: Between July 2018 and March 2021, HIV sero-negative adults (18–45 years) at high risk of HIV infection were identified through HIV counselling and testing (HCT) from sex-work hotspots along the trans-African highway and fishing communities along the shores of Lake Victoria. Study procedures included collection of baseline socio-demographic data, quarterly HCT, and 6-monthly collection of sexual risk behaviour data. Retention strategies included collection of detailed locator data, short clinic visits (1–2 h), flexible reimbursement for transport costs, immediate (≤7 days) follow-up of missed visits via phone and/or home visits, and community engagement meetings. LTFU was defined as missing ≥2 sequential study visits. Poisson regression models were used to identify baseline factors associated with LTFU. Results: 672 participants were included in this analysis. Of these, 336 (50%) were female and 390 (58%) were ≤24 years. The median follow-up time was 11 months (range: 0–31 months). A total 214 (32%) participants were LTFU over 607.8 person-years of observation (PYO), a rate of 35.2/100 PYO. LTFU was higher in younger participants (18–24 years versus 35–45 years, adjusted rate ratio (aRR) = 1.29, 95% confidence interval (CI) 0.80–2.11), although this difference was not significant. Female sex (aRR = 2.07, 95% CI, 1.51–2.84), and recreational drug use (aRR = 1.61, 95% CI, 1.12–2.34) were significantly associated with increased LTFU. Engagement in transactional sex was associated with increased LTFU (aRR = 1.36, 95% CI, 0.97–1.90) but this difference was not significant. LTFU was higher in 2020–2021 (the period of COVID-19 restrictions) compared to 2018–2019 (aRR = 1.54, 1.17–2.03). Being Muslim or other (aRR = 0.68, 95% CI 0.47–0.97) and self-identification as a sex worker (aRR = 0.47, 95% CI, 0.31–0.72) were associated with reduced LTFU. Conclusion: We observed a high LTFU rate in this cohort. LTFU was highest among women, younger persons, recreational drug users, and persons who engage in transactional sex. Efforts to design retention strategies should focus on these subpopulations.
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Kati, Warren M., Debra Montgomery, Clarence Maring, Vincent S. Stoll, Vincent Giranda, Xiaoqi Chen, W. Graeme Laver, William Kohlbrenner, and Daniel W. Norbeck. "Novel α- and β-Amino Acid Inhibitors of Influenza Virus Neuraminidase." Antimicrobial Agents and Chemotherapy 45, no. 9 (September 1, 2001): 2563–70. http://dx.doi.org/10.1128/aac.45.9.2563-2570.2001.
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ABSTRACT In an effort to discover novel, noncarbohydrate inhibitors of influenza virus neuraminidase we hypothesized that compounds which contain positively charged amino groups in an appropriate position to interact with the Asp 152 or Tyr 406 side chains might be bound tightly by the enzyme. Testing of 300 α- and β-amino acids led to the discovery of two novel neuraminidase inhibitors, a phenylglycine and a pyrrolidine, which exhibited K i values in the 50 μM range versus influenza virus A/N2/Tokyo/3/67 neuraminidase but which exhibited weaker activity against influenza virus B/Memphis/3/89 neuraminidase. Limited optimization of the pyrrolidine series resulted in a compound which was about 24-fold more potent than 2-deoxy-2,3-dehydro-N-acetylneuraminic acid in an anti-influenza cell culture assay using A/N2/Victoria/3/75 virus. X-ray structural studies of A/N9 neuraminidase-inhibitor complexes revealed that both classes of inhibitors induced the Glu 278 side chain to undergo a small conformational change, but these compounds did not show time-dependent inhibition. Crystallography also established that the α-amino group of the phenylglycine formed hydrogen bonds to the Asp 152 carboxylate as expected. Likewise, the β-amino group of the pyrrolidine forms an interaction with the Tyr 406 hydroxyl group and represents the first compound known to make an interaction with this absolutely conserved residue. Phenylglycine and pyrrolidine analogs in which the α- or β-amino groups were replaced with hydroxyl groups were 365- and 2,600-fold weaker inhibitors, respectively. These results underscore the importance of the amino group interactions with the Asp 152 and Tyr 406 side chains and have implications for anti-influenza drug design.
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Osei, Wilberforce A., Tyler Shugg, Reynold C. Ly, Steven M. Bray, Benjamin A. Salisbury, Ryan R. Ratcliff, Victoria M. Pratt, Ibrahim Numanagić, and Todd Skaar. "Abstract 1151: Pharmacogenomics genotyping from clinical somatic whole exome sequencing: Aldy, a computational tool." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1151. http://dx.doi.org/10.1158/1538-7445.am2022-1151.
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Abstract Background Pharmacogenomics (PGx) testing can reduce toxicities and improve efficacy of several drugs used to treat cancer and associated symptoms. PGx results can be determined from germline whole-exome sequencing (WES), but somatic mutations may cause discordance between tumor and germline DNA. Since clinical diagnostic sequencing in oncology frequently only includes tumor DNA, there would be clinical value in calling germline PGx genotypes from tumor DNA. Thus, the purpose of this study was to assess the feasibility of using somatic WES data to call germline PGx genotypes. Methods Germline and somatic WES data were obtained as part of the clinical workflow for 64 patients treated at the solid molecular tumor board clinic at Indiana University. Aldy v3.3 was implemented in LifeOmic’s Precision Health Cloud™ to call PGx genotypes from somatic WES. Somatic Aldy calls were compared with previously validated Aldy germline calls for 8 genes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, and TPMT. Somatic read depth was >100x, except for the intronic CYP3A4*22 variant, which was >30x. Results Somatic and germline Aldy calls were compared for a total of 512 genotypes and 56 (11%) calls were discordant. Discordant calls were most common for CYP2B6 (23.4%), followed by CYP2D6 (14.1%), CYP2C19 (10.9%), CYP2C8 (6.3%), and DPYD (6.3%). In contrast, all Aldy calls were concordant for CYP3A5 and TPMT. 38 out of 64 subjects (59%) had discordant calls for at least one gene. The most common first cancer diagnoses in our cohort were colorectal (9.3%), breast (7.8%), and pancreatic (7.8%), and the rates of discordant Aldy calls did not differ by cancer type (p>0.05 for all cancer types). Based on our analyses of discordant calls, we anticipate that adjusting Aldy’s thresholds for variant calling may allow Aldy to determine genotypes from somatic WES data. Conclusion In most cases, genotype calls of drug metabolism genes from tumor DNA reflected the germline genotypes; however, additional work needs to be done to determine if the remaining discordant calls can be corrected by modifying the informatics tools or if they are due to somatic mutations. Citation Format: Wilberforce A. Osei, Tyler Shugg, Reynold C. Ly, Steven M. Bray, Benjamin A. Salisbury, Ryan R. Ratcliff, Victoria M. Pratt, Ibrahim Numanagić, Todd Skaar. Pharmacogenomics genotyping from clinical somatic whole exome sequencing: Aldy, a computational tool [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1151.
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Villaflor, Victoria, Rajwanth Veluswamy, Elena Garralda, Richard Maziarz, Emese Zsiros, Anthony Shields, Mariano Ponz-Sarvise, et al. "Abstract CT241: ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors." Cancer Research 82, no. 12_Supplement (June 15, 2022): CT241. http://dx.doi.org/10.1158/1538-7445.am2022-ct241.
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Abstract Background: AAC-HPV consists of autologous RBCs engineered using Cell Squeeze® technology to deliver synthetic long peptides (SLP) of HPV16 E6, E7 and the adjuvant, poly I:C. After intravenous (IV) administration, the AACs are designed to be phagocytosed by endogenous antigen presenting cells (APCs) and the E6 and E7 antigens presented on the APC’s major histocompatibility complexes (MHCs). The concurrent delivery of antigen and adjuvant to the APCs is designed to elicit a potent antitumor T cell response to drive HPV16+ tumor killing. Preclinical experiments demonstrated that post IV administration of mouse AAC-HPV in a HPV16 E7-expressing TC-1 mouse model, E7 specific CD8+ T cells are recruited to the tumor, inhibiting tumor growth, prolonging survival, and forming immunological memory. Murine AAC-HPV treatment was also shown to be synergistic with cisplatin combinations. In vitro studies with human volunteer derived SQZ-AAC-HPV demonstrated to be endocytosed by dendritic cells and drive IFN-gamma production by T cell clones specific to human E7. The Phase 1/2 study’s biomarker program investigates whether pharmacodynamic effects observed in nonclinical studies correlate with potential clinical benefit. Immunogenic and pharmacodynamic endpoints include quantification and characterization of TILs and tumor microenvironment, changes in numbers and functions of circulating blood cells. In addition, cytokine responses and cell-free HPV16 DNA will be measured. Methods: ENVOY-001 (NCT04892043) is open for enrollment to HLA A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors and includes escalation cohorts for monotherapy and in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitors. The study is divided in two parts, the first will assess the safety in monotherapy dose-escalation following a Bayesian Optimal Interval approach. The second part of the study will assess the safety of SQZ-AAC-HPV when combined with nivolumab 360 mg q3w and/or ipilimumab 3 mg/kg q3w x4 or 1 mg/kg q6w when combined with nivolumab. The cycle length is 3 weeks, and patients will receive SQZ-AAC-HPV for up to 1 year or until available autologous drug product is exhausted. Eligible patients including but not limited to anal, cervical and head and neck tumors will undergo a 200 mL whole blood collection at the study site. The manufacturing process takes less than 24 hours to produce multiple cryopreserve patient doses and this therapy does not necessitate pre-conditioning. The vein-to-vein time for the 1st administration is approximately one week. Patients must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Screening and on study. A Data Monitoring Committee is in place. No formal statistical hypothesis testing will be performed. Results: N/A Conclusions: N/A Citation Format: Victoria Villaflor, Rajwanth Veluswamy, Elena Garralda, Richard Maziarz, Emese Zsiros, Anthony Shields, Mariano Ponz-Sarvise, Martijn Lolkema, Mehdi Brahmi, Julia Jennings, Nathan Miselis, Lindsay Moore, Katarina Blagovic, Rui-Ru Ji, Scott Loughhead, Ricardo Zwirtes, Sandip Patel. ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT241.
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Williams, J. A. E., M. Chester-Jones, A. Francis, I. Marian, M. Goff, G. Brewer, M. Gulati, et al. "AB0980 Hand Osteoarthritis: investigating Pain Effects in a randomised placebo-controlled feasibility study of estrogen-containing therapy (HOPE-e): report on the primary feasibility outcomes." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1616.2–1617. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2437.
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BackgroundThere is an unmet need for new treatments for hand osteoarthritis (OA). Symptomatic hand OA is more common in women and its incidence increases round the age of menopause. Pre-clinical, epidemiological and post hoc studies in Hormone Replacement Therapy (HRT) trials implicate estrogen deficiency as of likely importance in OA aetiopathogenesis. No clinical trials of HRT have been carried out in hand OA to date. The licensed HRT Duavive (conjugated estrogens + SERM bazedoxifene) was selected on its potential for efficacy and tolerability.ObjectivesWe set out to determine the feasibility and acceptability of this form of HRT in post-menopausal women with hand OA, to generate proof of concept data and refine methods for a full study.MethodsISRCTN12196200. Females aged 40-65 yrs and 1-10yrs after final menstrual period with hand OA fulfilling ACR criteria and 2+ painful hand joints were recruited. Eligibility incorporated best practice for HRT prescription but did not require menopausal symptoms. Recruitment was at 3 sites in primary/secondary care, including directly from the community. Design was parallel group, double-blind 1:1 randomisation of Duavive or placebo, orally once daily for 24 weeks, then weaning for 4 weeks before stopping. Routes and rates of recruitment and the acceptability of randomisation, medication (compliance, retention), and proposed outcomes were measured, and the likelihood of unblinding. Measures related to hand pain and function, menopause symptoms and joint appearance. Patient and Public Involvement actively informed study rationale, design and materials. An end of study questionnaire and 2 participant focus groups provided further acceptability data.ResultsRecruitment was for 12/possible 18 months, interrupted due to COVID-19. Some study procedures were modified to allow reopening whilst collecting all primary outcomes. 434 enquiries/referrals were received, leading to 96 telephone pre-screens, of which 33 gave written informed consent and attended face to face screening. 28/33 screened (85%) were eligible and randomised. The highest number of randomisations was from study web presence (n=7) followed by SMS text from GP surgeries (n=5). Of 401 not proceeding, 250 (62%) were ineligible, most commonly due to contraindicated medication, followed by medical contraindication, whilst 55 (14%) decided not to take part, for reasons including not wanting to take a hormone-based drug or difficulty attending study visits. Retention and compliance were excellent. All 28 participants completed all study follow ups, with only 3 withdrawals from treatment due to AEs, 2 of these at week 24 and all in the placebo arm. There were no serious AEs. High levels of completeness of all study outcome measures were achieved. Bang’s blinding index suggested that participants/investigators were well blinded. There were overall high/good levels of satisfaction with taking part in the study. 26/28 (92%) would recommend taking part to others with hand OA (irrespective of study arm). Many found the flexibility offered by a combination of remote and face to face visits (due to the pandemic) attractive. Additional insights from focus groups were to include hand stiffness as well as pain measures but to reduce the overall number of questions.ConclusionDespite COVID-19 and a reduced recruitment period, this study recruited sufficient numbers to assess feasibility outcomes. Randomisation of eligible people and retention rates were high. A mixture of remote and face to face visits due to COVID-19 probably improved recruitment and retention and was supported by participants, who were generally satisfied with the study design and medication. The study provided useful insight and improvements that would be incorporated into a future study. Overall, this feasibility study showed that with clear messaging on eligibility and a defined recruitment strategy, recruitment and retention to a study testing this treatment is possible.AcknowledgementsThis research was funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0416-20023). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The study team thank the sites and the participants who made this research possible.Disclosure of InterestsJennifer A.E. Williams: None declared, Mae Chester-Jones: None declared, Anne Francis: None declared, Ioana Marian: None declared, Megan Goff: None declared, Gretchen Brewer: None declared, Malvika Gulati: None declared, Lucy Eldridge: None declared, Patrick Julier: None declared, Catherine Minns Lowe: None declared, Vicki Barber: None declared, Victoria Glover: None declared, Charles Mackworth-Young: None declared, Tonia Vincent Consultant of: Pfizer, Grant/research support from: Grant support from Fidia, Biosplice, Novartis, Pfizer as part of their contribution to an international consortium., Sarah E Lamb: None declared, Katy Vincent: None declared, Susan J Dutton: None declared, Fiona E Watt Consultant of: Pfizer, Grant/research support from: Pfizer and from Astellas Pharma (> 3 years ago)
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Garcia-Delgado, Regina, Donal P. McLornan, László Rejtő, Eric Jourdan, Haifa Kathrin Al-Ali, Andrzej Pluta, Marek Hus, et al. "An Open-Label, Phase 2 Study of KRT-232, a First-in-Class, Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients with Myelofibrosis (MF) Who Have Previously Received Treatment with a JAK Inhibitor." Blood 134, Supplement_1 (November 13, 2019): 2945. http://dx.doi.org/10.1182/blood-2019-123836.
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Background: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by progressive bone marrow fibrosis, ineffective erythropoiesis, dysplastic megakaryocyte hyperplasia, and extramedullary hematopoiesis. MF includes primary MF (PMF), post-polycythemia vera MF (post-PV-MF), and post-essential thrombocythemia MF (post-ET-MF). Clinical presentation is heterogeneous, marked by splenomegaly, progressive anemia, and constitutional symptoms. The median survival in patients with high-risk disease is approximately 2 years. Hematopoietic Stem Cell Transplant (HSCT) is a potentially curative therapy, however due to considerable morbidity and mortality rates, HSCT is not appropriate for most patients, including elderly patients with intermediate-II and high-risk disease. The Janus kinase (JAK) inhibitor ruxolitinib is approved in the US and EU for the treatment of patients with intermediate or high-risk MF, including PMF, post-PV-MF, and post-ET-MF. In clinical studies, treatment with ruxolitinib has been shown to reduce spleen volume by International Working Group (IWG) criteria in approximately 28% to 42% of patients and improve constitutional symptoms of MF in approximately 46% of patients (Verstovsek, J Hematol Oncol. 2017). Ruxolitinib provides symptomatic improvement, however, does not target the malignant clone or appreciably reduce the degree of fibrosis; some patients experience disease progression and leukemic transformation while on therapy (Versotvsek, NEJM. 2010; Harrison, NEJM. 2012; Kremyanskaya, Br J Hem. 2014). Moreover, ruxolitinib is associated with AEs including anemia and thrombocytopenia, which can lead to discontinuation. Approximately 50% of patients treated with ruxolitinib discontinued treatment within 3 years and 73% at 5 years (Verstovsek, Haematologica. 2015; Verstovsek, J Hematol Oncol. 2017; Cervantes, Blood. 2013; Harrison, Leukemia. 2016). Median overall survival in patients who discontinue ruxolitinib is 14-16 months, highlighting the need for novel therapies targeting alternative pathways in the setting of failure or intolerance of JAK inhibitor therapy (Newberry, Blood. 2017). The tumor suppressor protein p53 is the master regulator of cell-cycle arrest and apoptosis in response to cellular stress or DNA damage. Murine double minute 2 (MDM2) is a key regulator of p53, inhibiting its activity via ubiquitination, nuclear export, and direct inhibition of transcriptional activity. Increased MDM2 protein expression has been observed in MF CD34+ cells, suggesting that MF might be sensitive to MDM2 inhibition (Lu M, Blood. 2017). KRT-232 is a potent and selective, oral, small molecule drug that targets MDM2 and prevents MDM2-mediated p53 inhibition, allowing p53 to mediate tumor cell-cycle arrest and apoptosis. In MF, TP53 is observed to be wild-type in 96% of MF patients, suggesting MDM2 inhibition could be a successful therapeutic strategy in this disease (Raza, Am J Hematol. 2012). KRT-232 has been investigated as monotherapy and in combination with trametinib or dabrafenib in phase I studies of AML and melanoma; the most common treatment-related adverse events (TRAEs) observed were nausea, diarrhea, vomiting, decreased appetite, anemia, leukopenia, thrombocytopenia, and fatigue. The majority of TRAEs were grade 1 or 2. Methods: KRT-232 is being evaluated in an open-label phase 2 study in patients with MF who relapsed on or are refractory to JAK inhibitors (Figure). Up to 247 patients ≥ 18 years of age, with ECOG performance status ≤ 2, with high-, intermediate-2, or intermediate-1 risk disease by Dynamic International Prognostic System (DIPSS), and failure of prior treatment with JAK inhibitors will be enrolled. The study will be conducted in 2 parts. Part A will identify the recommended dose and schedule by testing varying doses and schedules across 7 treatment cohorts. Part B will evaluate safety and efficacy using the recommended dose and schedule from Part A. The primary endpoint of the study is to determine spleen response at week 24; secondary endpoints include improvement in MPN-SAF Total Symptom Score (weeks 24 and 48), red blood cell (RBC) transfusion independence, and rates of complete remission and partial remission (IWG-ERT and ELN) at week 24. This trial is enrolling at multiple sites in the United States and Europe (NCT03662126, EudraCT: 2018-001671-21). Disclosures Garcia-Delgado: Hospital Virgen De La Victoria Malaga: Employment; Novartis: Consultancy, Speakers Bureau; Celgene: Speakers Bureau. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria. Jourdan:Novartis: Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Al-Ali:Celgene: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CTI: Honoraria. Pluta:Freelight Poland: Honoraria; Sandoz: Honoraria; Servier: Honoraria; Jansen-Cilag: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Roche: Honoraria; Specialistic Hospital in Brzozow,Dept of Haematooncology Ks.Bielawskiego 18 36-200 Brzozow, Poland: Employment; Teva: Honoraria; Roche Poland: Membership on an entity's Board of Directors or advisory committees; Jansen Cilag Poland: Membership on an entity's Board of Directors or advisory committees. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . Khan:Amgen: Consultancy; Celgene: Consultancy; Incyte: Honoraria; Pfizer: Consultancy; Takeda: Research Funding. Jost:Novartis: Research Funding; Celgene: Other: Travel Support; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Abbvie: Consultancy, Patents & Royalties: Royalty payments for the drug compound ABT-199, Research Funding; Bohringer: Consultancy, Research Funding; BMS: Consultancy, Speakers Bureau. Rothbaum:Kartos Therapeutics: Employment, Patents & Royalties: Pending; Quogue Bioventures LLC: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. McGreivy:Kartos Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Verstovsek:Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. OffLabel Disclosure: Yes, KRT-232 is an investigational small molecule MDM2 inhibitor. This trial-in-progress abstract describes a registered clinical trial that will evaluate the safety and efficacy of KRT-232 for patients with myelofibrosis.
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Gotlib, Jason, Nashat Gabrail, Casey L. O'Connell, Regina Garcia-Delgado, Timothy Sbardellati, Wayne M. Rothbaum, Jesse McGreivy, Claire N. Harrison, and Jean-Jacques Kiladjian. "A Randomized, Open-Label, Multicenter, Phase 2 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared with Ruxolitinib in Patients with Phlebotomy-Dependent Polycythemia Vera." Blood 134, Supplement_1 (November 13, 2019): 4168. http://dx.doi.org/10.1182/blood-2019-123546.
Full textAbstract:
Background: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by clonal stem cell proliferation of the erythroid, myeloid, and megakaryocytic lines. The predominant clinical characteristic is an increase in red cell mass, resulting in hyperviscosity of the blood, which is responsible for most symptoms during early stages of disease. Disease progression typically results in symptomatic splenomegaly and severe constitutional symptoms, causing significant morbidity and a shortened life expectancy. Patients with PV may develop cardiovascular complications, myelofibrosis (MF), myelodysplasia, or acute myeloid leukemia (AML). Long-term (20-year) survival for PV is 18%, highlighting the poor long-term prognosis and need for additional therapies. Phlebotomy and low-dose aspirin are the standard of care for initial treatment; hydroxyurea (HU) remains the myelosuppressive agent of choice, despite the increased potential for leukemic transformation, estimated at 10% after 13 years of exposure. The Janus kinase (JAK) inhibitor ruxolitinib is approved in the US and Europe for the treatment of patients who have had an inadequate response to or are intolerant of HU. In clinical trials, ruxolitinib produced responses in 23% of patients, compared with <1% in patients receiving best available therapy (Verstovsek, et al. Haematologica. 2016). Despite this significant improvement, there remains a substantial unmet need for patients with PV who are resistant to or intolerant of HU. The tumor suppressor protein p53 is the master regulator of cell-cycle arrest and apoptosis in response to cellular stress or DNA damage. Murine double minute 2 (MDM2) is a key regulator of p53, inhibiting its activity via ubiquitination, nuclear export, and direct inhibition of transcriptional activity. MDM2 is upregulated in PV CD43+ stem/progenitor cells, making the p53-MDM2 axis an attractive target in PV. In PV, TP53 is observed to be wild-type in 94% of patients, suggesting MDM2 inhibition as a potentially successful strategy (Raza, et al. Am. J. Hematol. 2012). KRT-232 is a potent and selective oral small-molecule drug that targets MDM2 and prevents MDM2-mediated p53 inhibition, allowing p53 to mediate tumor cell-cycle arrest and apoptosis. In a phase 1 dose-finding study, clinical responses were observed in 7/12 (58%) of PV patients treated with an alternative MDM2 inhibitor (Mascarenhas, et al. Blood, 2019). KRT-232 has been investigated as monotherapy and in combination with trametinib or dabrafenib in phase I studies of AML and melanoma; the most common treatment-related adverse events (TRAEs) observed in these studies were nausea, diarrhea, vomiting, decreased appetite, anemia, leukopenia, thrombocytopenia, and fatigue. The majority of TRAEs were grade 1 or 2. Methods: This randomized, open-label study aims to evaluate the efficacy, safety, and pharmacokinetics of KRT-232 compared with ruxolitinib in up to 320 patients with phlebotomy-dependent PV (Figure). The study will be conducted in 2 parts. Part A will identify the recommended dose and schedule by testing 4 treatment cohorts. In Part B, patients will be randomized 1:1 to either KRT-232 or ruxolitinib in order to evaluate safety and efficacy using the recommended dose/schedule for KRT-232 from part A. This study will enroll patients ≥ 18 years of age with PV and an ECOG performance status ≤ 2. In Part A, patients who are phlebotomy dependent with and without splenomegaly are eligible and patients must be resistant to or intolerant of HU or have undergone treatment with interferon. In Part B, only phlebotomy-dependent patients with splenomegaly are eligible, and patients must be resistant or intolerant to HU. The primary endpoint is proportion of patients with splenomegaly achieving a response at Week 32, defined as having achieved both of the following: 1) the absence of phlebotomy eligibility from Week 8 through Week 32, with no more than one phlebotomy eligibility occurring after randomization and before the Week 8 visit and 2) a reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 32. Secondary endpoints include response rate, duration of response and improvement in patient-reported outcomes. Exploratory endpoints include molecular and biomarker analysis including TP53 mutational status. This trial is enrolling at multiple sites in the United States and Europe (NCT03669965, EduraCT: 2018-001672-38). Figure Disclosures Gotlib: Deceiphera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Promedior: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicines: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Allakos: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. O'Connell:Pfizer: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding. Garcia-Delgado:Celgene: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Hospital Virgen De La Victoria Malaga: Employment. Sbardellati:Kartos Therapeutics: Employment, Equity Ownership. Rothbaum:Kartos Therapeutics: Employment, Patents & Royalties: Pending; Quogue Bioventures LLC: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. McGreivy:Kartos Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Harrison:Janssen: Speakers Bureau; Gilead: Speakers Bureau; CTI: Speakers Bureau; Roche: Honoraria; Sierra Oncology: Honoraria; AOP: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Promedior: Honoraria; Shire: Speakers Bureau; Incyte: Speakers Bureau. Kiladjian:AOP Orphan: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Consultancy. OffLabel Disclosure: Yes, KRT-232 is an investigational small molecule MDM2 inhibitor. This trial-in-progress abstract describes a registered clinical trial that will evaluate the safety and efficacy of KRT-232 for patients with polycythemia vera.
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Ruseckaite, Rasa, Sue Evans, Jeremy Millar, Sara Holton, Danielle Mazza, Jane Fisher, and Maggie Kirkman. "GPs’ Insights into Prostate Cancer Diagnosis and Care in Regional Victoria, Australia." Qualitative Report, December 22, 2016. http://dx.doi.org/10.46743/2160-3715/2016.2540.
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The aim of this research was to ascertain General Practitioners’ (GPs) perceptions and experiences of prostate cancer (PCa) diagnosis, treatment, and care in metropolitan Melbourne and in a regional area of Victoria, Australia, associated with poorer PCa outcomes. Semi-structured qualitative interviews were conducted with GPs (N= 10) practising in the selected region and in metropolitan Melbourne, Australia. GPs thought that most men wanted PSA testing and were willing to undergo rectal examination. Some GPs were troubled by inconsistent screening guidelines from different professional bodies. They identified a need for resources to support them in educating patients about PCa. GPs thought it might be more difficult for young female GPs to care for patients in relation to PCa screening; differences were evident between younger female GPs and older male GPs in the approach they adopted in interviews. Regional GPs often referred patients to services in larger centres because no local specialists were available. GPs also found it hard to explain differences in PCa outcomes in regional and metropolitan areas. Potential age and gender differences in GPs in relation to prostate care warrant further examination. Although GPs were able to offer only limited insights into the poorer outcomes in regional areas, they identified ways in which they could be assisted to provide best-practice care. Multidisciplinary care, resources for patients, and consistent guidelines for the detection and treatment of PCa should contribute to better care in all areas.
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Boretti, Alberto. "The increasing number of infected in Victoria, Australia since June 15, 2020, is the result of over-testing and over-controlling without safety." Integrative Journal of Medical Sciences 7 (August 3, 2020). http://dx.doi.org/10.15342/ijms.7.187.
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On June 27, 2020, when return to normality was expected, the Victorian government and the mainstream media claimed the existence of “hot spots” of Covid19 infection in Victoria, Australia. This claim was an artifact of the much larger number of tests conducted in the most disadvantaged suburbs of Melbourne to detect an increased number of cases. The rate of positive cases detected over the number of tests performed to achieve this result was stable at about 0.3%, which is the rate experienced in Victoria since the outbreak in March, despite the focus on the areas where positive higher rates were likely. The restrictions have then been made harsher, rather than more relaxed in this state, and return to normality is now suffering nationwide. With a total number of fatalities stable at 104 in a country of more than 25 million people, when the normal flu may take 3,000 people per year, the epidemiological management of the Covid19 infection after more than 4 months of restrictions resembles an Orwellian dystopia more than a correct epidemiological approach.
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Edwards, Ian. "Methodological Trends in Investigations into Ancient Pottery From the Levant." MRS Proceedings 185 (1990). http://dx.doi.org/10.1557/proc-185-543.
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AbstractThe Australian excavations at Pella in Jordan under the guidance of Professor Basil Hennessy (Sydney University, Australia) have over the past 13 years demonstrated the current range of methodologies used in pottery studies in the Levant. One feature of the Australian field team has been the continuing inclusion of this writer from the Archaeology Research Unit, Victoria College, Melbourne (ARU) as a ceramic technologist/potter.The ARU at Victoria College, which operates together with a practical pottery workshop and an Advanced Ceramic Mlaterials Development Unit, uses a multidisciplinary team approach to look at excavated ancient pottery not primarily as archaeological artefacts but as pottery.Within the ARU Dr Ralph Segnit handles the mineralogy, Dr John Hamilton the geology, while Robert Hughan, to whom I am indebted for the testing reported here, handles the ceramic chemistry and fracture mechanics aspects. My role as both a ceramic technologist involved in field archaeology and as a trained potter, is to participate in generating the questions which will form the focus of the team's investigations.
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Barratt, Monica J., Stephen J. Bright, and Ash R. Blackwell. "Community-led guerrilla drug checking in response to deaths from adulterated MDMA in Victoria, Australia." Drugs, Habits and Social Policy, August 17, 2022. http://dx.doi.org/10.1108/dhs-01-2022-0006.
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Purpose Following deaths and hospitalisations in Melbourne, Victoria, Australia, related to the unwitting consumption of a combination of 25C-NBOMe and 4-FA, a community-led unauthorised drug checking service was rapidly established at a subsequent music festival. We aim to demonstrate the value of community-led drug checking, even when conducted in less-than-ideal conditions, by describing this service and reporting on its outcomes. Design/methodology/approach In all, 131 samples were tested with between 1 and 4 (M = 2.24 and SD = 0.61) reagents (Mandelin, Marquis, Mecke and Simons), and behavioural intentions of service users were reported. Findings People whose results indicated that the drug tested was what they expected, or was a drug familiar to them, were more likely to report an intention to take the drug compared to those whose results indicated that the drug was not what they had expected. For example, in 11 cases where the expected substance was not identified and novel substances including 2 C-X (including the NBOMe series), methylone, mephedrone, PMA and MXE were indicated, most reported an intention to discard (8/11). Practical implications The guerrilla service appeared to dissuade some people from consuming substances with higher risk profiles. It was also quick to identify substances of concern consistent with the NBOMe/4-FA combination for broader community action. The authors urge governments in Australia and elsewhere to reconsider their opposition to drug checking services, given their utility as vital health services during times of volatile drug market shifts. Originality/value While these data are five years old, it has only been in the past year that the Coroners Court of Victoria finalised their report on the deaths associated with this drug outbreak, providing context for the rapid peer response.