Advancing women in medical leadership Learoyd, Diana L; Holmes‐Walker, Jane
Medical journal of Australia,
March 2020, 2020-03-00, 20200301, Volume:
212, Issue:
4
Journal Article
Peer reviewed
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary Background The management of depression in patients with poor prognosis cancers, such as lung cancer, creates specific challenges. We aimed to assess the efficacy of an integrated treatment ...programme for major depression in patients with lung cancer compared with usual care. Methods Symptom Management Research Trials (SMaRT) Oncology-3 is a parallel-group, multicentre, randomised controlled trial. We enrolled patients with lung cancer and major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with lung cancer treatment programme or usual care by a database software algorithm that used stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. Depression care for people with lung cancer is a manualised, multicomponent collaborative care treatment that is systematically delivered by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. The primary outcome was depression severity (on the Symptom Checklist Depression Scale SCL-20, range 0–4) averaged over the patient's time in the trial (up to a maximum of 32 weeks). Trial statisticians and data collection staff were masked to treatment allocation, but patients and clinicians could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN75905964. Findings 142 participants were recruited between Jan 5, 2009, and Sept 9, 2011; 68 were randomly allocated to depression care for people with lung cancer and 74 to usual care. 43 (30%) of 142 patients had died by 32 weeks, all of which were cancer-related deaths. No intervention-related serious adverse events occurred. 131 (92%) of 142 patients provided outcome data (59 in the depression care for people with lung cancer group and 72 in the usual care group) and were included in the intention-to-treat primary analysis. Average depression severity was significantly lower in patients allocated to depression care for people with lung cancer (mean score on the SCL-20 1·24 SD 0·64) than in those allocated to usual care (mean score 1·61 SD 0·58); difference −0·38 (95% CI −0·58 to −0·18); standardised mean difference −0·62 (95% CI −0·94 to −0·29). Self-rated depression improvement, anxiety, quality of life, role functioning, perceived quality of care, and proportion of patients achieving a 12-week treatment response were also significantly better in the depression care for people with lung cancer group than in the usual care group. Interpretation Our findings suggest that major depression can be treated effectively in patients with a poor prognosis cancer; integrated depression care for people with lung cancer was substantially more efficacious than was usual care. Larger trials are now needed to estimate the effectiveness and cost-effectiveness of this care programme in this patient population, and further adaptation of the treatment will be necessary to address the unmet needs of patients with major depression and even shorter life expectancy. Funding Cancer Research UK and Chief Scientist Office of the Scottish Government.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Ddi1/DDI2 proteins are ubiquitin shuttling factors, implicated in a variety of cellular functions. In addition to ubiquitin-binding and ubiquitin-like domains, they contain a conserved region ...with similarity to retroviral proteases, but whether and how DDI2 functions as a protease has remained unknown. Here, we show that DDI2 knockout cells are sensitive to proteasome inhibition and accumulate high-molecular weight, ubiquitylated proteins that are poorly degraded by the proteasome. These proteins are targets for the protease activity of purified DDI2. No evidence for DDI2 acting as a de-ubiquitylating enzyme was uncovered, which could suggest that it cleaves the ubiquitylated protein itself. In support of this idea, cleavage of transcription factor NRF1 is known to require DDI2 activity in vivo. We show that DDI2 is indeed capable of cleaving NRF1 in vitro but only when NRF1 protein is highly poly-ubiquitylated. Together, these data suggest that DDI2 is a ubiquitin-directed endoprotease.
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•DDI2 KO cells accumulate highly ubiquitylated proteins that are slowly degraded•DDI2 KO cells are hypersensitive to pharmacological proteasome inhibition•Purified DDI2 protein can directly cleave the highly ubiquitylated proteins in vitro•DDI2 site-specifically cuts NRF1 in vitro but only if NRF1 is poly-ubiquitylated
Dirac-Svejstrup et al. show that DDI2 knockout cells accumulate highly ubiquitylated proteins that are difficult to degrade and that these cells are hypersensitive to pharmacological proteasome inhibition. The DDI2 protein can directly cleave the highly ubiquitylated proteins in vitro and does this site specifically in the ubiquitylated transcription factor NRF1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess ...the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer. Methods We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56·6 (SD 11·9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225. Findings Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0·34 (95% CI 0·13–0·55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional £5278 (US$10 556) per quality-adjusted life-year gained. Interpretation The intervention—Depression Care for People with Cancer—offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective. Funding Cancer Research UK.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Like the United Kingdom and New Zealand, all eight Australian jurisdictions have legal provisions for the full-time accommodation of young children with their mothers in prison. Whether and how these ...laws are enacted varies, and there are no national or international norms. This article integrates a review of policies, principles and operating models with findings from a qualitative study, to describe the current landscape in residential programmes for mothers and children in Australian prisons. It demonstrates how current ideologies limit the system’s ability to meet the needs of imprisoned mothers, their children and prison staff. Three issues emerge as problematic: the separation of the rights and interests of mothers and children; over-reliance on attachment theory as both rationale and evidence base; and the individualization of responsibility and risk. The study is of international relevance because these themes and concepts are recognizable elsewhere, including the United Kingdom, New Zealand and some European countries.
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NUK, OILJ, PRFLJ, SAZU, UKNU, UL, UM, UPUK
To describe the implementation of a collaborative care (CC) screening and treatment program for major depression in people with cancer, found to be effective in clinical trials, into routine ...outpatient care of a cancer center.
A mixed-methods observational study guided by the RE-AIM implementation framework using quantitative and qualitative data collected over five years.
Program set-up took three years and required more involvement of CC experts than anticipated. Barriers to implementation were uncertainty about whether oncology or psychiatry owned the program and the hospital's organizational complexity. Selecting and training CC team members was a major task. 90% (14,412/16,074) of patients participated in depression screening and 61% (136/224) of those offered treatment attended at least one session. Depression outcomes were similar to trial benchmarks (61%; 78/127 patients had a treatment response). After two years the program obtained long-term funding. Facilitators of implementation were strong trial evidence, effective integration into cancer care and ongoing clinical and managerial support.
A CC program for major depression, designed for the cancer setting, can be successfully implemented into routine care, but requires time, persistence and involvement of CC experts. Once operating it can be an effective and valued component of medical care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
19.
Sexual identity in congenital adrenal hyperplasia Bosi, Isabelle ML; Holmes‐Walker, Jane; Lau, Namson S ...
Journal of paediatrics and child health,
April 2021, 2021-04-00, 20210401, Volume:
57, Issue:
4
Journal Article
Peer reviewed
Article Note: Conflict of interest: None declared. Byline: Isabelle ML Bosi, Jane Holmes-Walker, Namson S Lau, Slavica Bate, Gail Anderson, Michael Kohn, Simon Clarke
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Studies from the United States and the United Kingdom have found that imprisoned women are less likely to experience poorer maternal and perinatal outcomes than other disadvantaged women. This ...population-based study used both community controls and women with a history of incarceration as a control group, to investigate whether imprisoned pregnant women in New South Wales, Australia, have improved maternal and perinatal outcomes.
Retrospective cohort study using probabilistic record linkage of routinely collected data from health and corrective services in New South Wales, Australia. Comparison of the maternal and perinatal outcomes of imprisoned pregnant women aged 18-44 years who gave birth between 2000-2006 with women who were (i) imprisoned at a time other than pregnancy, and (ii) community controls.
onset of labour, method of birth, pre-term birth, low birthweight, Apgar score, resuscitation, neonatal hospital admission, perinatal death.
Babies born to women who were imprisoned during pregnancy were significantly more likely to be born pre-term, have low birthweight, and be admitted to hospital, compared with community controls. Pregnant prisoners did not have significantly better outcomes than other similarly disadvantaged women (those with a history of imprisonment who were not imprisoned during pregnancy).
In contrast to the published literature, we found no evidence that contact with prison health services during pregnancy was a "therapunitive" intervention. We found no association between imprisonment during pregnancy and improved perinatal outcomes for imprisoned women or their neonates. A history of imprisonment remained the strongest predictor of poor perinatal outcomes, reflecting the relative health disadvantage experienced by this population of women.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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