37 research outputs found

    Federal and state cooperation necessary but not sufficient for effective regional mental health systems : insights from systems modelling and simulation

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    For more than a decade, suicide rates in Australia have shown no improvement despite significant investment in reforms to support regionally driven initiatives. Further recommended reforms by the Productivity Commission call for Federal and State and Territory Government funding for mental health to be pooled and new Regional Commissioning Authorities established to take responsibility for efficient and effective allocation of ‘taxpayer money.’ This study explores the sufficiency of this recommendation in preventing ongoing policy resistance. A system dynamics model of pathways between psychological distress, the mental health care system, suicidal behaviour and their drivers was developed, tested, and validated for a large, geographically diverse region of New South Wales; the Hunter New England and Central Coast Primary Health Network (PHN). Multi-objective optimisation was used to explore potential discordance in the best-performing programs and initiatives (simulated from 2021 to 2031) across mental health outcomes between the two state-governed Local Health Districts (LHDs) and the federally governed PHN. Impacts on suicide deaths, mental health-related emergency department presentations, and service disengagement were explored. A combination of family psychoeducation, post-attempt aftercare, and safety planning, and social connectedness programs minimises the number of suicides across the PHN and in the Hunter New England LHD (13.5% reduction; 95% interval, 12.3–14.9%), and performs well in the Central Coast LHD (14.8% reduction, 13.5–16.3%), suggesting that aligned strategic decision making between the PHN and LHDs would deliver substantial impacts on suicide. Results also highlighted a marked trade-off between minimising suicide deaths versus minimising service disengagement. This is explained in part by the additional demand placed on services of intensive suicide prevention programs leading to increases in service disengagement as wait times for specialist community based mental health services and dissatisfaction with quality of care increases. Competing priorities between the PHN and LHDs (each seeking to optimise the different outcomes they are responsible for) can undermine the optimal impact of investments for suicide prevention. Systems modelling provides essential regional decision analysis infrastructure to facilitate coordinated federal and state investments for optimal impacts

    Long term cause specific mortality among 34 489 five year survivors of childhood cancer in Great Britain:population based cohort study

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    Objective To determine whether modern treatments for cancer are associated with a net increased or decreased risk of death from neoplastic and non-neoplastic causes among survivors of childhood cancer. Design Population based cohort study. Setting British Childhood Cancer Survivor Study. Participants Nationwide population based cohort of 34 489 five year survivors of childhood cancer with a diagnosis from 1940 to 2006 and followed up until 28 February 2014. Main outcome measures Cause specific standardised mortality ratios and absolute excess risks are reported. Multivariable Poisson regression models were utilised to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity or trend. Results Overall, 4475 deaths were observed, which was 9.1 (95% confidence interval 8.9 to 9.4) times that expected in the general population, corresponding to 64.2 (95% confidence interval 62.1 to 66.3) excess deaths per 10 000 person years. The number of excess deaths from all causes declined among those treated more recently; those treated during 1990-2006 experienced 30% of the excess number of deaths experienced by those treated before 1970. The corresponding percentages for the decline in excess deaths from recurrence or progression and non-neoplastic causes were 30% and 60%, respectively. Among survivors aged 50-59 years, 41% and 22% of excess deaths were attributable to subsequent primary neoplasms and circulatory conditions, respectively, whereas the corresponding percentages among those aged 60 years or more were 31% and 37%. Conclusions The net effects of changes in cancer treatments, and surveillance and management for late effects, over the period 1940 to 2006 was to reduce the excess number of deaths from both recurrence or progression and non-neoplastic causes among those treated more recently. Among survivors aged 60 years or more, the excess number of deaths from circulatory causes exceeds the excess number of deaths from subsequent primary neoplasms. The important message for the evidence based surveillance aimed at preventing excess mortality and morbidity in survivors aged 60 years or more is that circulatory disease overtakes subsequent primary neoplasms as the leading cause of excess mortality

    Fertility preservation for male patients with childhood, adolescent, and young adult cancer:recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

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    Item does not contain fulltextMale patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life

    Counseling and surveillance of obstetric risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

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    Female childhood, adolescent, and young adult cancer survivors have an increased risk of adverse pregnancy outcomes related to their cancer- or treatment-associated sequelae. Optimal care for childhood, adolescent, and young adult cancer survivors can be facilitated by clinical practice guidelines that identify specific adverse pregnancy outcomes and the clinical characteristics of at-risk subgroups. However, national guidelines are scarce and vary in content. Here, the International Late Effects of Childhood Cancer Guideline Harmonization Group offers recommendations for the counseling and surveillance of obstetrical risks of childhood, adolescent, and young adult survivors. A systematic literature search in MEDLINE database (through PubMed) to identify all available evidence published between January 1990 and December 2018. Published articles on pregnancy and perinatal or congenital risks in female cancer survivors were screened for eligibility. Study designs with a sample size larger than 40 pregnancies in childhood, adolescent, and young adult cancer survivors (diagnosed before the age of 25 years, not pregnant at that time) were eligible. This guideline from the International Late Effects of Childhood Cancer Guideline Harmonization Group systematically appraised the quality of available evidence for adverse obstetrical outcomes in childhood, adolescent, and young adult cancer survivors using Grading of Recommendations Assessment, Development, and Evaluation methodology and formulated recommendations to enhance evidence-based obstetrical care and preconception counseling of female childhood, adolescent, and young adult cancer survivors. Healthcare providers should discuss the risk of adverse obstetrical outcomes based on cancer treatment exposures with all female childhood, adolescent, and young adult cancer survivors of reproductive age, before conception. Healthcare providers should be aware that there is no evidence to support an increased risk of giving birth to a child with congenital anomalies (high-quality evidence). Survivors treated with radiotherapy to volumes exposing the uterus and their healthcare providers should be aware of the risk of adverse obstetrical outcomes such as miscarriage (moderate-quality evidence), premature birth (high-quality evidence), and low birthweight (high-quality evidence); therefore, high-risk obstetrical surveillance is recommended. Cardiomyopathy surveillance is reasonable before pregnancy or in the first trimester for all female survivors treated with anthracyclines and chest radiation. Female cancer survivors have increased risks of premature delivery and low birthweight associated with radiotherapy targeting the lower body and thereby exposing the uterus, which warrant high-risk pregnancy surveillance

    Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

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    Funding: RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (grant no: 098522), https://wellcome.ac.uk/what-we-do/directories/intermediate-clinical-fellowships-people-funded. TWK is supported by Engineering and Physical Sciences Research Council grant EP/P015638/1, http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/P015638/1.The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.Publisher PDFPeer reviewe

    An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

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    The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60

    Sertoli cells maintain leydig cell number and peritubular myoid cell activity in the adult mouse testis

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    The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR) specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health

    Measurement of jet fragmentation in Pb+Pb and pppp collisions at sNN=2.76\sqrt{{s_\mathrm{NN}}} = 2.76 TeV with the ATLAS detector at the LHC

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