Search

BACKGROUND: Real-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020. METHODS: We reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS). RESULTS: As of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001). CONCLUSION: Clinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context.

Supported by clinical trial proven survival benefit, clinical guidelines recommend upfront autologous stem cell transplantation (ASCT) for eligible MM patients. However, reported real-world utilisation is lower than expected (40–60%). We reviewed ASCT utilisation, demographics and outcomes for MM patients (≤70 years, ≥12-month follow-up) enroled onto the Australian/New Zealand MRDR from June 2012 to May 2020. In 982 patients (

Summary Background Sepsis is a serious global health issue and a major cause of death and disability. The availability of a simple, community-based preventive strategy could substantially reduce the burden of sepsis. We aimed to establish whether low-dose aspirin reduced deaths or hospital admissions associated with sepsis in older people. Methods ANTISEPSIS was a substudy of ASPREE (a randomised controlled primary prevention trial of low-dose aspirin [100 mg per day] compared with placebo in community dwelling older adults conducted in Australia and the USA), with the Australian cohort included in the ANTISEPSIS substudy. Inclusion criteria were participants aged at least 70 years who did not have major illnesses. Participants were block randomised (1:1) via a centralised web portal and stratified by general practice and age. Participants, investigators, and staff were masked to the intervention. Teams of clinical specialist investigators assessed potential sepsis events to establish if they satisfied the primary endpoint of death associated with sepsis. The analyses were by intention-to-treat with univariate survival analysis methods, the log-rank test, and Cox proportional hazards regression. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000349741. Results Between March 10, 2010, and Dec 24, 2014, of 20 288 individuals assessed for eligibility, 16 703 participants aged 70 years and older at trial entry were enrolled and followed up for a median of 4·6 years (IQR 3·6–5·6). 8322 (49·8%) participants were assigned to receive aspirin and 8381 (50·2%) to placebo. 203 deaths were considered to be associated with sepsis. Univariate analysis showed similar rates of death associated with sepsis in the two study groups (hazard ratio for aspirin vs placebo 1·08, 95% CI 0·82–1·43; p=0·57). Adverse events were previously reported in the ASPREE trial. Interpretation Daily low-dose aspirin treatment did not reduce deaths associated with sepsis in community dwelling older adults. Our findings do not support the use of aspirin as a primary prevention strategy to reduce the burden of sepsis in this population. Funding National Health and Medical Research Council of Australia, National Institutes of Health, Monash University.

We read with interest the study from Rampotas et al (1) where they evaluated 158 transplant-non-eligible newly diagnosed myeloma patients treated with bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) chemotherapy. They showed that fixed duration VCD led to an overall response rate (ORR) of 72% and was 'reasonably well tolerated'. They concluded that the comparatively poor event free survival (EFS) may be improved "with the use of higher cumulative bortezomib" doses.

Background Aboriginal and Torres Strait Islander women experience high rates of diabetes in pregnancy (DIP), contributing to health risks for mother and infant, and the intergenerational cycle of diabetes. By enhancing diabetes management during pregnancy, postpartum and the interval between pregnancies, the DIP Partnership aims to improve health outcomes and reduce risks early in the life-course. We describe a mixed methods formative study of health professional’s perspectives of antenatal and post-partum diabetes screening and management, including enablers and barriers to care. Methods Health professionals involved in providing diabetes care in pregnancy, from a range of health services across the Northern Territory, completed the survey (n = 82) and/or took part in interviews and/or focus groups (n = 62). Results Qualitative findings highlighted factors influencing the delivery of care as reported by health professionals, including: whose responsibility it is, access to care, the baby is the focus and pre-conception care. The main challenges were related to: disjointed systems and confusion around whose role it is to provide follow-up care beyond six weeks post-partum. Quantitative findings indicated that the majority of health professionals reported confidence in their own skills to manage women in the antenatal period (62%, 40/79) and slightly lower rates of confidence in the postpartum interval (57%, 33/58). Conclusion These findings regarding whose role it is to provide postpartum care, along with opportunities to improve communication pathways and follow up care have informed the design of a complex health intervention to improve health systems and the provision of DIP related care.

A clinical decision report using: Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, Jurado J, Della Penna N, Celi LA. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest. 2021 Jan;159(1):108-111. https://doi.org/10.1016/j.chest.2020.06.082 for a patient hospitalized with COVID pneumonia requiring high flow oxygen.

High grade serous ovarian cancer (HGSOC) is a highly heterogeneous disease that often presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to measuring response to neoadjuvant chemotherapy (NACT) and understanding its determinants. Here we propose a radiogenomic framework integrating clinical, radiomic, and blood-based biomarkers to measure and predict the response of HGSOC patients to NACT, showing how quantitative imaging data can serve as the backbone of multi-scale data integration. We developed and validated our approach in two independent highly-annotated multi-omic multi-lesion data sets. In a discovery cohort (n=72) we found that different tumour sites present distinct response patterns, and identified volumetric response assessment as a better predictor of overall survival (OS) than RECIST 1.1 status. We trained an ensemble machine learning approach to predict tumour volume response to NACT from data obtained prior to treatment, and validated the model in an internal hold-out cohort (n=20) and an independent external patient cohort (n=42). Benchmarking integrated models against models built on single data types highlighted the importance of comprehensive patient characterisation. Our study sets the foundation for developing new clinical trials of NACT in HGSOC.

Background Young people living in remote Aboriginal communities experience some of the highest rates of chlamydia (CT) and gonorrhoea (NG) infection globally. A cluster-randomised controlled trial (TTANGO) in 11 remote primary health services demonstrated point-of-care (POC) testing for CT/NG was acceptable, accurate, improved the uptake and timeliness of treatment, and was cost-saving. Subsequently, POC testing was scaled-up and implemented in a further 20 remote health services (TTANGO2 program) across four jurisdictions (31 in total). We determine whether the uptake of POC testing observed in the trial was also achieved and sustained during the long-term program. Methods We conducted descriptive, interrupted time series and trajectory analyses to compare POC testing patterns over two time periods (trial: 2013–15 and program: 2016–19). For the trajectory analysis, we applied a Poisson model to identify and fit health services to testing groups. Results Among the 11 services who participated in both the trial and program, 7871 tests were conducted in total. The median number of tests per month in the trial was 241(IQR:178–305) and 408(IQR:294–538) in the program, with no significant trend in the trial (5.6 tests per month, p=0.190) but a significant increasing trend in the program (10.52 tests per month, p Conclusions Our findings suggest POC testing can be scaled-up and sustained as part of a routinely implemented program, achieving greater than expected testing numbers to support the clinical and public health benefits of more timely treatment. Further research is underway to investigate barriers among the ‘low’ testing sites. These findings support the proposed transition from syndromic management towards aetiological diagnosis and treatment in low- and middle-income countries.

Placental infection by SARS-CoV-2 with various pathologic alterations reported. Inflammatory findings, such as extensive perivillous fibrin deposition and intervillous histiocytosis, have been postulated as risk factors for fetal infection by SARS-CoV-2. We describe the placental findings in a case of a 31-year-old mother with SARS-CoV-2 infection who delivered a preterm female neonate who tested negative for SAR-CoV2 infection. Placental examination demonstrated a small for gestational age placenta with extensive intervillous histiocytosis, syncytiotrophoblast karyorrhexis, and diffuse intervillous fibrin deposition. Immunohistochemical staining demonstrated infection of the syncytiotrophoblasts by SARS-CoV-2 inversely related to the presence of intervillous histiocytes and fibrin deposition. Our case demonstrates that despite extensive placental pathology, no fetal transmission of SARS-CoV-2 occurred, as well as postulates a relationship between placental infection, inflammation, and fibrin deposition.

Background Renal impairment (RI) is a common complication of multiple myeloma (MM) and remains a poor prognostic factor despite improved survival with newer therapies. Patients and Methods We evaluated baseline characteristics, treatment, and outcomes of newly diagnosed MM patients with RI at diagnosis in the Australia and New Zealand Myeloma and Related Diseases Registry over 5 years to April 2018; we compared patients with RI (estimated glomerular filtration rate [eGFR] Results Overall, 36% of patients with newly diagnosed MM had RI; they were older, had more advanced disease and comorbidities, and worse performance status. Bortezomib-based induction therapy was most commonly used, although administered to fewer RI patients, despite similar response rates. Patients with RI were less likely to receive ASCT; however, recipients had longer progression-free survival (PFS) and overall survival (OS). Patients with RI had shorter OS and PFS after adjusting for age. In ASCT recipients with RI versus no RI, there was no difference in PFS and OS. Conclusion Our findings in “real world” MM patients with RI confirm that patient-, disease-, and treatment-related factors (such as suboptimal bortezomib and ASCT use), and delays in commencing therapy, might contribute to poorer outcomes, and support the use of ASCT in patients with RI.

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births37 weeks was not significant on multivariate analysis.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.摘要: 背景 在澳大利亚北部地区, 原住民母亲的婴儿出生率占33%, 她们妊娠期间出现高血糖的风险很高。原住民母亲在妊娠期间的2型糖尿病(T2D)患病率与非原住民澳大利亚母亲相比较要高10倍, 并且经常使用二甲双胍治疗。我们利用临床登记表数据评估了妊娠期间使用二甲双胍治疗与出生结果之间的关系。 方法 这项研究从2012至2016年纳入了妊娠糖尿病(gestational diabetes, GDM)、妊娠期新诊断糖尿病(newly diagnosed diabetes in pregnancy, DIP)以及既往已经存在T2D的妇女。对妊娠晚期使用二甲双胍的数据进行了分析。根据母亲年龄、体重指数、产次以及胰岛素使用情况校正了回归模型。 结果 在1649名孕妇中有814名(49.4%)为原住民妇女, 其中234名(28.7%)为T2D(非原住民妇女T2D比例为4.6%；P 0.001)。原住民妇女的二甲双胍使用率更高(在T2D中为84%-90%, 在GDM/DIP中为42%-48%), 并且在非原住民妇女中随着时间的推移使用率在上升(在T2D中为43%-100%, 在GDM/DIP中为14%-35%)。在合并GDM/DIP的原住民妇女中, 使用二甲双胍治疗组与不使用二甲双胍治疗组之间的剖宫产率(分别为51%与39%; 校正后的odds ratio [aOR]为1.25, 95%置信区间[CI]为0.87-1.81)、出现大胎龄率(分别为24%与13%；aOR为1.5, 95% CI为0.9-2.5)、新生儿出现严重不良事件率(分别为9.4%与5.9%；aOR为1.32, 95% CI为0.68-2.57)都没有显著性差异。使用二甲双胍治疗与胎龄更小(分别为37.7与38.5周)独立相关, 但是将单独接受药物营养治疗的妇女排除之后, 这种风险没有独立地处于较高的水平, 并且多变量分析显示37周的出生率并没有显著地升高。 结论 我们没有发现任何与妊娠期间高血糖妇女使用二甲双胍治疗出现不良结果相关的明确证据。.

Introduction Multiple myeloma (MM) is an incurable blood cancer with a high disease burden. Early assessment of health-related quality of life (HRQOL) can help to guide therapy planning. EQ-5D-5L (EQ5D) scores are collected in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) at diagnosis and follow-up as a non-mandatory item. We describe the use of EQ5D utility scores to assess patients’ HRQOL at diagnosis. Methods Utility scores are a measure of HRQOL, from ‘0’ (equal to death) to ‘1’ (full health). Scores were calculated for Australian patients with EQ5D data at diagnosis on the MRDR (Feb 2013 - Mar 2021) using a scoring algorithm developed for Australia1. Kaplan-Meier methods were used for survival analysis. Results Of 2239 Australian patients with MM on the MRDR, 483 had baseline EQ5D within 6m of diagnosis, with data for all 5 dimensions. Median age was 68y (59-76), 63% were male, and median overall survival was 63.0m (54.1-NR). In self-care, 66% of pts reported no problems at diagnosis, while only 22% were pain-free. Problems with mobility were reported in 55%, anxiety/depression in 56%, and problems with usual activities in 67% of patients at diagnosis. Patient characteristics were compared between EQ5D utility score groups (Q1: Conclusion Pain/discomfort was the most frequently reported health issue in MM, and self-care related problems the least, compared to the other health dimensions. EQ5D utility scores in Australian MRDR patients with MM were independent of age, gender and disease stage (ISS=3), but high scores were associated with higher EQ VAS score, improved ECOG, less cardiac disease, and better overall survival. HRQOL of MM patients at diagnosis has prognostic potential with better EQ5D utility scores associated with longer overall survival

Background: In Australia’s Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)]. Methods: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48%Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy(DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancywas also recruited. Results: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP,Indigenous women demonstrated poorer birth outcomes than non-Indigenous women:large for gestational age, 19 vs 11%, p ¼ 0002; neonatal fat 11.3 vs 10.2%, p < 0.001. Inthe full cohort, on multivariate regression, T2DM and DIP were independently associated(and Indigenous ethnicity was not) with pregnancy outcomes Conclusions: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia.As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring. Refereed/Peer-reviewed

Background: Fluid therapy is a ubiquitous part of management of critically ill patients with traumatic brain injury (TBI) and may impact on outcome. Our aim was to quantify variability in current fluid therapy in patients with TBI admitted at European and Australian Intensive Care Units (ICUs) and to study the association between fluid therapy and outcome after TBI. Methods: We analyzed data from patients admitted to the ICU with TBI and aged 16 and older included in the observational European CENTER-TBI and Australian OzENTER-TBI studies. The association of net daily fluid balance and -input with outcome (ICU mortality and functional outcome at 6 months) was analyzed at patient level with mixed effects logistic and ordinal regression with a random intercept for centre and adjustment for patient characteristics, and at centre level with centre as instrumental variable. Findings: In total, 2125 patients were included (1005 patients with isolated TBI). Mean daily fluid input ranged from 1·5 to 4·2L per centre. More positive daily mean fluid balance and fluid input were associated with worse outcome in patient-level analyses (fluid balance: ORs per 0·1L increase 1·10 [95%CI:1·07–1·13] and 1·03 [95%CI:1·02–1·05] for ICU mortality and functional outcome respectively; fluid input: ORs 1·05 [95%CI:1·03–1·06] and 1·03 [95%CI:1·02–1·04]). Centre-level analysis showed similar associations for fluid balance (ORs 1·15 [95%CI:1·02-1·29]; and 1·07 [95%CI:1·01-1·12], but not for fluid input (ORs: 0·95 [95%CI: 0·90-1·00]; and 1·01 [95%CI:0·99–1·03]). Interpretation: In critically ill patients with TBI, there is significant variability in fluid management with more positive fluid balances being associated with worse outcomes. Further research is needed to establish whether mitigation of positive fluid balance by less liberal fluid administration contributes to improved outcome. Funding: This research was funded by the European Commission 7th Framework program (602150) and the Australian Health and Medical Research Council (NHMRC 1074181). Declaration of Interests: DJC is an Australian NHMRC Practitioner Fellow and reports grants from the NHMRC and consulting fees to Monash University from PresSura Neuro. AIM declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. DKM reports grants from the UK National Institute for Health Research, during the conduct of the study; grants, personal fees, and non-financial support from GlaxoSmithKline; personal fees from Neurotrauma Sciences, Lantmaanen AB, Pressura, and Pfizer, outside of the submitted work. ES reports personal fees from Springer, during the conduct of the study. All other authors declare no competing interests. Ethics Approval Statement: In each recruiting site ethical approval was given.

Background The most immediate response of the research community to COVID-19 has been a focus on understanding the effects, treatment and prevention of infection. Of equal and ongoing importance is elucidating the impact of mitigation measures, such as lockdown, on the well-being of societies. Research about mental health and lockdown in the UK has predominately involved large surveys that are likely to encounter self-selection bias. Further, self-reporting does not constitute a clinical judgement. Aims To (a) compare the age, gender and ethnicity of patients experiencing mental health emergencies prior compared with during lockdown, (b) determine whether the nature of mental health emergencies has changed during compared with before lockdown, (c) explore the utility of emergency medical service data for identifying vulnerability to mental health emergencies in real time during a pandemic. Method A total of 32 401 clinical records of ambulance paramedics attending mental health emergencies in the East Midlands of the UK between 23 March and 31 July 2020 and the same period in 2019 were analysed using binary logistic regression. Results People of younger age, male gender and South Asian and Black ethnicity are particularly vulnerable to acute mental health conditions during lockdown. Patients with acute cases of anxiety have increased during lockdown whereas suicide and intentional drug overdose have decreased. Conclusions Self-reported data may underrepresent the true impact of lockdown on male mental health and ethnic minority groups. Emergency medical data can be used to identify vulnerable communities in the context of the extraordinary circumstances surrounding the current pandemic, as well as under more ordinary circumstances.

Aboriginal and Torres Strait Islander women have high rates of gestational diabetes (GDM). The Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study is a prospective longitudinal cohort of women with type 2 diabetes (T2D), GDM or normoglycemia in pregnancy in the Northern Territory, Australia. In this analysis we report progression to prediabetes and T2D at 2.5 years [range 2.1, 3] postpartum in a subgroup of Aboriginal and Europid women with GDM and normoglycemia in pregnancy (n=337). Women with pre-existing T2D were excluded. Data were analysed using Fisher’s exact tests. Among Aboriginal women with GDM we assessed predictions for progression using multivariate logistic regression. Aboriginal women with GDM (n=111) were younger than Europid women with GDM (n=104) (29 years (SD 5.9) vs. 32 (5.6) p Disclosure A. Wood: None. J. Boyle: None. F. Barzi: None. E.L. Barr: None. M.J.I. Hare: None. A. Titmuss: None. E. Death: None. M. Kirkwood: None. A. Simmonds: None. E.M. Moore: None. J. Oats: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. P.Z. Zimmet: None. A.D. Brown: None. J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. L.J. Maple-Brown: None.

Background Receiving a breast cancer diagnosis can be traumatic and anxiety-producing. The way the diagnosis is disclosed to patients can affect their experience. Objectives The aim of this article is to determine patient preferences for being informed of a breast cancer diagnosis and the breast nurse navigator (BNN) role during the diagnostic experience. Methods A survey was mailed to 517 patients with breast cancer. Summary statistics were performed on 199 completed surveys. Findings Patients preferred to hear their diagnosis in person. BNNs were more likely to provide the right amount of support and resources compared to other providers. Patients described the following preferences.

Methicillin-resistant Staphylococcus aureus (MRSA) in prisons can result in serious morbidity and death. We reviewed rates and risk factors for MRSA infection in custody, searching Medline, EMBASE, and CINAHL databases. Between 1997 and 2015, 17 studies reported MRSA skin and soft tissue infections (SSTIs), with four case reports of MRSA non-SSTI (necrotizing pneumonias, brain abscess, and epiduritis). Significant associations with MRSA SSTI were found: MRSA colonization, previous skin infection, sharing soap or personal items, SSTI presenting as an abscess or furuncle, younger age, non-Caucasian, overweight, communal laundering, infrequent handwashing, lower hygiene score.early identification, isolation, and treatment of skin infections at admission; education on maintaining skin integrity and presenting early with skin infections; increasing hygiene by not sharing items and encouraging handwashing; improved handling and disinfection of communal laundering; influenza vaccination for all prisoners and staff; and population-based longitudinal studies including younger detainees.

Introduction Serious infection is common in patients with multiple myeloma (MM), and associated with major morbidity and mortality. Immunoglobulin (Ig) replacement is frequently used to reduce frequency and severity of infections, however evidence is based on small trials conducted >20 years ago. Ig utilisation and associated costs in this patient cohort are rising worldwide. In Australia (Aus), Ig for secondary hypogammaglobulinaemia is funded if total IgG is below lower limit of reference range with a history of recurrent or severe bacterial infection, or in severe hypogammaglobulinaemia (IgG < 4 g/L excluding paraprotein). In New Zealand (NZ), patients generally require a history of recurrent infections and trial of oral antibiotics before commencing Ig. This study aims to outline Ig use in the "real-world" MM setting, identify variation in and predictors of use, and describe association of Ig with survival outcomes. Methods Retrospective review of patients registered on the MRDR, a prospective registry established in 2012, currently open at >60 sites across Aus/NZ. Patients with a diagnosis of MM or plasma cell leukaemia with verifiable data regarding Ig use were included in this analysis. Ig use was confirmed using medical/laboratory records, national Aus Ig dispensing tool or the NZ Blood Service portal. Quality of survival outcomes and cause of death data was augmented via linkage with national death registries. Baseline patient/disease characteristics, therapy and survival outcomes were compared between patients who received any Ig within 24 months of MM diagnosis and non-recipients using chi-square tests for categorical variables and rank sum tests for continuous variables. Variation in Ig use across sites were compared. Kaplan-Meier survival analysis was used to estimate time to Ig and duration of use. A time-dependent Cox analysis was used to compare survival for patients whilst on and off Ig therapy. All statistical analysis was completed on STATA/IC statistical software v16.1 (College Station, TX, USA). Results As of July 2021, >4600 patients with plasma cell dyscrasias are registered on the MRDR. Of these, 2025 patients from 13 sites (12 Aus across five states/territories and one NZ) with verifiable data on Ig were included. 242 (12.0%) received Ig during follow-up, with a median time from MM diagnosis to Ig use of 14.2 months, median duration of Ig use of 54.9 months, and median patient follow-up time of 23 months (Figure 1). At 24 months following MM diagnosis, 14.9% (160 of 1075 patients reaching 24-month follow up) received Ig, and a further 7.6% (82 patients) received Ig later, after 24 months. Administration of Ig within 24 months post-MM diagnosis varied widely across Aus states and territories (2.7%-29.6%), and was 2.0% from one NZ site. Patients administered Ig within 24 months post-MM diagnosis had lower baseline IgG (3.7 vs. 5.6 g/L, p Ig use was not associated with an overall survival benefit (HR=0.79, 0.50-1.24, p=0.3). At time of last follow-up, there were 577 deaths (28.5%). Available data on cause of death was available for 175 deaths (30.3%). Of these, 65 deaths (37.1%) had infection listed as primary/secondary cause of death (COD). 64 of 65 infection-related deaths occurred in non-Ig recipients. In patients who received Ig (at any time), 12.5% had infection as primary/secondary COD, compared to 38.5% in non-recipients (p=0.14). Conclusion This Aus/NZ analysis found that 14.9% of MM patients received Ig by 24 months post-MM diagnosis with wide variation in practice. Ig use was associated with lower baseline Ig levels (all subtypes), abnormal FISH and first-line IMiD/anti-CD38 therapy. In this "real-world" cohort, Ig use was not associated with survival, highlighting the need for well-designed contemporary studies to inform evidence-based patient selection, especially with increasing use of Ig and targeted anti-myeloma therapies, and a high burden of infection-related mortality. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Harrison: Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene/ Juno/ BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusa: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Honoraria. Mollee: Janssen, Pfizer: Research Funding; Amgen, BMS, Janssen, Caelum, EUSA, Pfizer, SkylineDx, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: No personal fees received. Quach: GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Spencer: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Wood: Amgen, Celgene, Gilead, Janssen, Novartis, Sanofi, Takeda: Research Funding; Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda.: Other: The Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) has received funding from Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda. . McQuilten: Amgen, Celgene, Gilead, Janssen, Novartis, Sanofi, Takeda: Research Funding; Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda.: Other: The Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) has received funding from Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda. .

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. Results: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications. Refereed/Peer-reviewed

Background In addition to 4 CRAB criteria, 3 biomarkers were adopted as myeloma-defining events: clonal marrow plasma cell (PC) percentage ≥60%, serum free light chain ratio (SFLCR) ≥100 and >1 MRI focal lesion, known as SLiM (SixtyLightchainMRI), but there has been no analysis of their clinical impact. Methods We compared the characteristics, treatment & outcomes of 1686 pts diagnosed by CRAB and 132 pts by SLiM enrolled in the MRDR from 2013 - 2018, to assess the impact of these criteria on clinical practice and treatment outcomes. Results Patient & Disease characteristics. In 132 SLiM pts, 48 had SFLCR≥100, 58 BMPC>60% and 26 were known to have both, nil had MRI lesions (limited by MRI availability). CRAB pts included a higher proportion with advanced stage ISS-3 (35.6% v 10.7%, p Outcomes OS was longer in SLiM than CRAB (median 76.3 v 65.2 m, p=0.02, HR 1.75), with no difference in PFS (30.8 v 30.2 m, p=0.30, HR 1.17). However PFS2 was superior for SLiM of 48.7 m v 38.2 m for CRAB (HR 1.38, p=0.06). No difference in best response rates (≥PR & ≥VGPR) was seen in SLiM v CRAB. Within SLiM, comparing 3 groups: those who satisfied the criteria of SFLCR>100 only (SFLC group, n=28), PC≥60% only (PC group, n=34) or both (n=20), pts with Discussion We found differences in characteristics between SLiM and CRAB pts – higher BM PC infiltration and SFLCR in SLiM, and a trend for higher incidence of FISH anomalies in CRAB. SLiM pts had a median OS 11.1 m longer than CRAB, but no difference in PFS1 or response rates. The OS difference of -1 yr could reflect the earlier initiation of therapy in SLiM. However the trend for a longer PFS2 for SLiM indicates improved treatment outcome to therapy at first relapse, suggesting the shorter PFS2 of CRAB pts may result from residual or re-emerging drug-resistant clones. Conclusions In a real-life population our findings support the benefit of earlier initiation of therapy by SLiM criteria, with an improved OS and a trend towards improved outcome at first relapse (PFS2). Patients with PC criteria in the SLiM cohort have an increased risk for suboptimal response compared to those who satisfy SFLC criteria alone.

Background and Aims: The Asia-Pacific (APAC) Myeloma and Related Diseases Registry (MRDR) collects data on epidemiology, treatment and outcome trends for patients with multiple myeloma (MM) in participating regional countries. Prevalence of MM is expected to continue to increase with ageing populations and improvements in survival. Although some MM data are available for Asia, very few exist at regional level. Generation of 'real world evidence' on practice and outcomes is important to complement data from clinical trials. In the APAC MRDR, regional clinical experts provide local clinical context and registry oversight, and participating hospitals obtain local ethics approval and manage patient recruitment and data collection. Methods: The APAC MRDR prospectively collects observational data on patient characteristics, diagnosis, medical history, treatment (including supportive therapies), and outcomes (overall and progression-free survival, and quality of life using the EQ-5D-5L) on newly diagnosed MM (NDMM), plasma cell leukaemia, plasmacytoma, and MGUS patients via a secure, country-specific, web-based database. Participants are reviewed 4-monthly for a minimum of 2 years. Preliminary data from October 2018 to June 2020 were analysed. Results: 20 hospitals have ethics approval to participate and patient recruitment has commenced at 14 hospitals in Korea, Singapore, and Malaysia. Sites in Taiwan will also start recruitment in 2020, and sites in China have been identified. To date, a total of 469 patients (419 NDMM) have been enrolled, of which, data from 348 (83%) NDMM participants from Korea, Singapore, and Malaysia were available for analysis. Results are presented in Table 1. Summary and Conclusions: The APAC MRDR is now successfully established and expanding. As data mature, these will provide important new information on the epidemiology and treatment of MM across the APAC region, and provide opportunities for regional benchmarking and collaborative research. Disclosures Spencer: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Secura Bio: Consultancy, Honoraria; Pharmamar: Research Funding; Roche: Honoraria; Servier: Consultancy, Honoraria, Research Funding; HaemaLogiX: Consultancy, Honoraria, Research Funding.

Background Acute exacerbation of COPD (AECOPD) has a significant impact on health-care use, including physician visits and hospitalizations. Previous studies and reviews have shown that pulmonary rehabilitation (PR) has many benefits, but the effect on hospitalizations for AECOPD is inconclusive. Methods A literature search was carried out to find studies that might help determine, using a meta-analysis, the impact of PR on AECOPD, defined as unscheduled or emergency hospitalizations and ED visits. Cohort studies and randomized controlled trials (RCTs) reporting hospitalizations for AECOPD as an outcome were included. Meta-analyses compared hospitalization rates between eligible PR recipients and nonrecipients before and after rehabilitation. Results Eighteen studies were included in the meta-analysis. Results from 10 RCTs showed that the control groups had a higher overall rate of hospitalization than did the PR groups (control groups: 0.97 hospitalizations/patient-year; 95% CI, 0.67-1.40; PR groups: 0.62 hospitalizations/patient-year; 95% CI, 0.33-1.16). Five studies compared admission numbers in the 12 months before and after rehabilitation, finding a significantly higher admission rate before compared with after (before: 1.24 hospitalizations/patient-year; 95% CI, 0.66-2.34; after: 0.47 hospitalizations/patient-year; 95% CI, 0.28-0.79). The pooled result of three cohort studies found that the reference group had a lower admission rate compared with the PR group (0.18 hospitalizations/patient-year; 95% CI, 0.11-0.32 for reference group vs 0.28 hospitalizations/patient-year; 95% CI, 0.25-0.32 for the PR group). Conclusions Although results from RCTs suggested that PR reduces subsequent admissions, pooled results from the cohort studies did not, likely reflecting the heterogeneous nature of individuals included in observational research and the varying standard of PR programs.

p53 has been implicated in the pathogenesis of obesity and diabetes, in part, by regulating whole body energy homeostasis. Conflicting evidence from mice with global alterations in p53 expression suggests the effects of p53 on metabolism are tissue-specific. Despite the critical metabolic role of the hepatocyte, the role of hepatocyte p53 is undefined. Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of type 2 diabetes remission and improves energy homeostasis at the cellular level. To define the role of hepatocyte p53 in metabolic regulation and the impact of VSG in this context, we performed VSG or sham (S) surgery in high fat diet-fed male hepatocyte-specific p53 knockout (KO) and wild type (WT) mice (n=9-12). Sham-operated mice were fed ad libitum (S-AL) or food restricted to match their body weight to VSG-operated mice (S-WM). Body weight, food intake, adiposity, energy expenditure, and oral glucose tolerance were measured. Hepatocyte p53 ablation increased body weight which was corrected by food restriction and VSG (final weight (g): S-AL-WT=33±1, S-WM-WT=27±1, VSG-WT=29±1, S-AL-KO=38±1, S-WM-KO=28±1, VSG-KO=28±1, P Disclosure M.M. Holter: None. D. Garibay: None. A.K. McGavigan: None. L. Nguyen: None. E. Moore: None. E. Daugherity: None. P. Cohen: None. K.M. Kelly: None. R. Weiss: None. B. Cummings: None. Funding Cornell University; National Cancer Institute (R21CA195002)

Background Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO). Methods Pre-planned analysis of patients included in the EPO-TBI (ClinicalTrials.gov NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI. Results Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 [10%] with KDIGO 1, 11 [2%] patients with KDIGO 2, and 11 [2%] patients with KDIGO 3). Male gender (hazard ratio [HR] 4.0 95% confidence interval [CI] 1.4-11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1-1.4, P

Objective: Given the paucity of research among prisoners, this study aimed to examine the prevalence and psychiatric comorbidity associated with adult ADHD. Method: The study was conducted at four NSW correctional facilities (2 male; 2 female). Results: Thirty-five percent of the sample screened positive for adult ADHD, and 17% of the sample met criteria for a full diagnosis. After adjustment, benzodiazepine dependence, borderline personality disorder, social phobia, antisocial personality disorder, and a number of lifetime psychological disorders remained significantly and independently associated with the diagnosis of adult ADHD. Lowering the threshold on the ADHD Self-Rating Scale to ≥3 (vs. ≥4) increased the sensitivity (80%-93%), but lowered the specificity (55%-47%). Conclusion: Adult ADHD among NSW prisoners is elevated, with substance use disorders and psychiatric comorbidity common. A greater acceptance of this disorder among prisoners, and appropriate treatment, is warranted.

Available literature on the detection of transferred DNA does not address the interpretation issues in relation to who wore rather than touched the garment. To acquire a greater knowledge of the rate of detectable wearer, toucher and background DNA, 63 males wore their own underpants for 12h. The inside-waistband was handled by one of 11 female volunteers for 15s. The waist-band was mini-taped and subjected to DNA profiling with the AMPFlSTR(®) NGM SElect™ kit. The findings show that on worn garments the probability of observing reportable DNA profiles is 61.9%. The wearer was detected as a single profile or part of a mixed profile in 50.8% of samples. When the wearer was present in a mixture, he was always observed as the major contributor. The toucher was detected on 11.1% of underpants. Reportable background DNA (non-wearer and non-toucher) occurs in 14.3% of samples and may affect the assessment of who wore the garment. Greater knowledge of the frequency of detection of reportable wearer DNA and/or toucher allows scientists to evaluate the likelihood of observing a matching profile if an individual wore a garment rather than touched it in disputed case scenarios.

Introduction: Recent studies suggest that incidence of multiple myeloma (MM) is increasing in Asian countries. Prevalence is also expected to rise due to ageing populations and advances in treatment. Therapeutic options continue to expand as new, targeted agents enter the market. However, despite advances in therapy and supportive care, MM remains incurable. Most patients receive care outside the setting of clinical trials. Therefore, the generation of Real-World Evidence (RWE) on practice, including long-term monitoring and evaluation of current and future treatment strategies, is important in informing optimal therapies for MM and enable benchmarking to improve outcomes, quality of life (QoL), and cost-effectiveness of care for patients. Some country-specific data are available in Asia, but few at regional level. We established the Asia-Pacific (APAC) Myeloma and Related Diseases Registry (MRDR) in 2018, as a regional collaboration and sister registry to the Australian and New Zealand MRDR (ACTRN12618000659202). The aims are collection of a standardised APAC dataset for analysis and benchmarking. Key opinion leaders from the participating countries were invited to form the steering committee to provide local clinical context and oversight of the registry. Early in the process, ethics committees and legal counsel were consulted to assist with challenges presented by the diversity in data privacy and ethical regulations across the APAC region. Participating hospitals are responsible for obtaining local ethics approval, patient recruitment, and data collection. Participants provide written informed consent before data collection. Methods: The APAC MRDR prospectively collects observational data on patient characteristics, diagnosis, medical history, treatment (including supportive therapies), and outcomes (overall and progression-free survival, and QoL using the EQ-5D-5L) on newly diagnosed MM (NDMM), plasma cell leukaemia, plasmacytoma, and MGUS patients via a secure, country-specific web-based database. Whilst the core dataset is standardised across countries to ensure comparability, regional differences such as units of measurements and local privacy laws were accommodated in the design of each country's database. Participants are reviewed 4-monthly for a minimum of 2 years. Longer-term outcomes will be collected through linkage with local cancer and death registries. Six-monthly hospital reports, providing de-identified, risk-adjusted outcome data at hospital- and country-level, will be provided to contributing hospitals. Preliminary APAC MRDR data from October 2018 to June 2019 were analysed. Results: Eleven hospitals now have Institutional Review Board approval to participate and patient recruitment has commenced at 6 hospitals in Korea and Singapore. Sites in Taiwan, Hong Kong, China, and Malaysia are in progress. To date, 182 patients have been enrolled and data collection on these patients is in progress. At the time of analysis, 85% (96/113) were NDMM. Median age was 66 years (IQR: 59-73) and 54% were male. Median EQ5D VAS Health State score at diagnosis was 70 (IQR: 50-80; self-report: 100=best health imaginable, 0=the worst). Comorbidities were present in 47%. Proportion of patients with main paraprotein type IgG: 64%, IgA: 17%, light chain only Kappa: 13%, light chain only Lambda: 6%. Median number of days from diagnosis to chemotherapy was 9.5 (IQR: 3-15). The top two most frequently used first-line regimens for NDMM patients in Korea and Singapore were: Korea: 1. bortezomib/thalidomide/dexamethasone (VTd: 39%), 2. lenalidomide/dexamethasone (Rd: 27%), and Singapore: 1. VTd: 41%, 2. bortezomib/cyclophosphamide/dexamethasone (VCD): 25%. Overall response rate to first-line chemotherapy (≥PR) was 86% (44/51). Conclusion: The APAC MRDR database is expanding and, as data mature and feedback is provided to participating sites, will provide RWE that will contribute to our understanding on current myeloma treatment strategies and patient outcomes in the Asia-Pacific region. Future plans include expansion to additional sites and countries, and linkage with local cancer and death registries. The registry can also serve as a regional resource by providing infrastructure and identifying eligible participants for clinical trials and other research. Disclosures Aoki: Janssen Asia-Pacific: Research Funding. Moore:Takeda: Research Funding; Gilead: Research Funding. Wood:Bristol-Myers Squibb: Research Funding; Novartis: Research Funding; Alexion: Research Funding; Roche: Research Funding; Takeda: Research Funding; Gilead: Research Funding; Janssen-Cilag: Research Funding; Amgen: Research Funding; CSL Behring: Research Funding; Sanofi: Research Funding; Celgene: Research Funding; Abbvie: Research Funding. McQuilten:Gilead Sciences: Research Funding; CSL Biotherapies: Research Funding; Celgene: Research Funding; AbbVie: Research Funding; Takeda Pharmaceuticals: Research Funding; Janssen-Cilag: Research Funding. Spencer:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Specialised Therapeutics Australia: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background: The paradigm for treatment selection in newly diagnosed (ND) multiple myeloma (MM) is largely predicated on establishment of suitability for front-line autologous stem cell transplantation. In this context, real-world evidence from multiple jurisdictions demonstrates that the most widely employed front-line (1L) therapies are bortezomib (B)-based triplets in transplant-eligible patients, and in transplant-ineligible patients, B-based triplets (or doublets) or the combination of lenalidomide and dexamethasone. While a sound hypothetical rationale for treatment stratification at diagnosis is recognised, viz alternative treatments for high-risk (HR) versus standard-risk disease, this is rarely employed in either everyday practice or clinical trials. A significant impediment to such an approach is the lack of a uniformly recognised risk stratification model that not only recognises truly HR disease (e.g. median survival from diagnosis < 24 months [m]) but is also accessible and affordable. Against this background we evaluated data from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) to define characteristics of 'functional' HR disease that could inform response-adaptive strategies, thus enabling the appropriate therapeutic targeting of HR patients. Methods: NDMM patients enrolled on to the MRDR since February 2013 with available data were evaluated. Patients were defined as either sub-optimal responders (SOR) to 1L if their best response was minimal response or stable disease (but not progressive disease [PD]), or early progressors (EP) if they demonstrated PD within 12m of commencing 1L therapy, irrespective of whether this occurred on or after the completion of 1L therapy. For categorical variables p-values were determined using a Pearson's chi-squared test, for continuous variables p-values were calculated using a Wilcoxon rank-sum test. Survival analysis was performed using the Kaplan-Meier method and p-values determined with the log-rank test. Results: 1320 NDMM patients were included with a median follow-up of 23m (12-37 IQR, 0-83 range). Of these, 152 were SOR (11.5%) and 118 were EP (8.9%). At diagnosis only 2 factors associated with SOR were identified: age >70y (p70y OR 1.59 (95% CI 1.11-2.28; p=0.01) and B-based 1L OR 0.47 (95% CI 0.29-0.75; p=0.001). Median overall (OS) survival for SOR was similar to that of responders (R): 57.8m (95%CI, 36.7 - NR) vs 59.3m (95%CI, 55.4 - NR), for SOR vs R, respectively, but with an excess of early deaths from the time of diagnosis in a sub-set of SOR patients: survival at 12m 85% vs 96%, 24m 73% vs 88% and 36m 61% vs 79%, for SOR vs R, respectively, (HR 1.6, 95% CI 1.2 - 2.3; p=0.001) (Figure A). Conversely, EP was associated with a range of indicators of higher-disease burden: higher ISS (p Conclusions: These real-world data demonstrate that 40% of patients with SOR will die within 3y of diagnosis. More strikingly, EP is associated with high disease burden at diagnosis and high likelihood of refractoriness at 1R, with median OS of only 20.2m. While recent data demonstrate that 1L triplets or quadruplets containing the monoclonal antibody daratumumab may mitigate against both SOR and EP, these approaches remain financially implausible in most jurisdictions. A more affordable approach could be informed by response-adaptive trials in functional HR MM in an attempt to address the ongoing unmet therapeutic need in these patient groups. Figure Disclosures Spencer: Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics Australia: Consultancy, Honoraria; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mollee:Janssen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Blacklock:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Harrison:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: investigator on studies, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Quach:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ho:Celgene: Other: investigator meeting travel costs; Janssen: Other: investigator meeting travel costs; Novartis: Other: investigator meeting travel costs; La Jolla: Other: investigator meeting travel costs. Spearing:Celgene: Consultancy, Honoraria, Other: Travel costs; Roche: Other: Travel costs. Prince:Amgen: Consultancy, Honoraria; Celgene: Honoraria; Takeda: Consultancy, Honoraria; Allergan: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Moore:Gilead: Research Funding; Takeda: Research Funding. McQuilten:Takeda Pharmaceuticals: Research Funding; AbbVie: Research Funding; Janssen-Cilag: Research Funding; Celgene: Research Funding; Gilead Sciences: Research Funding; CSL Biotherapies: Research Funding. Wood:Roche: Research Funding; Gilead: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Janssen-Cilag: Research Funding; Novartis: Research Funding; Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding; Alexion: Research Funding; Celgene: Research Funding; CSL Behring: Research Funding.

OBJECTIVE: To assess the association of reported smoking cessation at various time points during pregnancy with fetal growth restriction. METHODS: This was a population-based retrospective cohort study of singleton nonanomalous live births using Ohio birth certificates, 2006–2012. Outcomes of women who reported smoking only in the 3 months before conception and women who reported smoking through the first, second, or third trimester were compared with a referent group of nonsmokers. Multivariate logistic regression assessed the association between smoking cessation at various times in pregnancy and fetal growth restriction less than the 10th and 5th percentiles. RESULTS: Of 927,424 births analyzed, 75% of mothers did not smoke. Of smokers, 24% smoked preconception only, 10% quit after the first trimester, 4% quit after the second trimester, and 59% smoked throughout pregnancy. The rate of fetal growth restriction less than the 10th and 5th percentiles among nonsmokers was 8.1% and 3.6%, respectively. Although smoking only in the preconception period did not significantly increase fetal growth restriction risk, smoking in any trimester did. The adjusted odds ratio (95% confidence interval) for fetal growth restriction less than the 10th and 5th percentiles, respectively, of cessation after the first trimester was 1.19 (1.13–1.24) and 1.25 (1.17–1.33) and 1.67 (1.57–1.78) and 1.83 (1.68, 1.99) for cessation after the second trimester. Women who reported smoking throughout pregnancy had the highest risks of fetal growth restriction, 2.26 (2.22–2.31) and 2.44 (2.37–2.51), after accounting for the influence of race, low socioeconomic status, and medical comorbidities. CONCLUSION: Smoking of any duration during pregnancy is associated with an increased risk of fetal growth restriction with decreasing risk the earlier that cessation occurs. Smoking cessation programs should focus on the benefit of quitting as early in pregnancy as possible. LEVEL OF EVIDENCE: II

Aim To describe the prevalence and risk factors for markers of poor oral health in Aboriginal and non-Aboriginal young people in custody in Australia. Methods All incarcerated youth, aged 13–21 years, in New South Wales Juvenile Custodial Centres between August and October 2009 were invited to participate and undertake a dental exam. The main outcome measures were an assessment of moderate/abundant plaque, periodontal disease, dental caries experience, mean decayed and/or filled and/or missing teeth (DMFT) index and untreated decay. Results Two hundred ninety-four participants (91% male, 46% Aboriginal) underwent a dental exam. Markers of poor oral health were common – 49.4% with moderate/abundant plaque, 34.4% with periodontal disease, mean DMFT 3.56 and 54% having untreated decay. Risk factors independently associated with poor oral health were geographical remoteness and non-fluoridation of the water supply of the usual residence, a shorter incarceration time and dental treatment outside of custody. Conclusions Young people entering custody have poor oral health, with those from geographically remote areas without water fluoridation at highest risk. The incarceration period is an opportunity for oral health improvements in these young people through access to dental treatment services. Better triaging systems are needed to identify those of greatest priority, and prevention services are needed.

Background: Environmental exposures play a role in COPD exacerbations. Developments in portable environmental sensors mean that patients can now carry a personal monitor (PAM) as they go about their lives to capture a direct link between individual activities, environmental exposures and their health. We developed a method of predicting exacerbations utilising long-term deployment of PAMs to improve disease management in COPD patients. Methods: 102 participants have been recruited. COPD patients are given a PAM to carry for up to six months, while keeping a symptoms diary and performing daily peak flow (PF). The PAM continuously records a range of parameters including location, tri-axial acceleration, temperature, noise, gaseous and particulate pollutants. Statistical algorithms allow automated assignment of pollutant dose and activity type, e.g. sleeping, cooking, smoking and transport mode, at high time resolution. Results: Initial statistical analysis found no overall association between environmental exposures and symptoms (e.g., PM2.5 vs PF, r=-0.02). However, significant associations were found between mean daily exposure and symptoms in some subjects (e.g., Participant 35 – nitric oxide vs PF: r=0.54**, PM2.5 vs PF: r=0.34**), suggesting highly variable susceptibility between individuals. More detailed potential associations, including lag, shape, duration and frequency of exposure, are currently being investigated. Conclusion: Identification of individualised susceptibility to environmental exposures will allow us to provide patients with personalised advice to alter their behaviour and decrease risk of exacerbation.

Background Aboriginal and Torres Strait Islander Australians experience a greater burden of disease compared to non-Indigenous Australians. Around one-fifth of the health disparity is caused by cardiovascular disease (CVD). Despite the importance of absolute cardiovascular risk assessment (CVRA) as a screening and early intervention tool, few studies have reported its use within the Australian Indigenous primary health care (PHC) sector. This study utilizes data from a large-scale quality improvement program to examine variation in documented CVRA as a primary prevention strategy for individuals without prior CVD across four Australian jurisdictions. We also examine the proportion with elevated risk and follow-up actions recorded. Methods We undertook cross-sectional analysis of 2,052 client records from 97 PHC centers to assess CVRA in Indigenous adults aged ≥20 years with no recorded chronic disease diagnosis (2012–2014). Multilevel regression was used to quantify the variation in CVRA attributable to health center and client level factors. The main outcome measure was the proportion of eligible adults who had CVRA recorded. Secondary outcomes were the proportion of clients with elevated risk that had follow-up actions recorded. Results Approximately 23% (n = 478) of eligible clients had documented CVRA. Almost all assessments (99%) were conducted in the Northern Territory. Within this jurisdiction, there was wide variation between centers in the proportion of clients with documented CVRA (median 38%; range 0–86%). Regression analysis showed health center factors accounted for 48% of the variation. Centers with integrated clinical decision support systems were more likely to document CVRA (OR 21.1; 95% CI 5.4–82.4; p

Introduction Sepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions. Methods and analysis ASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018. Discussion This substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians. Trial registration number Pre-results, ACTRN12613000349741.

Background: Rates of diabetes in pregnancy are disproportionately higher among Aboriginal than non-Aboriginal women in Australia. Additional challenges are posed by the context of Aboriginal health including remoteness and disadvantage. A clinical register was established in 2011 to improve care coordination, and as an epidemiological and quality assurance tool. This paper presents results from a process evaluation identifying what worked well, persisting challenges and opportunities for improvement. Methods: Clinical register data were compared to the Northern Territory Midwives Data Collection. A cross-sectional survey of 113 health professionals across the region was also conducted in 2016 to assess use and value of the register; and five focus groups (49 healthcare professionals) documented improvements to models of care. Results: From January 2012 to December 2015, 1,410 women were referred to the register, 48% of whom were Aboriginal. In 2014, women on the register represented 75% of those on the Midwives Data Collection for Aboriginal women with gestational diabetes and 100% for Aboriginal women with pre-existing diabetes. Since commencement of the register, an 80% increase in reported prevalence of gestational diabetes among Aboriginal women in the Midwives Data Collection occurred (2011–2013), prior to adoption of new diagnostic criteria (2014). As most women met both diagnostic criteria (81% in 2012 and 74% in 2015) it is unlikely that the changes in criteria contributed to this increase. Over half (57%) of survey respondents reported improvement in knowledge of the epidemiology of diabetes in pregnancy since establishment of the register. However, only 32% of survey respondents thought that the register improved care-coordination. The need for improved integration and awareness to increase use was also highlighted. Conclusion: Although the register has not been reported to improve care coordination, it has contributed to increased reported prevalence of gestational diabetes among high risk Aboriginal women, in a routinely collected jurisdiction-wide pregnancy dataset. It has therefore contributed to an improved understanding of epidemiology and disease burden and may in future contribute to improved management and outcomes. Regions with similar challenges in context and high risk populations for diabetes in pregnancy may benefit from this experience of implementing a register. Refereed/Peer-reviewed

OBJECTIVE:: Despite being at high risk, little is known about traumatic brain injuries (TBIs) among incarcerated young people. This study aims to describe the prevalence of TBI among incarcerated young people and assess the association with mental health, substance use, and offending behaviors. SETTING:: The 2009 NSW Young People in Custody Health Survey was conducted in 9 juvenile detention centers. PARTICIPANTS:: A total of 361 young people agreed to participate, representing 80% of all incarcerated young people. MAIN MEASURES:: Young people were asked if they ever had a head injury where they became unconscious or "blacked-out." The survey used the Kiddie Schedule for Affective Disorders for Children to assess for psychiatric disorders, the Alcohol Use Disorder Identification Test, and the Severity of Dependence Scale to measure problematic substance use. RESULTS:: The sample comprised 88% man, 48% Aboriginal, with an average age of 17 years. One-third (32%) of young people reported ever experiencing a TBI, and 13% reported multiple TBIs. The majority (92%) of "most serious" TBIs were defined as mild, and the most common cause was an assault (62% woman, 34% man). Young people who reported a history of TBI (compared with those reporting no TBI) were significantly more likely to be diagnosed with a mental health disorder, psychological distress, a history of bullying, problematic substance use, participation in fights, and offending behaviors. Reporting multiple (>2) TBIs conferred a higher risk of psychological disorders and problematic substance use. CONCLUSIONS:: Incarcerated young people have high rates of TBI. Enhanced detection of TBI among incarcerated young people will assist clinicians in addressing the associated psychosocial sequelae. Language: en

Background Intellectual disability (ID) is known to be more common in incarcerated groups, especially incarcerated youth. Aboriginal young people have higher rates of ID, and make up half of all youth in juvenile custody in New South Wales (NSW), Australia. We aimed to describe the prevalence of possible ID and borderline intellectual functioning (BIF) in young people in NSW custody, and to describe the association between possible ID and Aboriginality after adjusting for the inequalities in social disadvantage. Methods Baseline study of all youth in NSW Custodial Centres between August and October 2009, with 18-month follow-up. Using Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) and Wechsler Adult Intelligence Scale – Fourth Edition (WAIS-IV) cognitive assessments, possible ID was defined as Extremely Low Intellectual Quotient range (Full Scale Intellectual Quotient, FSIQ

Young offenders have a high prevalence of mental illness and a large proportion report experiencing a number of traumatic events during childhood, but there is little research exploring this association. This study describes the prevalence of, and association between, child maltreatment and post-traumatic stress disorder (PTSD) among young offenders. The study uses data collected as part of the 2009 NSW Young People in Custody Health Survey which was conducted in nine juvenile detention centers. This paper reports on findings from the baseline questionnaires and 18-months of re-offending data. The analysis included 291 participants who were assessed for PTSD and child maltreatment. The sample was 88% male, 48% Aboriginal, with an average age of 17 years (range 13-21 years). One in five (20%) participants were diagnosed with PTSD, with females significantly more likely to have PTSD than males (40% vs. 17%, p

OBJECTIVE To describe prevalence of and risk factors for overweight, obesity and self-perceived weight gain of Aboriginal and non-Aboriginal Australian young people in custody at baseline and over 12 months of follow-up. DESIGN, SETTING AND PARTICIPANTS Prospective cohort study of youths in custody in New South Wales, from August 2009, with follow-up at 3, 6 and 12 months. MAIN OUTCOME MEASURES Body mass index at baseline, categorised as overweight or obese using international cut-points; waist-to-height ratio (WHtR) at baseline, categorised as increased metabolic risk (≥ 0.5) or low metabolic risk (< 0.5); and self-perceived weight change at follow-up. RESULTS At baseline, 452 youths were incarcerated, 361 (79.9%) consented to participate, and complete anthropometry measurements were taken for 303 (67.0%). At 3, 6 and 12 months, there were 231 (76.2%), 158 (52.1%) and 143 (47.2%) participants, respectively. Two-hundred and sixty-four (87.1%) were male, 151 (49.8%) were Aboriginal, and 145 (47.9%) had been incarcerated for < 3 months at baseline. One hundred and forty-five (47.9%) were overweight or obese and 112 (37.0%) had a WHtR of ≥ 0.5 at baseline. However, only 72 (24.1%) perceived themselves as overweight at baseline, and 154 (71.6%) perceived a weight increase since incarceration despite improvements in diet and exercise. Longer incarceration time was strongly associated with overweight and obesity in Aboriginal youths at baseline and with self-perceived weight gain in non-Aboriginal youths at follow-up. CONCLUSIONS Overweight and obesity were highly prevalent but poorly recognised in young people in custody. A longer incarceration time had the strongest association with overweight obesity and self-reported weight gain. From a population health and policy perspective, changes to the liberal food environment and the approach to increasing physical activity in custody are warranted.

Posttraumatic stress disorder (PTSD), a pathologic response to severe stress, is a common co-morbid disorder in substance-dependent individuals. Evidence from twin studies suggests that PTSD is moderately heritable. Genetic association studies to date have reported a limited number of replicated findings. We conducted a candidate gene association study in trauma-exposed individuals within the Comorbidity and Trauma Study's sample (1343 heroin-dependent cases and 406 controls from economically disadvantaged neighborhoods). After data cleaning, the 1430 single nucleotide polymorphisms (SNPs) retained for analyses provided coverage of 72 candidate genes and included additional SNPs for which association was previously reported as well as 30 ancestry-informative markers. We found a functional DRD2 promoter polymorphism (rs12364283) to be most highly associated with PTSD liability [odds ratio (OR) 1.65 (1.27-2.15); P = 1.58 10(-4)]; however, this association was not significant, with a stringent Bonferroni correction for multiple comparisons. The top hits include SNPs from other dopaminergic system genes: DRD2 DRD3, TH and DBH. Additional analyses revealed that the association involving rs12364283 is largely limited to amphetamine-dependent individuals. Substantial risk is observed in amphetamine-dependent individuals, with at least one copy of this SNP [OR 2.86 (1.92-4.27); P = 2.6 10(-7)]. Further analyses do not support extensive mediation of PTSD risk via self-reported impulsivity (BIS total score). These findings suggest roles for impairment in inhibitory control in the pathophysiology of PTSD and raise questions about stimulant use in certain populations (e. g. those in combat).

Borderline personality disorder (BPD) and substance use disorders frequently co-occur; their dual presence predicts poor prognosis. The genetic underpinnings of BPD have not been well-characterized and could offer insight into comorbidity. The current report focuses on the association of neurexin 3 (NRXN3) single nucleotide polymorphisms (SNPs) with BPD symptoms in heroin dependent cases and controls.The sample of the Comorbidity and Trauma Study, a genetic association study of heroin dependence, consists of Australian heroin dependent cases ascertained from opioid replacement therapy clinics and controls ascertained in nearby economically disadvantaged neighborhoods. The assessment included a screening instrument for BPD, used previously in Australian population surveys. Genotypic and BPD phenotypic data were available for 1439 cases and 507 controls. We examined the association of 1430 candidate gene SNPs with BPD phenotypes.One or more NRXN3 SNPs were nominally associated with all BPD phenotypes; however, none met the conservative significance threshold we employed to correct for multiple testing. The most strongly associated SNPs included rs10144398 with identity disturbance (p=4.9×10(-5)) and rs10151731 with affective instability (p=8.8×10(-5)). The strongest association with screening positive for BPD was found for the NRXN3 SNP, rs10083466 (p=.0013). Neither the correlation of BPD phenotypes nor the linkage disequilibrium relationships of the SNPs account for the number of observed associations involving NRXN3 SNPs.Our findings provide intriguing preliminary evidence for the association of NRXN3 with BPD phenotypes. The strongest associations were found for traits (i.e., affective instability; identity disturbance) also observed with other disorders.

Acute kidney injury (AKI) is the new consensus term for acute renal failure. The term describes a continuum of kidney injury, a common condition in the critically ill and after major surgery, which is associated with increased mortality. The incidence of AKI in intensive care unit patients in Australia is >30% and sepsis is a major contributory factor. However, there is limited knowledge about its incidence after major surgery, except for cardiac surgery. The creation of staged AKI classification systems (RIFLE [Risk, Injury, Failure, Loss, End-stage], Acute Kidney Injury Network and the new Kidney Disease: Improving Global Outcomes criteria) has accelerated progress in critical care nephrology research by showing that even small changes in serum creatinine are associated with increased risk of death and that this risk increases progressively with severity of AKI. Recent thought and research has cast doubt over previously accepted pathophysiological views of AKI. Moreover, terms such as ‘prerenal azotaemia’ and ‘acute tubular necrosis’ are now being challenged as lacking validity, having little supportive evidence and carrying limited clinical utility. In this review, we explore the limitations of animal and human models of AKI and the implications of recent research on our current understanding of the pathophysiology of AKI. In addition, we describe conventional and novel diagnostic methods and therapies, and explore the clinical implications of the effect of fluid administration and perioperative management. Finally, we identify priorities for clinical investigations and future directions in AKI research.

Background: Acute exacerbations of COPD (AECOPD) have a significant impact on healthcare utilisation, including physician visits and hospitalisations. The effect of pulmonary rehabilitation (PR) on hospitalisations for AECOPD is inconclusive. Methods: Medical databases were searched to assess the impact of PR on emergency hospitalisations for AECOPD. Cohort studies and randomised controlled trials (RCTs) reporting hospitalisations for AECOPD as an outcome were included. Meta-analyses compared exacerbation rates between eligible PR recipients and non-recipients before and after PR. Results: 18 studies were included in the meta-analysis. Admission rates per person-year were lower in the year following completion of PR. Results from 10 RCTs showed that the control groups had a higher overall rate of exacerbations than the PR groups (0.967, 95% confidence intervals (CIs) 0.669, 1.399 for control versus 0.615 95% CI 0.328, 1.155 for PR). Five studies compared admission numbers in the 12 months before and after PR, finding a significantly higher admission rate before (1.243, 95% CIs 0.661, 2.336) compared to after PR (0.472, 95% CIs 0.280, 0.794). The pooled result of three cohort studies found the reference group had a lower admission rate compared to the PR group (0.184, 95% CI 0.106, 0.317 for reference versus 0.282 95% CI 0.246, 0.323 for PR). Conclusions: Although results from RCTs suggested that PR reduces subsequent exacerbations, pooled results from the cohort studies did not favour PR, likely reflecting the heterogeneous nature of individuals included in observational research and the varying standards of PR programmes.

Multiple myeloma (MM) is the second most common hematologic malignancy and is predominantly a disease of the elderly. In the past 2 decades, a range of new therapeutic options have become available, leading to improvements in patient outcomes, including both attainment of remission and overall survival. These improved outcomes have heralded a paradigm shift from a palliative approach toward more active management, including the use of sequential therapies, with the goal of prolonging progression-free and overall survival and preserving organ function to enable delivery of further therapy at relapse. Until now, most outcome data for MM have come from clinical trials, with few reports available on patients treated outside the clinical trial setting-in the "real world." Clinical trials are routinely undertaken in specialist centers, and extrapolation of these trial data to broader clinical practice might not accurately reflect "real-world" patient outcomes. Optimal management of MM is of key importance for positive patient outcomes, and further scrutiny of the efficacy and safety of the various reported therapies and how clinical trial findings are being translated or applied in the real-world management of MM is required. In the present review, we have described the minimal published evidence available through a comprehensive published data search of MEDLINE using the OvidSP interface on the management and outcomes of MM outside the setting of clinical trials, including evidence on the uptake of new therapies and their efficacy and tolerability in standard practice. Clinical registries might be able to help provide these data in the future.

Objectives: Despite possessing considerable relevance for planning and delivery of effective rehabilitation interventions, systematic evaluation of cognitive function is often ignored in clinical practice. This paper describes a successful method for measuring cognitive function and the nature of cognitive deficits (CD) in people with schizophrenia admitted to psychiatric rehabilitation services. Methods: Data on the cognitive functioning of consecutive patients with schizophrenia / schizoaffective disorder admitted during a 5-year period to a public in-patient rehabilitation facility was collated retrospectively and analysed. The Brief Assessment of Cognition in Schizophrenia (BACS) was used to evaluate cognitive function. Results: It was possible to administer the BACS to 122 of 135 consecutive admissions. The mean composite score on the BACS was 1.8 standard deviations below the norm, and 43% had moderate or severe CD. The BACS sub-tests of list learning and symbol coding revealed more severe deficits. Conclusions: The study indicates that evaluation of cognitive function using brief instruments is feasible in psychiatric rehabilitation settings. Global and domain-specific CD were prevalent among people with schizophrenia. In view of the strong association of cognitive functioning with community functioning and rehabilitation outcomes, further studies exploring the feasibility and utility of routinely evaluating cognitive function are warranted.

Rationale: Exacerbations are key events in Chronic Obstructive Pulmonary Disease (COPD), affecting lung function decline and quality of life. The effect of exposure to different air pollutants on COPD exacerbations is not clear. Objective: To carry out a systematic review examining associations between air pollutants (including gases and particulate matter) and hospital admissions for COPD exacerbations. Methods: MEDLINE, EMBASE, BIOSIS & Science Citation Index, and the Air Pollution Epidemiology Database were searched from 1980 until September 2015. Inclusion criteria focused on studies presenting solely a COPD outcome defined by hospital admissions, and a measure of gaseous air pollutants and particle fractions. The association between each pollutant with COPD admissions was investigated in meta-analyses using random-effects models. Analyses were stratified by geographical clusters to investigate the consistency of the evidence worldwide. Measurements and Main Results: 46 studies were included and results for all the pollutants under investigation showed marginal positive associations; however the number of included studies was small with high heterogeneity between them and there was evidence of small-study bias. Geographical clustering of the effects of pollution on COPD hospital admissions was evident and reduced heterogeneity significantly. The most consistent associations was between a 1mg/m3 increase in carbon monoxide levels with COPD related admissions; Odds Ratio: 1.02 (95%CI: 1.01-1.03). The heterogeneity was moderate and there was a consistent positive association in both Europe and North America, although levels were clearly below WHO guideline values. Conclusions: There is mixed evidence on the effects of environmental pollution on COPD exacerbations. Limitations of previous studies included the low spatio-temporal resolution of pollutants, inadequate control for confounding factors, such as the multi-collinearity of atmospheric pollutants, and the use of aggregated health data that ignore personal characteristics. The need for more targeted exposure estimates in a large number of geographical locations is evident.

In 2011, the US national rate of smoking early in pregnancy was 11.5%. Unfortunately, our home state of Ohio had a rate twice as high at 23%. Smoking in pregnancy remains one of the most important modifiable risk factors for pregnancy complications, specifically preterm birth.The objective of the study was to quantify the preterm birth risk to various trimester-specific smoking behaviors.The study was a population-based, retrospective cohort study of singleton non-anomalous live births, using Ohio birth records 2006 to 2012. Preterm birth rates were compared between non-smokers and women who smoked in the preconception period only, those who quit smoking after the 1st and 2nd trimesters, and those who smoked throughout pregnancy. Multivariate logistic regression quantified the risk of smoking with cessation at various times in pregnancy and preterm birth risk, adjusted for maternal race, education, age, Medicaid use, marital status, and parity. A stratified analysis was performed on the basis of preterm birth subtype: spontaneous preterm birth versus indicated preterm birth. We also performed an additional analysis stratifying for maternal race using the 2 largest categories of race (non-Hispanic white and non-Hispanic black).Of the 913,757 birth records analyzed, nearly 25% of the women reported some smoking behavior on the birth certificate data. Of smokers, less than half quit during pregnancy (38.8% vs 61.2% smoked throughout pregnancy). Early quitters had a similar preterm birth rate compared with non-smokers. Women who smoked through the 1st trimester only did not have a significant increase in their overall preterm birth odds ratio37 weeks; however, it did increase the odds of extreme preterm birth28 weeks by 20% (adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.02, 1.40). Quitting late in pregnancy resulted in the highest odds ratio increase: 70% for preterm birth37 weeks (adjusted odds ratio 1.70; CI, 1.60, 1.80), even after adjustment for the confounding influences. Quitting smoking early in pregnancy after the 1st trimester did not increase the overall risk of spontaneous or indicated preterm birth37 weeks significantly. However, quitting after the 1st trimester was associated with a significant increase in risk of extreme spontaneous preterm birth28 weeks, an effect not seen with indicated preterm birth28 weeks. Delaying cessation until late in pregnancy-after the 2nd trimester-was associated with the highest risk increases, 65% increased odds of spontaneous and 78% increase in odds of indicated preterm births. The rate of preterm births to non-Hispanic black mothers was increased in all categories over those of non-Hispanic white mothers. The relative influence of smoking cessation in pregnancy was similar in black compared with white mothers. The effect modification in the regression model was analyzed and revealed no significant interaction between race and smoking patterns on preterm birth risk.Smoking throughout pregnancy is associated with an increased risk of preterm birth. However, quitting early in pregnancy negates this risk. Widespread programs aimed at smoking cessation early in pregnancy could have a significant impact on reducing the rate of preterm birth nationally.