Conservative kidney management and kidney supportive care: core components of integrated care for people with kidney failure.

Integrated kidney care requires synergistic linkage between preventative care for people at risk for chronic kidney disease and health services providing care for people with kidney disease, ensuring holistic and coordinated care as people transition between acute and chronic kidney disease and the 3 modalities of kidney failure management: conservative kidney management, transplantation, and dialysis. People with kidney failure have many supportive care needs throughout their illness, regardless of treatment modality. Kidney supportive care is therefore a vital part of this integrated framework, but is nonexistent, poorly developed, and/or poorly integrated with kidney care in many settings, especially in low- and middle-income countries. To address this, the International Society of Nephrology has (i) coordinated the development of consensus definitions of conservative kidney management and kidney supportive care to promote international understanding and awareness of these active treatments; and (ii) identified key considerations for the development and expansion of conservative kidney management and kidney supportive care programs, especially in low resource settings, where access to kidney replacement therapy is restricted or not available. This article presents the definitions for conservative kidney management and kidney supportive care; describes their core components with some illustrative examples to highlight key points; and describes some of the additional considerations for delivering conservative kidney management and kidney supportive care in low resource settings.

Childhood growth outcomes 2 years after hypertensive versus normotensive pregnancy: a P4 study.

BACKGROUND: Intrauterine exposure to hypertensive disorders of pregnancy, including gestational hypertension (GH) and preeclampsia (PE), may influence infant growth and have long-term health implications. This study aimed to compare growth outcomes of infants exposed to a normotensive pregnancy (NTP), GH, or PE from birth to 2 years. METHODS: Infants were children of women enroled in the prospective Postpartum Physiology, Psychology and Paediatric (P4) cohort study who had NTP, GH or PE. Birth, 6-month (age-corrected) and 2-year (age-corrected) weight z-scores, change in weight z-scores, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-scores were calculated to assess infant growth (NTP = 240, GH = 19, PE = 66). RESULTS: Infants exposed to PE compared to NTP or GH had significantly lower birth weight and length z-scores, but there were no differences in growth outcomes at 6 months or 2 years. GH and PE-exposed infants had significantly greater weight z-score gain [95% CI] (PE = 0.93 [0.66-1.18], GH = 1.03 [0.37-1.68], NTP = 0.45 [0.31-0.58], p < 0.01) and rapid weight gain (GH = 63%, PE = 59%, NTP = 42%, p = 0.02) from birth to 2 years, which remained significant for PE-exposed infants after confounder adjustment. CONCLUSION: In this cohort, GH and PE were associated with accelerated infant weight gain that may increase future cardiometabolic disease risk. IMPACT: Preeclampsia exposed infants were smaller at birth, compared with normotensive pregnancy and gestational hypertension exposed infants, but caught up in growth by 2 years of age. Both preeclampsia and gestational hypertension exposed infants had significantly accelerated weight gain from birth to 2 years, which remained significant for preeclampsia exposed infants after adjustment for confounders including small for gestational age. Monitoring of growth patterns in infants born following exposure to a hypertensive disorder of pregnancy may be indicated to prevent accelerated weight gain trajectories and obesity.

Estimating a Minimal Important Difference for the EQ-5D-5L Utility Index in Dialysis Patients.

OBJECTIVES: The EQ-5D-5L is a commonly used health-related quality of life instrument for evaluating interventions in patients receiving dialysis; however, the minimal important difference (MID) that constitutes a meaningful treatment effect for this population has not been established. This study aims to estimate the MID for the EQ-5D-5L utility index in dialysis patients. METHODS: 6-monthly EQ-5D-5L measurements were collected from adult dialysis patients between April 2017 and November 2020 at a renal network in Sydney, Australia. EQ-VAS and Integrated Palliative care Outcome Scale Renal symptom burden scores were collected simultaneously and used as anchors. MID estimates for the EQ-5D-5L utility index were derived using anchor-based and distribution-based methods. RESULTS: A total of 352 patients with ≥1 EQ-5D-5L observation were included, constituting 1127 observations. Mean EQ-5D-5L utility index at baseline was 0.719 (SD ± 0.267), and mean EQ-5D-5L utility decreased over time by -0.017 per year (95% CI -0.029 to -0.006, P = .004). Using cross-sectional anchor-based methods, MID estimates ranged from 0.073 to 0.107. Using longitudinal anchor-based methods, MID for improvement and deterioration ranged from 0.046 to 0.079 and -0.111 to -0.048, respectively. Using receiver operating characteristic curves, MID for improvement and deterioration ranged from 0.037 to 0.122 and -0.074 to -0.063, respectively. MID estimates from distribution-based methods were consistent with anchor-based estimates. CONCLUSIONS: Anchor-based and distribution-based approaches provided EQ-5D-5L utility index MID estimates ranging from 0.034 to 0.134. These estimates can inform the target difference or "effect size" for clinical trial design among dialysis populations.

The Association of Frailty and Malnutrition With Dietary Intake and Gastrointestinal Symptoms in People With Kidney Failure: 2-Year Prospective Study.

BACKGROUND: Frailty and malnutrition are both associated with worsening morbidity and mortality and become more prevalent in the elderly and as kidney function declines. Anorexia and reduced oral intake are common features of both frailty and malnutrition. However, there are sparse data evaluating the impact of other gastrointestinal (GI) symptoms, such as taste changes, on rates of frailty and malnutrition in people with kidney failure. The aim of this study is to describe the prevalence of frailty and malnutrition and their association with dietary intake and nutrition-related symptoms in people with kidney failure. METHODS: This observational study recruited people with kidney failure who were commencing Conservative Kidney Management or elderly people (aged > 75 years) newly commenced on dialysis from 3 renal units. Participants underwent assessments of frailty, nutritional status, dietary intake, and GI symptom burden when they attended clinic appointments, approximately every 6 months. RESULTS: Of the 85 participants, 57% were assessed as being frail and 33% were assessed as being malnourished. Participants assessed as frail reported more GI symptoms (3 vs. 2, P < .001) that were more severe (1.75 vs. 1.0, P < .001) compared to nonfrail participants. Being malnourished was associated with a 5 times higher chance of being frail (odds ratio 5.8; 95% confidence interval 1.5, 21.8; P = .015) and having more severe symptoms was associated with a 2 times higher chance (odds ratio 2.8; 95% CI 1.1, 7.0; P = .026) of being frail. In addition to experiencing more GI symptoms, that were more severe, participants who were malnourished consumed significantly less energy (1234 kcal vs. 1400 kcal, P = .01) and protein (51 g vs. 74 g, P < .001). CONCLUSIONS: Frailty and malnutrition are common and are associated with a higher GI symptom burden and poorer dietary intake. Future research is needed to determine effective interventions targeting frailty and malnutrition, including nutrition-related symptoms and optimal protein intake.

Carbon emissions and hospital pathology stewardship: a retrospective cohort analysis.

BACKGROUND: As healthcare is responsible for 7% of Australia's carbon emissions, it was recognised that a policy implemented at St George Hospital, Sydney, to reduce non-urgent pathology testing to 2 days per week and, on other days only if essential, would also result in a reduction in carbon emissions. The aim of the study was to measure the impact of this intervention on pathology collections and associated carbon emissions and pathology costs. AIMS: To measure the impact of an intervention to reduce unnecessary testing on pathology collections and associated carbon emissions and pathology costs. METHODS: The difference in the number of pathology collections, carbon dioxide equivalents (CO2 e) for five common blood tests and pathology cost per admission were compared between a 6-month reference period and 6-month intervention period. CO2 e were estimated from published pathology CO2 e impacts. Cost was derived from pathology billing records. Outcomes were modelled using multivariable negative binomial, generalised linear and logistic regression. RESULTS: In total, 24 585 pathology collections in 5695 patients were identified. In adjusted analysis, the rate of collections was lower during the intervention period (rate ratio 0.90; 95% confidence interval (CI), 0.86-0.95; P < 0.001). This resulted in a reduction of 53 g CO2 e (95% CI, 24-83 g; P < 0.001) and $22 (95% CI, $9-$34; P = 0.001) in pathology fees per admission. The intervention was estimated to have saved 132 kg CO2 e (95% CI, 59-205 kg) and $53 573 (95% CI, 22 076-85 096). CONCLUSIONS: Reduction in unnecessary hospital pathology collections was associated with both carbon emission and cost savings. Pathology stewardship warrants further study as a potentially scalable, cost-effective and incentivising pathway to lowering healthcare associated greenhouse gas emissions.

Factors associated with quality of life in patients with kidney failure managed conservatively and with dialysis: a cross-sectional study.

BACKGROUND: Later stage chronic kidney disease (CKD) is associated with poorer self-perceived health-related quality of life (HRQOL), a major consideration for many patients. Psychological factors such as depression and anxiety have been linked with poorer HRQOL. We aimed to determine if anxiety or depressive symptoms are significantly associated with self-perceived health-related quality of life, in patients with CKD Stage 5. The secondary aim was to determine which patient-associated factors are associated with HRQOL in patients with CKD Stage 5. METHODS: This retrospective cross-sectional study included patients that attended the St George Hospital Kidney Supportive Care (KSC) clinic between 1 and 2015 and 30 June 2022 with CKD Stage 5 (either conservatively-managed or receiving dialysis). Patients completed surveys of their functional 'domains' and quality of life (EQ-5D-5L) and symptom surveys (IPOS-Renal) at their first visit. We performed multivariable linear regression analysis with the outcome of interest being HRQOL, measured using the EQ-VAS, a continuous 100-point scale, for patients undergoing conservative management or dialysis. Pre-specified variables included age, sex, eGFR (for those conservatively-managed), "feeling depressed" (IPOS-Renal), "feeling anxious" (IPOS-Renal) and "anxiety/depression" (EQ-5D-5L). RESULTS: We included 339 patients. 216 patients received conservative kidney management (CKM) and 123 patients received dialysis. Patients receiving CKM were significantly older than those on dialysis, (median age 83 years vs. 73 years, p < 0.001). For conservatively-managed patients, variables independently associated with poorer EQ-VAS were difficulty performing usual activities (EQ-5D-5L), drowsiness (IPOS-Renal) and shortness of breath (IPOS-Renal). For patients receiving dialysis, variables that were independently associated with poorer EQ-VAS were reduced ability to perform self-care (EQ-5D-5L) and lack of energy (IPOS-Renal). Anxiety and depressive symptoms were not significantly associated with poorer EQ-VAS for either group of patients. CONCLUSIONS: Symptoms associated with reduced HRQOL include shortness of breath, drowsiness and impaired functional ability. Optimization of multidisciplinary teams focusing on these issues are likely to be of benefit.

Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases.

A comprehensive understanding of the mechanisms involved in epigenetic changes in gene expression is essential to the clinical management of diseases linked to the SMYD family of lysine methyltransferases. The five known SMYD enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine (SAM) to specific lysines on histones and non-histone substrates. SMYDs family members have distinct tissue distributions and tissue-specific functions, including regulation of development, cell differentiation, and embryogenesis. Diseases associated with SMYDs include the repressed transcription of SMYD1 genes needed for the formation of ion channels in the heart leading to heart failure, SMYD2 overexpression in esophageal squamous cell carcinoma (ESCC) or p53-related cancers, and poor prognosis associated with SMYD3 overexpression in more than 14 types of cancer including breast cancer, colon cancer, prostate cancer, lung cancer, and pancreatic cancer. Given the importance of epigenetics in various pathologies, the development of epigenetic inhibitors has attracted considerable attention from the pharmaceutical industry. The pharmacologic development of the inhibitors involves the identification of molecules regulating both functional SMYD SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domains, a process facilitated by available X-ray structures for SMYD1, SMYD2, and SMYD3. Important leads for potential pharmaceutical agents have been reported for SMYD2 and SMYD3 enzymes, and six epigenetic inhibitors have been developed for drugs used to treat myelodysplastic syndrome (Vidaza, Dacogen), cutaneous T-cell lymphoma (Zoinza, Isrodax), and peripheral T-cell lymphoma (Beleodag, Epidaza). The recently demonstrated reversal of SMYD histone methylation suggests that reversing the epigenetic effects of SMYDs in cancerous tissues may be a desirable target for pharmacological development.

Airwave oscillometry to measure lung function in children with Down syndrome.

BACKGROUND: Children with Down syndrome are at risk for significant pulmonary co-morbidities, including recurrent respiratory infections, dysphagia, obstructive sleep apnea, and pulmonary vascular disease. Because the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities, we sought to assess the feasibility of both airwave oscillometry and spirometry in children with Down syndrome. METHODS: Thirty-four children with Down syndrome aged 5-17 years were recruited. Participants performed airwave oscillometry and spirometry before and 10 min after albuterol. Outcomes include success rates, airway resistance and reactance pre- and post-bronchodilator, and bronchodilator response. RESULTS: Participants were median age 9.2 years (interquartile range 7.2, 12.0) and 47% male. Airwave oscillometry was successful in 26 participants (76.5%) and 4 (11.8%) were successful with spirometry. No abnormalities in airway resistance were detected, and 16/26 (61.5%) had decreased reactance. A positive bronchodilator response by oscillometry was observed in 5/23 (21.7%) of those with successful pre- and post-bronchodilator testing. CONCLUSIONS: Measures of pulmonary function were successfully obtained using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population. IMPACT: Children with Down syndrome are at risk for significant pulmonary co-morbidities, but the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities. This may limit the population's enrollment in clinical trials and in standardized clinical care. In this prospective study of lung function in children with Down syndrome, airwave oscillometry was successful in 76% of participants but spirometry was successful in only 12%. This study reinforces that measures of pulmonary function can be obtained successfully using airwave oscillometry in children with Down syndrome, which supports its use in this high-risk population.

Temporal changes and risk factors for death from early withdrawal within 12 months of dialysis initiation-a cohort study.

BACKGROUND: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses. RESULTS: Of 32 274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral and the presence of cerebrovascular disease; obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease and cancers were associated with early medical withdrawals. CONCLUSIONS: Death from dialysis withdrawal accounted for >30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.

Optimising mothers' health behaviour after hypertensive disorders of pregnancy: a qualitative study of a postnatal intervention.

BACKGROUND: Hypertensive disorders of pregnancy have longer-term implications, increasing women's lifetime cardiovascular disease risk. The Blood Pressure Postpartum study is a multi-centre randomised three-arm trial of interventions, ranging in intensity and including education and lifestyle coaching, to support women to maintain or adopt healthy eating and physical activity during the first postpartum year. This qualitative sub-study nested within the main trial aimed to investigate whether and how women adopted healthy behaviours after a pregnancy complicated by a hypertensive disorder. METHODS: Semi-structured telephone interviews were recorded, transcribed and analysed thematically, following Braun and Clarke principles. They explored behaviour change among new mothers following their hypertensive pregnancy, and the intervention's effect on their capacity and motivation to pursue healthy lifestyles. RESULTS: Thirty-four women from all three trial arms participated at 10-12 months postpartum. The three main themes were 1) Awareness of cardiovascular risk: some did not acknowledge the health risks, whereas others embraced this information. 2) Sources of motivation: while the majority were motivated to make a concerted effort to adapt their health behaviour, motivation often centred on their baby and family rather than their own needs. 3) Sustaining behaviour change with a new baby: women in the more intensive intervention arm demonstrated increased recognition of the importance of reducing cardiovascular health risks, with greater motivation and guidance to change their health behaviour. There was minimal evidence of crossover amongst groups, with women largely accepting their randomised level of intervention and not seeking additional help when randomised to minimal intervention. CONCLUSIONS: Among women participating in an early post-hypertensive disorders of pregnancy randomised controlled trial aimed at improving their cardiovascular disease risk profile, the majority recognised the future health risks and appeared motivated to improve their lifestyle, particularly women in the highest-intensity intervention group. This highlights the importance of structured support to assist women embrace healthy lifestyles especially during the challenges of new parenthood. TRIAL REGISTRATION: The Blood Pressure Postpartum study was prospectively registered as a clinical trial with the Australian New Zealand Clinical Trials Registry (anzctr.org.au) on 13 December 2018 (registration number: ACTRN12618002004246).

A Novel Clinical Tool for the Management of Taste Changes in Patients With Chronic Kidney Disease: The Chronic Kidney Disease Taste Plate.

Taste alteration is a common, but poorly understood, symptom in end-stage kidney disease. The pathophysiology of taste alteration is complex; to date, management has been largely empirical. As our understanding of pathophysiology grows so does the evidence base for its management. This article introduces a clinical tool-the CKD Taste Plate-to assist clinicians in directing management to the underlying pathophysiology of taste alterations in chronic kidney disease.

A Text Messaging Intervention for Dietary Behaviors for People Receiving Maintenance Hemodialysis: A Feasibility Study of KIDNEYTEXT.

RATIONALE & OBJECTIVE: An important component of hemodialysis management involves delivery of complex dietary recommendations. The aim of this study was to determine the feasibility of a mobile phone text-message intervention to improve dietary behavior in people undergoing hemodialysis. STUDY DESIGN: Six-month randomized feasibility study. SETTING & PARTICIPANTS: Patients receiving maintenance hemodialysis across 2 health districts in Sydney, Australia. INTERVENTIONS: Participants randomized to the intervention received 3 text messages per week in addition to standard dietary care for 6 months. The usual care group received standard dietary care. OUTCOMES: The primary outcomes were feasibility measured using recruitment and retention rates, acceptability of the intervention, and adherence to dietary recommendations. Secondary exploratory outcomes included information on certain clinical parameters related to dietary management of patients receiving maintenance hemodialysis. RESULTS: 130 people were recruited; 48% of eligible patients (130 of 272) consented to participate, and 88% (115 of 130) completed the study. Semistructured interviews evaluating acceptability identified 5 themes: clear and comprehensive, engaging with consistent and relevant content, maintaining attention with timely reminders, sustaining interest through ongoing care, and generic messages inadequate to prompt dietary change. There was no difference in adherence to dietary recommendations across treatment groups (odds ratio, 1.21 [95% CI, 0.55-2.72]; P = 0.6). Secondary exploratory analyses suggested reductions in dietary intake of single nutrients (potassium, phosphorus, sodium, protein), interdialytic weight gain, and phosphate binder use among intervention participants compared with participants assigned to standard care. LIMITATIONS: Our feasibility study was of short duration. Adherence was based on self-reported data. Generalizability to populations receiving maintenance hemodialysis outside of an urban, Australian setting is unknown. CONCLUSIONS: A simple mobile phone text-messaging intervention was feasible and acceptable to patients. Further investigation of the impact on patient-reported and clinical outcomes is warranted. FUNDING: Funding for the study was provided by a Sydney Medical School Foundation Grant and the Centre for Transplant and Renal Research at Westmead Hospital. TRIAL REGISTRATION: Registered at Australian New Zealand Clinical Trials Registry with study number ACTRN12617001084370.

Prevalence, types and recognition of cognitive impairment in dialysis patients in South Eastern Sydney.

BACKGROUND: In international studies, cognitive impairment is a common but underdetected issue in dialysis patients. Chronic kidney disease (CKD) shares risk factors with and is an independent risk factor for cognitive impairment. There is a lack of Australian data on cognitive impairment in this at-risk population. This has implications on service planning because cognitive impairment in CKD is associated with higher mortality, morbidity and healthcare costs. AIMS: To examine the prevalence, types and clinician recognition of cognitive impairment within an Australian dialysis population. METHODS: A cross-sectional study of haemodialysis and peritoneal dialysis patients in South Eastern Sydney screened for cognitive impairment using the Montreal Cognitive Assessment (MoCA). Participant interviews, medical records, physician and carer questionnaires, were used to determine the types of cognitive impairment and rate of recognition. RESULTS: One hundred and six participants were included (median age 66 years, median dialysis duration 2 years) and 58 (54.7%) were cognitively impaired on the MoCA, of whom old age psychiatrists sub-classified 21 (36.2%) as having dementia, and 31 (53.4%) with 'cognitive impairment, no dementia'; 36/58 (62.0%) of the cognitively impaired participants on the MoCA were suspected of having cognitive impairment by nephrologists but only 14/58 (24.1%) had this documented in medical records. CONCLUSION: Although cognitive impairment is common in dialysis patients, there are low levels of detection by clinical teams. Cognitive screening of dialysis patients should be incorporated as part of wider assessment and determination of management goals such as individuals' capacity to self-care and provide informed consent to treatments.

Prevalence of Taste Changes and Association with Other Nutrition-Related Symptoms in End-Stage Kidney Disease Patients.

OBJECTIVES: Gastrointestinal symptoms are common in end-stage kidney disease (ESKD) and have been associated with reduced health-related quality of life and malnutrition. The aim of this study is to describe the prevalence of taste changes in an ESKD population and to evaluate whether taste changes are associated with the presence or severity of other nutrition-related symptoms and malnutrition. METHODS: We conducted a retrospective audit of people with ESKD on conservative, nondialysis management or renal replacement therapy who had completed a taste change assessment. Taste change was assessed on a Likert scale from none to overwhelming. Descriptions of taste changes were also collected. Other outcomes included gastrointestinal symptoms collected using the iPOS-renal symptom inventory, nutritional status, and biochemical parameters. RESULTS: In total, 298 patients were included in our analysis. Taste changes were reported in 38% of this cohort. Taste changes were significantly associated with upper gastrointestinal symptoms (nausea, vomiting, anorexia, and dry/sore mouth) and malnutrition. CONCLUSIONS: Our findings indicate that taste changes are highly prevalent and probably under-recognized in ESKD. Further investigation of the association with malnutrition is needed. Future trials are needed to evaluate strategies to manage taste changes in this population.

The long-term cardiovascular impact of hypertension in pregnancy - A missed opportunity.

Women who have had hypertension in pregnancy, both pre-eclampsia and gestational hypertension, have a two- to three-fold increased risk of cardiovascular disease later in life. It is unclear whether this is an unmasking of latent risk, the result of damage to the vascular tree during pregnancy, or both. Irrespective of the underlying pathophysiology, these women are uniquely identified sufficiently early in their lives for lifestyle interventions, if adopted, to improve their long-term health. Currently, follow-up of these women is inadequate and implementation of a coordinated follow-up program, and further research into how best to provide it, is urgently needed.

The lysine methyltransferase SMYD2 is required for normal lymphocyte development and survival of hematopoietic leukemias.

The five membered SET and MYND Domain-containing lysine methyltransferase (SMYD) family plays pivotal roles in development and proliferation. Initially characterized within the cardiovascular system, one such member, SMYD2, has been implicated as an oncogene in leukemias deriving from flawed hematopoietic stem cell (HSC) differentiation. We show here that conditional SMYD2 loss disrupts hematopoiesis at and downstream of the HSC via both apoptotic loss and transcriptional deregulation of HSC proliferation and disruption of Wnt-ß-Catenin signaling. Yet, previously documented SMYD2 cell cycle targets were unscathed. Turning our analysis to human leukemias, we observed that SMYD2 is highly expressed in CML, MLLr-B-ALL, AML, T-ALL, and B-ALL leukemias and its levels in B-ALL correlate with poor survival. SMYD2 knockdown results in apoptotic death and loss of anchorage-independent transformation of each of these hematopoietic leukemias. These data provide an underlying mechanism by which SMYD2 acts during normal hematopoiesis and as a proto-oncogene in leukemia.

School-supervised use of a once-daily inhaled corticosteroid regimen: A cluster randomized trial.

BACKGROUND: School-supervised use of a once-daily inhaled corticosteroid regimen (supervised therapy) can improve medication adherence and asthma control. OBJECTIVE: We sought to evaluate the effectiveness of supervised therapy in a unique setting and population. METHODS: We conducted a cluster randomized trial of supervised therapy in 20 elementary schools with a disproportionate enrollment of low-income Latino students. Schools were purposively selected, matched, and randomized to receive 9 months of supervised therapy with mometasone furoate or usual care. All English- or Spanish-speaking students with self-reported asthma were eligible. The Asthma Control Questionnaire (ACQ) was interviewer administered quarterly at school. Students in supervised therapy schools were hypothesized to have lower ACQ scores than students in usual-care schools. RESULTS: Of 393 enrolled students, 189 students receiving immediate intervention and 143 students receiving delayed intervention provided 1 or more ACQ data points, were between 6 and 10 years of age, and were included in the primary analysis. At baseline, 39% of students reported taking a controller medication, and 24% had well-controlled asthma. Eighty percent of students receiving immediate intervention were prescribed mometasone. Schools administered 98% of prescribed doses when students attended school. Absences, weekends, and holidays reduced calendar adherence to 53%. During the first year, the mean ACQ score for students receiving immediate and delayed intervention was 1.55 (95% CI, 1.41-1.70) and 1.64 (95% CI, 1.47-1.80), respectively. The estimated treatment effect was -0.08 (95% CI, -0.31 to 0.14). DISCUSSION: Compared with usual care, supervised therapy did not improve asthma control among this population of Latino students. Additional research is warranted to confirm these results.

In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells.

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.

Medical complications of homelessness: a neglected side of men's health.

BACKGROUND: Homelessness is an increasing societal and health issue associated with high rates of substance abuse and mental health disorders. Homeless people die more often and at a younger age than others. AIM: To identify health needs and improve healthcare for homeless men. METHODS: A physician-led clinic was established on-site at the Mission Australia Centre in Sydney, incorporating: (i) liver screening, including portable fibroscan testing, and on-site treatment of hepatitis C; (ii) a mental health clinic, staffed by a psychiatrist; and (iii) a nurse-led clinic to follow up medical issues and deliver vaccinations. Patient data were recorded prospectively to determine what medical problems were encountered so as to drive future healthcare planning. RESULTS: A total of 257 men was assessed between November 2011 and December 2017. In that time, 561 men resided at the Centre. Of these 257 men who attended the clinic, 61% were <45 years old; 69% were current and 8% former smokers; 62% had a history of chronic alcoholic abuse and 66% other substance abuse; 64% had one or more of depression, anxiety, psychosis or another mental health disorder and 44% had metabolic syndrome features, 38% cardiovascular disease, 29% hepatitis C and 21% a respiratory disorder. CONCLUSION: The main health needs of homeless men fall into the categories of mental health; cardiovascular, respiratory and metabolic disorders and addictions and hepatitis C. Establishing on-site clinics at homeless shelters with expertise to address these issues will likely improve the well-being of these men, reduce hospital admissions and prolong their lives.

Prevalence, detection and associations of depression in Australian dialysis patients.

OBJECTIVE: Depression in dialysis patients is often undetected despite associations with poor outcomes. The aim was to determine the prevalence and associations of depressive symptoms and physician recognition of depression within a typical Australian dialysis population. METHOD: A cross-sectional study examined haemodialysis and peritoneal dialysis patients of two hospitals in Sydney. Participants were screened for depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: One hundred and ten patients completed the HADS. Subjects had a mean age of 63.7 years, 37% from a culturally and linguistically diverse background, and median dialysis duration of 2 years. Forty-one per cent of participants had significant depressive symptoms, of whom 42% had been diagnosed with depression by their clinicians. After adjustment for sociodemographic factors, having >10 medications prescribed, >3 hospitalisations in the last 12 months, and a history of depression were associated with depression. CONCLUSION: Depressive symptoms are prevalent in Australian dialysis patients. Robust evidence is needed on the effectiveness of treatments for depression in changing outcomes in chronic kidney disease.