“Acute urinary antibiotics”—A simple metric to identify outpatient antibiotic stewardship opportunities in renal transplant

Background: International Classification of Diseases, Tenth Edition (ICD-10) data help track outpatient antibiotic prescribing but lack validation in immunocompromised populations or subspecialty clinics for this purpose. Asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) are important stewardship targets in renal transplant (RT) patients, but they may require alternative metrics to best monitor prescribing patterns. We describe ICD-10 utilization for RT clinic encounters in which antibiotics were prescribed. We developed a metric classifying “acute urinary antibiotics” (AUA) to track antibiotic use for ASB and UTI, and we validated systematic identification of AUA to enable practical implementation. Methods: We examined RT clinic visit and telemedicine encounters from 2018 to 2021 conducted 1 month after transplant. This project was deemed non–human-subjects research by the Stanford Panel on Human Subjects in Medical Research. Results: The analytic cohort included 420 antibacterial prescriptions from 408 encounters (Fig. 1). Of 238 patients, 136 (57%) were male and 112 (47%) were Hispanic or Latino. The most common primary ICD-10 code was Z94.0 (kidney transplant status) (N = 302 of 408 encounters, 75%); 26 encounters (6%) were coded for UTI (eg, N39.0, urinary tract infection, site not specified); and 214 encounters (53%) had multiple ICD-10 codes. The R82.71 code (bacteriuria) was never used. However, 215 prescriptions (51%) were classified as AUA (Fig. 2). The validation cohort included 130 prescriptions; 59 (45%) were classified as AUA and 51 (39%) had documented intent to treat ASB or UTI (positive percent agreement, 83%; negative percent agreement, 97%) (Table 1). For patients >1 month after transplant, the positive percent agreement was 95% and the negative percent agreement was 98%. Of 51 patients receiving AUA, 32 (63%) were asymptomatic despite frequently having a code for UTI (Fig. 3). Conclusions: ICD-10 coding may not be helpful in monitoring antibiotic prescribing in RT patients. The AUA metric offers a practical alternative to track antibiotic prescribing for urinary syndromes and reliably correlates with physician intent. Monitoring AUA prescribing rates could help identify opportunities to optimize antibiotic use in this complex outpatient setting

Implementation of a diabetes in pregnancy clinical register in a complex setting: findings from a process evaluation

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.Renae Kirkham, Cherie Whitbread, Christine Connors, Elizabeth Moore, Jacqueline A. Boyle, Richa Richa, Federica Barzi, Shu Li, Michelle Dowden, Jeremy Oats, Chrissie Inglis, Margaret Cotter, Harold D. McIntyre, Marie Kirkwood, Paula Van Dokkum, Stacey Svenson, Paul Zimmet, Jonathan E. Shaw, Kerin O'Dea, Alex Brown, Louise Maple-Brown, on behalf of the Northern Territory Diabetes in Pregnancy Partnershi

Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study

Abstract Background: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Methods/Design: Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal postpartum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. Discussion: This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring

Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study

Abstract Background: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Methods/Design: Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal postpartum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. Discussion: This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Diabetes prevalence and determinants in Indigenous Australian populations: A systematic review

Aims: To perform a systematic review of the prevalence of diabetes and impaired glucose tolerance (IGT) in Indigenous Australians in order to clarify overall patterns, by determinants such as age, gender, region, ethnicity and remoteness. Methods: The OVID interface to Medline and the Australian Indigenous Health. InfoNet databases were systematically searched from years 1997 to 2010. Studies reporting diabetes prevalence were included if they used population-based samples of Indigenous Australians. Diagnosis of diabetes was based on self-report or standard diagnostic criteria. Results: Twenty-four studies were included. The diabetes prevalence ranged from 3.5 to 33.1%; IGT estimates ranged from 4.7 to 21.1%. Prevalence was greater among Indigenous Australian women compared to men, the Northern Territory's Top End compared to Central Australia, Torres Strait Islanders compared to Aboriginals, older (≥35 years) compared to younger

Liver transplant candidates have impaired quality of life across health domains as assessed by computerized testing

Introduction and objectives: Liver transplantation candidates are among the most comorbid patients awaiting lifesaving intervention. Health related quality of life (HRQOL) measured by instruments that incorporate dynamic computerized adaptive testing, could improve their assessment. We aimed to determine the feasibility of administration of the Patient-Reported Outcomes Measurement Information System (PROMIS-CAT) in liver transplant candidates. Materials and methods: Liver transplantation candidates were prospectively enrolled following a review of their available medical history. Subjects were given a tablet computer (iPad) to access the pre-loaded PROMIS CAT. Results: 109 candidates with mean age 55.6 ± 8.6 years were enrolled in this pilot study. Mean MELD-Na score was 16.3 ± 6.3; 92.6% had decompensated liver disease. Leading etiologies of cirrhosis included hepatitis C (34.8%), nonalcoholic steatohepatitis (25.7%) and alcohol (21.1%). Subjects with MELD-Na score > 20 had the most significant impairment in HRQOL (anxiety/fear + 5.9 ± 2.7, p = 0.0289, depression + 5.1 ± 2.5, p = 0.0428, fatigue + 4.3 ± 2.6, p = 0.0973) and physical impairment (−7.8 ± 2.5, p = 0.0022). Stage of cirrhosis and decompensated liver disease were predictive of impaired HRQOL but Child–Pugh Turcotte score was not. Hepatic encephalopathy was the strongest independent predictor of impaired HRQOL, with significant impairment across all domains of health. Conclusions: Liver transplant candidates have significantly impaired HRQOL across multiple domains of health as measured by PROMIS-CAT. HRQOL impairment parallels disease severity. Future study is needed to determine how best HRQOL could be systematically included in liver transplantation listing policy, especially in those candidates with hepatic encephalopathy

High-energy diet and shorter light exposure drives markers of adipocyte dysfunction in visceral and subcutaneous adipose depots of psammomys obesus

Dysfunctional adipose tissue phenotype underpins type 2 diabetes mellitus (T2DM) development. The disruption of circadian rhythms contributes to T2DM development. We investigated the effects of high-energy diet and photoperiod length on visceral and subcutaneous adipose tissue phenotype. Psammomys obesus sand rats exposed to neutral (12 light:12 dark) or short (5 light:19 dark) photoperiod were fed a low- (LE) or high- (HE) energy diet. The HE diet and/or short photoperiod reduced subcutaneous expression of adipocyte differentiation/function markers C/ebpα, Pparδ, Pparγ and Adipoq. Visceral Pparα levels were elevated in the 5:19HE group; however, the HE diet and/or short photoperiod decreased visceral Pparγ and Adipoq expression. 5:19HE animals had elevated Ucp1 yet lower Pgc-1α levels. The HE diet increased visceral Tgf-β1, Ccl2 and Cd68 levels, suggestive of a pro-inflammatory state. Daily visceral rhythms of these genes were affected by a short photoperiod and/or HE diet. The 12:12HE, 5:19LE or 5:19HE animals had a higher proportion of larger adipocytes, indicating increased adipocyte hypertrophy. Collectively, the HE diet and/or shorter light exposure drives a dysfunctional adipose tissue phenotype. Daily rhythms are affected by a short photoperiod and HE diet in a site-specific manner. These findings provide mechanistic insight on the influence of disrupted circadian rhythms and HE diet on adipose tissue phenotype