To understand differences in anti-factor-Xa levels produced by two different dosing strategies (conventional and individualized) for therapeutic enoxaparin in a cohort of hospital inpatients. A multicenter, retrospective cohort study over a two- and a half-year period for inpatients with stable renal function and on therapeutic enoxaparin. Anti-factor-Xa levels were taken 3-5 h after enoxaparin administration and a minimum of 48 h of dosing. The final analysis included 278 patients from five hospitals: conventional dosing was used for 141, while 137 were given an unconventional dose, that is, individualized for their renal function and weight. Out-of-range levels were frequent (35% to 40% of all inpatients). After adjustment for age, renal function, and body mass index (BMI), the conventional group was more likely to experience above-range levels (> 1.0 IU/mL; OR 2.50 [95% CI 1.38-4.56], p < 0.003) than the individualized group. Individualized dosing was independently associated with higher odds of a below-range anti-Xa level (< 0.5 IU/mL) compared to conventional dosing (OR 2.27 [95% CI 1.07-4.76], p = 0.03). Within the conventional group, above-range levels were significantly and independently associated with decreasing renal function (OR 0.97, 95% CI 0.96-0.99, p = 0.004) and with increasing BMI (OR 1.06, 95% CI 1.01-1.10, p = 0.02). No such associations were seen with an individualized approach. Clinical event rates were low and not different between groups (p > 0.24). Conventional therapeutic dosing of enoxaparin exposed people with obesity or renal impairment to more frequent above-range anti-factor-Xa levels; individualizing the dose could improve this but might expose people to subtherapeutic levels. More research is needed.

Introduction and Objective: Asian Indians have increased insulin resistance, more rapid β-cell decline & higher T2D risk. Early interventions targeting these factors can prevent T2D. We compared the effects of a low carbohydrate, low saturated fat (LC) diet to a high unrefined carbohydrate, low fat (HC) diet on β-cell function, insulin sensitivity & fat distribution in Asian Indians with prediabetes. Methods: 53 Asian Indians with prediabetes by ADA criteria (58% males; mean[SD] age 40[6] yrs; BMI 30.4[3.1] kg/m2; fasting glucose 5.7[0.6] mmol/L; 2h postprandial glucose, 2hPG 9.3[2.3] mmol/L) were randomized to a hypocaloric LC diet (20% energy from carbohydrate, 30% protein, 50% fat [<10% saturated fat]) or energy-matched HC diet (50% carbohydrate, 20% protein, 30% fat [<10% saturated fat]), combined with aerobic & resistance exercise 3h/wk for 24 weeks. OGTTs at week 0, 8 and 24 assessed insulin sensitivity (Matsuda ISI) and secretion (Insulinogenic Index, IGI) from 0-30min incremental C-peptide/glucose to derive β-cell function corrected for prevailing insulin sensitivity (Disposition Index, DI). Body composition was measured by MRI, MRS & DXA. Results: 40 participants (LC 22, HC 18) completed the study. Compared to HC, LC had greater increases in DI (EMM[95%CI]; LC 474[294,655], HC 239[47,431], p=0.03) and ISI (LC 3.5[2.0,4.9], HC 1.7 [0.1,3.2], p=0.04), and reductions in fasting insulin (LC -7.8[-10.6,-5], HC -4.1[-6.9,-1.2] mU/L, p=0.045) and glucose (LC -0.5[-0.8,-0.2], HC-0.4 [-0.7,-0.1] mmol/L, p=0.05). LC lowered weight (LC -9.7[-12.3,-7.1], HC -6.5[-9.2,-3.7] kg, p=0.01), liver fat (LC -9.5[-13,-6], HC -6.5[-10.1,-2.9] %, p<0.001) and subcutaneous abdominal fat (LC -1328[-1695,-961], HC -892[-1279,-504] cc, p=0.03) more than HC. VAT, IMCL, IMAT, pancreatic fat, 2hPG, blood pressure & lipids fell similarly in both groups (p≥0.18). Conclusion: In Asian Indians, LC improved β-cell function & insulin sensitivity, highlighting its superiority for T2D prevention. J. Tay: None. G.D. Brinkworth: None. S. Sendhil Velan: None. C. Khoo: None. S. Sadananthan: None. B. Gower: None. C.H. Thompson: None. National Medical Research Council, Ministry of Health, Singapore (MOH-000322-00 and MOH-000858-00); the Agency for Science, Technology and Research, Singapore (C220314028); and the Almond Board of California, US (DIA-19-TAYJ-NR-01)

Background A variety of unsupervised learning algorithms have been used to phenotype older patients, enabling directed care and personalised treatment plans. However, the ability of the clusters to accurately discriminate for the risk of older patients, may vary depending on the methods employed. Aims To compare seven clustering algorithms in their ability to develop patient phenotypes that accurately predict health outcomes. Methods Data was collected for N = 737 older medical inpatients during their hospital stay for five different types of medical data (ICD-10 codes, ATC drug codes, laboratory, clinic and frailty data). We trialled five unsupervised learning algorithms (K-means, K-modes, hierarchical clustering, latent class analysis (LCA), and DBSCAN) and two graph-based approaches to create separate clusters for each method and datatype. These were used as input for a random forest classifier to predict eleven health outcomes: mortality at one, three, six and 12 months, in-hospital falls and delirium, length-of-stay, outpatient visits, and readmissions at one, three and six months. Results The overall median area-under-the-curve (AUC) across the eleven outcomes for the seven methods were (from highest to lowest) 0.758 (hierarchical), 0.739 (K-means), 0.722 (KG-Louvain), 0.704 (KNN-Louvain), 0.698 (LCA), 0.694 (DBSCAN) and 0.656 (K-modes). Overall, frailty data was most important data type for predicting mortality, ICD-10 disease codes for predicting readmissions, and laboratory data the most important for predicting falls. Conclusions Clusters created using hierarchical, K-means and Louvain community detection algorithms identified well-separated patient phenotypes that were consistently associated with age-related adverse health outcomes. Frailty data was the most valuable data type for predicting most health outcomes.

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units. Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. The hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity score matching (PSM) using 17 variables. Results: Of the 3004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty, and had higher pneumonia severity compared to those admitted under a Respiratory unit (p < 0.05). Unadjusted analysis revealed a shorter median LOS among GM-admitted patients (5.9 vs. 4.1 days, p < 0.001). After PSM adjustment, patients admitted under the Respiratory units had an 8-fold higher odds of a longer LOS compared to GM (adjusted odds ratio [aOR] 8.53, 95% CI 1.96–37.25, p = 0.004). Other clinical outcomes were comparable between the two groups. Conclusions: Our findings indicate that GM units compared to Respiratory units provide efficient and safe care for patients requiring hospitalisation for CAP.

Background/Objectives: Community-acquired pneumonia (CAP) is a leading cause of hospitalisations worldwide. Micronutrient deficiencies may influence CAP risk and severity, but their impact on CAP outcomes remains unclear. This study investigated the influence of multivitamin use on hospital length of stay (LOS), intensive care unit (ICU) admission, in-hospital mortality, and 30-day readmissions in hospitalised CAP patients. Methods: This retrospective cohort study included all CAP admissions, identified using ICD-10-AM codes, at two tertiary hospitals in Australia between 2018 and 2023. Pneumonia severity was determined using the CURB65 score, while frailty and nutritional status were assessed using the Hospital Frailty Risk Score (HFRS) and the Malnutrition Universal Screening Tool (MUST). Multivitamin use at admission was identified through the hospital pharmacy database. Propensity score matching (PSM) controlled for 22 confounders and the average treatment effect on the treated (ATET) was determined to evaluate clinical outcomes. Results: The mean (SD) age of the 8162 CAP cases was 75.3 (17.5) years, with 54.7% males. The mean (SD) CURB65 score was 1.9 (1.0), with 29.2% having severe CAP (CURB65 ≥ 3). On admission, 563 patients (6.9%) were on multivitamin supplements. Multivitamin users were younger, had more comorbidities, higher frailty, and higher socioeconomic status than non-users (p < 0.05). The ATET analysis found no significant differences in LOS (aOR 0.14, 95% CI 0.03–5.98, p = 0.307), in-hospital mortality (aOR 1.04, 95% CI 0.97–1.11, p = 0.239), or other outcomes. Conclusions: Multivitamin use was documented in 6.9% of CAP patients and was associated with multimorbidity and frailty but not with improved clinical outcomes. Further research is needed to determine if specific vitamin supplements may offer benefits in this population.

INTRODUCTION:Community-acquired pneumonia (CAP) is a leading cause of hospitalisation and is associated with a high mortality. Vitamin C is a powerful antioxidant and has been used in treatment of infections; however, its role as an adjunctive treatment in CAP is unclear. This review aims to assess the efficacy and safety of vitamin C in adults who require hospitalisation for CAP.METHODS AND ANALYSES:Searches will be conducted from inception to November 2023 on Ovid MEDLINE Daily and MEDLINE, Embase CINAHL, the Cochrane Central Register of Controlled Trials, Scopus, Web of Science and ClinicalTrials.gov databases with the aid of a medical librarian. We will include data from randomised controlled trials reporting vitamin C supplementation in patients with CAP requiring hospitalisation. Two independent reviewers will select studies, extract data and will assess the risk of bias by use of the Risk of Bias tool. The overall certainty of evidence will be assessed by use of the Grading of Recommendations Assessment, Development and Evaluation framework. Random-effects meta-analyses will be conducted, and effect measures will be reported as relative risks with 95% CIs.ETHICS AND DISSEMINATION:No previous ethical approval is required for this review. The findings of this review will be submitted to a scientific journal and presented at an international medical conference.PROSPERO REGISTRATION NUMBER:483860.

Background: Comprehensive resuscitation plans document treatment recommendations, such as ‘Not for cardiopulmonary resuscitation’. When created early in admission as a shared decision-making process, these plans support patient autonomy and guide future treatment. The characteristics of patients who have resuscitation plans documented, their timing, and associations with clinical outcomes remain unclear. Objectives: To characterise factors associated with resuscitation plan completion, early completion, and differences in mortality rates and Intensive Care Unit (ICU) admissions based on resuscitation plan status. Methods: This retrospective study analysed non-elective admissions to an Australian tertiary centre from January to June 2021, examining plan completion timing (early < 48 h, late > 48 h) and associations with mortality and ICU admission. Results: Of 13,718 admissions, 5745 (42%) had a resuscitation plan recorded. Most plans (89%) were completed early. Furthermore, 9% of patients died during admission, and 8.2% were admitted to the ICU. For those without resuscitation plans, 0.5% died (p < 0.001), and 9.7% were admitted to the ICU (p = 0.002). Factors associated with plan completion included a medical unit, in-hours admission, older age, female gender, limited English proficiency, and non-Indigenous status. Plans completed late (>48 h) correlated with a higher mortality (14% vs. 9%; p < 0.001) and more ICU admissions (25% vs. 6%; p < 0.001). Aboriginal and/or Torres Strait Islander patients were often overlooked for resuscitation documentation before death. No resuscitation plans were documented for 62% of ICU admissions. Conclusions: Important disparities exist in resuscitation plan completion rates across highly relevant inpatient and demographic groups.

BACKGROUND:Community-acquired pneumonia (CAP) leads to considerable morbidity and mortality globally. However, data on CAP burden in Australia, especially during the coronavirus disease 2019 (COVID-19) pandemic, are limited. AIMS:We characterised and assessed clinical outcomes of non-COVID-19 CAP hospitalisations over a 6-year period at two major hospitals in South Australia. METHODS:All non-COVID-19 CAP hospitalisations were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth revision, Australian modification (ICD-10-AM) codes, between 1 January 2018 and 31 December 2023, at two tertiary hospitals in Adelaide. Clinical outcomes included in-hospital and 30-day mortality, length of stay (LOS) in, intensive care unit (ICU) admission and 30-day readmissions. Multilevel regression models were utilised to identify predictors of clinical outcomes. RESULTS:Over the 6-year period, there were 7853 non-COVID-19 CAP hospitalisations, with a temporal increase from 100 per 100 000 population in 2018 to 208 per 100 000 population in 2023 (P < 0.001). The mean (SD) age was 75.1 (17.6) years, and 54.6% were males. The mean age declined over time (P < 0.05), while other characteristics remained stable. Streptococcus pneumoniae was the most commonly identified bacterium (21.8% of cases). In-hospital mortality occurred in 7.8% of patients, with 30-day mortality and readmission rates of 14.3% and 16.9% respectively. LOS declined significantly during the pandemic years; however, mortality remained stable over time. Frailty status, malnutrition and number of comorbidities significantly predicted 30-day mortality and LOS, in addition to pneumonia severity and ICU admission. CONCLUSIONS:There has been an increasing trend of hospitalisations for non-COVID-19 CAP during the COVID-19 pandemic, with a concomitant trend towards shorter LOS and no significant shift in other clinical outcomes.

Objective Community-acquired pneumonia (CAP) is a leading cause of emergency hospitalisations globally and is associated with high readmission rates. Specific score systems developed for all medical conditions such as the HOSPITAL score and the LACE index can also usefully predict CAP readmissions. However, there is limited evidence regarding their performance in the Australian healthcare settings. Methods This multicentre retrospective study analysed adult CAP discharges from two metropolitan hospitals in South Australia between 1 January 2018 and 31 December 2023. Data for determining the HOSPITAL score and the LACE index were derived from electronic medical records. Demographic characteristics of patients readmitted within 30 days were compared with those who were not readmitted. The scores were evaluated for overall performance, discriminatory power and calibration, with discriminatory power assessed using the concordance statistic (C-statistic). Results Over 6 years, 7245 CAP discharges were recorded, with 1329 (18.3%) readmissions within 30 days. The mean (s.d.) age of the cohort was 74.4 (17.8) years. Readmitted patients were more likely to have multiple morbidities and frailty than those not readmitted (P < 0.05). They also had a higher mean number of emergency department presentations and hospital admissions in the previous year and a longer initial hospital stay (P < 0.05). Overall, the mean (s.d.) HOSPITAL score and LACE index were 3.4 (2.1) and 9.3 (3.6), respectively. Among readmissions, 28.4% occurred in patients with a HOSPITAL score >4 (intermediate and high-risk group), while 25.8% occurred in patients in the high-risk LACE category (LACE index > 10). The C-statistic for the HOSPITAL score and LACE index was 0.62 (95% CI 0.61-0.64) and 0.63 (95% CI 0.61-0.65), respectively, with no significant difference in the area under the receiver operating characteristic curves (P > 0.05). Conclusions The predictive abilities of the HOSPITAL score and the LACE index for CAP readmissions are modest and comparable in an Australian setting.

OBJECTIVES:The value of the neutrophil-to-lymphocyte ratio (NLR) in predicting outcomes in patients hospitalised with community-acquired pneumonia (CAP) remains debated. This study evaluated whether NLR independently predicts clinical outcomes and enhances the predictive performance of the CURB-65 score in patients with CAP. METHODS:Data from CAP admissions at two Australian hospitals from 2018 to 2023 were analysed. NLR was calculated using admission neutrophil and lymphocyte counts. Patients were categorised into NLR >12 and NLR ≤12. Multilevel-multivariable regression models, adjusting for age, sex, Charlson index, CURB-65 score, Hospital Frailty Risk Score (HFRS) and C-reactive protein (CRP), assessed outcomes including length of stay (LOS), intensive care unit (ICU) admission and in-hospital mortality. RESULTS:Over 6 years, 7,862 patients with CAP were hospitalised (mean age 75.1 years, 54.6% male). Mean NLR was 12.6, with 2,877 (36.6%) patients having an NLR >12. Those with NLR >12 were older males with higher disease severity and Charlson index (p<0.05). Adjusted analyses showed that NLR >12 was independently associated with prolonged LOS (IRR=1.11, 95% CI 1.08-1.13, p<0.001), increased risk of ICU admission (adjusted odds ratio (aOR) =1.41, 95% confidence interval (CI) 1.06-1.88, p=0.019), and higher in-hospital mortality (aOR=1.27, 95% CI 1.06-1.53, p=0.009). The predictive ability of the CURB-65 score for in-hospital mortality was good (area under the curve (AUC) 0.68, 95% CI 0.66-0.70), while it was modest for the NLR (AUC 0.58, 95% CI 0.56-0.60). Incorporation of NLR to the CURB-65 score did not enhance its predictive ability (AUC 0.69, p>0.05). CONCLUSIONS:NLR independently predicts adverse outcomes in patients hospitalised with CAP but does not improve the predictive performance of the CURB-65 score.

Community-acquired pneumonia (CAP) poses a significant global health challenge, prompting exploration of innovative treatments. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of vitamin C supplementation in adults undergoing treatment for CAP. A comprehensive search of the MEDLINE, Embase, CINAHL, the Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases from inception to 17 November 2023 identified six randomized-controlled-trials (RCTs) meeting inclusion criteria. The primary outcome analysis revealed a non-significant trend towards reduced overall mortality in the vitamin C group compared to controls (RR 0.51; 95% CI 0.24 to 1.09; p = 0.052; I2 = 0; p = 0.65). Sensitivity analysis, excluding corona-virus-disease 2019 (COVID-19) studies and considering the route of vitamin C administration, confirmed this trend. Secondary outcomes, including hospital length-of-stay (LOS), intensive-care-unit (ICU) LOS, and mechanical ventilation, exhibited mixed results. Notably, heterogeneity and publication bias were observed in hospital LOS analysis, necessitating cautious interpretation. Adverse effects were minimal, with isolated incidents of nausea, vomiting, hypotension, and tachycardia reported. This meta-analysis suggests potential benefits of vitamin C supplementation in CAP treatment. However, inconclusive findings and methodological limitations warrants cautious interpretation, emphasising the urgency for high-quality trials to elucidate the true impact of vitamin C supplementation in CAP management.

Context Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined.Objective To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma.Design Cross-sectional study.Patients Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma.Methods Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal.Main outcome measure The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma.Results The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS.Conclusion Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality.

Objectives Persistent and significant swallowing impairment can occur in individuals with dementia. Determining prognosis and establishing realistic goals of care in this population is complex and comfort feeding may be recommended. This study aimed to establish evidence relating to patient outcomes following recommendation of comfort feeding to aid informed decision making. Design A multi-centre, retrospective audit was conducted for a two-year period to establish the survival and readmission rates for hospitalised people with dementia, following recommendation of a comfort feeding plan. Setting The study was conducted at three acute care hospitals in Adelaide, South Australia. Participants A total of 163 participants were included, 90 male and 73 female, with a median age of 88 years. Measurements Mortality within 30 and 90 days of admission and readmission rates within 30 days of discharge were calculated. Results Forty-two percent of participants died during the admission during which a comfort feeding plan was recommended. Overall median survival time and one month survival was 13 days and 25%, respectively. Readmission rates were low (7.4% of those discharged). Comfort feeding recommendations aligned with dysphagia severity and those for whom Nil By Mouth (NBM) or ice chips only were recommended were at highest risk of dying in hospital, those recommended thickened fluids +/− ice chips were most likely to be alive 30 days after their original admission date. Conclusion Dementia and comfort feeding were associated with high mortality rates, high rates of discharge to a supportive care facility and low readmission rates. Dysphagia severity associated with the consistency of fluids recommended.

ObjectivePatients admitted from the emergency department may be co-located on the treating team's 'home ward'. If no bed is available, patients may be sent to another ward, where they may remain under the admitting team as an 'outlier'. Conversely, care may be handed over to the team on whose home ward they are located. We conducted a retrospective analysis to understand the impact of outlier status and handovers of care on outcomes for General Medicine inpatients.MethodsGeneral Medicine admissions at the Royal Adelaide Hospital between September 2020 and November 2021 were analysed. We examined the rate of hospital-acquired complications, inpatient mortality rate, mortality within 48 h of admission, Relative Stay Index, time of discharge from hospital and rate of adverse events within 28 days of discharge.ResultsA total of 3109 admissions were analysed. Handovers within 24 h of admission were associated with a longer length of stay. There was a trend towards higher rates of adverse events within 28 days of discharge with handovers of care. Outlier status did not affect any outcome measures.ConclusionsHandovers within the first 24 h of admission are associated with longer than expected length of stay.

Aims: The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia. Methods: In this prospective study, fifty adult inpatients who were taking prednisolone >= 20 mg/day and expe-rienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed. Results: The participants age was 69 +/- 10 years, daily prednisolone dose was 34 +/- 10 mg, HbA1c was 7.7 +/- 2.0 % (61 +/- 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r2 = 0.11, p = 0.024). A multivariate model comprising sex, HbA1c, a prior diagnosis of diabetes, diabetes treatment and weight explained nearly-two thirds of the variability in daily insulin dose (r2 = 0.65, p < 0.001). Conclusions: In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing.

The evidence is strong in favor of blood pressure (BP) control in robust older people as a way to reduce morbidity and mortality in the same way that treatment improves the lives of middle-aged people. Expert editorials have been written over the last five decades persuasively arguing for or against more intensive treatment of older people with hypertension, supported by the specificity of (then) contemporaneous randomized controlled trials (RCTs) or the generalizability of observational studies. But there are limitations.First, there has always been such a thing as too low. Early epidemiological studies showed an upward inflection in mortality curves that resemble a slanted letter J. Second, certain complex older people encountered routinely in a clinic, pharmacy, or nursing facility were often excluded from the RCTs showing benefit from intensive BP control. Cohort studies of these complex people showed a different truth, that the point of "too low" might move up and that BP targets for adults might be too low for select older people. Not all older people are the same. Some are burdened by frailty superimposed on cardiovascular disease and a limited life-expectancy. It is one thing not to start BP-lowering medications for this patient; it is an entirely different matter to stop.

The problem of polypharmacy is complex, pervasive, and expanding. Appropriate prescribing of antihypertensive therapy for older people might help reduce medication burden, but it begins with a better understanding of what the evidence offers and where the evidence is quiet.In the first of this three-part series on antihypertensive medications for older people, we will trace the history of treating blood pressure with medication, from the expert opinion opposing treatment, to the observational data that led to paradigm shifts. We will follow the trail of evidence to randomized controlled trials (RCT) demonstrating the clear benefit of better control of blood pressure for all adults, regardless of age.RCT first evaluated any treatment against placebo, then began comparing one medication with another, and finally, more intensive control compared with less intensive control. Eventually professional societies bundled the evidence into guidelines to help busy prescribers and pharmacists wisely advise the consumers at the coal-face.In this first part of this series, we will present the evidence that favors intensive therapy in older people, that lower is better. In the second part, we will present evidence that highlights the dangers of going too low, and that stopping blood pressure-lowering medication might help. In the third part, we will discuss the evidence, new and old, that shows what happens when you stop.

What happens when you stop? This is the third of a three-part series on antihypertensive medication use in older people. In the first, we reviewed the importance of better blood pressure (BP) control, even in older people with hypertension. In the second, we discussed the limitations of the evidence favoring intensive therapy for some older people. For older people with advanced frailty or those with a limited life expectancy, medications taken for BP can actually be a source of morbidity. Guidelines encourage clinical judgment and rational prescribing. Sometimes the best action is to stop prescribing. De-prescribing of medical therapy is now considered good practice for a range of medications for suitable patients; should this include antihypertensives? In part three of this three-part series, we will review some of the evidence available thus far, demonstrating de-intensification of antihypertensive medications is not a new idea. We will offer a guide to identifying the most suitable patients for de-prescribing: cognitive impairment, frailty, when circumstances change, or when BP is (too) well-controlled. This is an area of equipoise and needs more research. There is a path forward that we hope to illuminate.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce elevated blood glucose levels and induce weight loss. Multiple GLP-1 RAs and one combined GLP-1/glucose-dependent insulinotropic polypeptide agonist are currently available. This review was conducted with the aim of summarising direct comparisons between subcutaneous semaglutide and other GLP-1 RAs in individuals with type 2 diabetes (T2D), particularly with respect to efficacy for inducing weight loss and improving other markers of metabolic health. This systematic review of PubMed and Embase from inception to early 2022 was registered on PROSPERO and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Of the 740 records identified in the search, five studies fulfilled the inclusion criteria. Comparators included liraglutide, exenatide, dulaglutide and tirzepatide. In the identified studies, multiple dosing regimens were utilised for semaglutide. Randomised trials support the superior efficacy of semaglutide over other GLP-1 RAs with respect to weight loss in T2D, but tirzepatide is more effective than semaglutide.