The epidemiology of rapid response team activation amongst patients undergoing major gastrointestinal surgery.

BACKGROUND: Clinical deterioration requiring rapid response team (RRT) review is associated with increased morbidity amongst hospitalised patients. The frequency of and association with RRT calls in patients undergoing major gastrointestinal surgery is unknown. Understanding the epidemiology of RRT calls might identify areas for quality improvement in this cohort. OBJECTIVES: The objective of this study is to identify perioperative risks and outcome associations with RRT review following major gastrointestinal surgery. METHODS: We conducted a retrospective cohort study using electronic databases at a large Australian university hospital. We included adult patients admitted for major gastrointestinal surgery between 1 January 2015 and 31 March 2018. RESULTS: Of 7158 patients, 514 (7.4%) required RRT activation postoperatively. After adjustment, variables associated with RRT activation included the following: hemiplegia/paraplegia (odds ratio [OR]: 8.0, 95% confidence interval [CI]: 2.3 to 27.8, p = 0.001), heart failure (OR: 6.9, 95% CI: 3.3 to 14.6, p < 0.001), peripheral vascular disease (OR: 5.3, 95% CI: 2.7 to 10.4, p < 0.001), peptic ulcer disease (OR: 4.2, 95% CI: 2.2 to 8.0, p < 0.001), chronic obstructive pulmonary disease (OR: 4.0, 95% CI: 2.2 to 7.2, p < 0.001), and emergency admission status (OR: 2.6, 95% CI: 2.1 to 3.3, p < 0.001). Following the index operation, 46% of first RRT activations occurred within 24 h of surgery and 61% had occurred within 48 h. The most common triggers for RRT activation were tachycardia, hypotension, and tachypnoea. Postoperative RRT activation was associated with in-hospital mortality (OR: 6.7, 95% CI: 3.8 to 11.8, p < 0.001), critical care admission (incidence rate ratio: 8.18, 95% CI: 5.23 to 12.77, p < 0.001), and longer median length of hospital stay (12 days vs. 2 days, p < 0.001) compared to no RRT activation. CONCLUSION: After major gastrointestinal surgery, one in 14 patients had an RRT activation, almost half within 24 h of surgery. Such activation was independently associated with increased morbidity and mortality. Identified associations may guide more pre-emptive management for those at an increased risk of RRT activation.

Poor adherence and persistence to sodium glucose co-transporter 2 inhibitors in real-world settings: Evidence from a systematic review and meta-analysis.

AIMS: Despite increasing prescription of sodium glucose co-transporter 2 (SGLT2) inhibitors, there is limited insight of the patterns of use among patients with diabetes prescribed these drugs. This study aimed to summarize available real-world data on the adherence and persistence to SGLT2 inhibitors. MATERIALS AND METHODS: A systematic review for observational studies reporting the adherence and persistence to SGLT2 inhibitors was performed in Medline, Embase, and Web of Science from their inception to October 2019. Data were analysed via random-effects meta-analysis. RESULTS: A total of 22 studies (31 cohorts) comprising 123 854 individuals prescribed SGLT2 inhibitors from eight countries were included. The pooled mean proportions of days covered [PDC] at six months and one year were 0.77 (95% confidence interval [CI] 0.72-0.82) and 0.72 (95% CI 0.66-0.77), respectively. The pooled proportions adherent (PDC ≥0.80) at six months and one year were 59.5% (95% CI 52.9-65.9) and 49.0% (95% CI 42.3-55.8), respectively. The pooled proportions of people persistent at six months, one year, and two years were 80.1% (95% CI 75.8-84.0), 61.8% (95% CI 57.8-65.7), and 45.9% (95% CI 35.5-56.5), respectively. When persistence was defined as the absence of ≥90-days gap, the equivalent pooled proportions persistent were 81.5% (95% CI 73.1-88.6), 58.9% (95% CI 53.1-64.6), and 34.7% (95% CI 33.6-35.8). Adherence and persistence appeared to vary across different SGLT2 inhibitors. CONCLUSIONS: Real-world adherence and persistence to SGLT2 inhibitors is poor. Hence, targets for improving treatment adherence and persistence need to be identified and appropriate interventions implemented.

Impact of tobacco use on health and work productivity in Malaysia.

BACKGROUND: The loss of productivity arising from tobacco use in low/middle-income countries has not been well described. We sought to examine the impact of cigarette smoking on population health and work productivity in Malaysia using a recently published measure, the productivity-adjusted life year (PALY). METHODS: A life table model was constructed using published Malaysian demographic and mortality data. Our analysis was limited to male smokers due to the low smoking prevalence in females (1.1%). Male smokers aged 15-64 years were followed up until 65 years or until death. The population attributable risk, health-related quality of life decrements and relative reduction in productivity due to smoking were sourced from published data. The analysis was repeated assuming the cohorts were never smokers, and the differences in outcomes represented the health and productivity burden conferred by smoking. The cost of productivity loss was estimated based on the gross domestic product per equivalent full-time worker in Malaysia. RESULTS: Tobacco use is highly prevalent among working-age males in Malaysia, with 4.2 million (37.5%) daily smokers among men aged between 15 and 64 years. Overall, our model estimated that smoking resulted in the loss of over 2.1 million life years (2.9%), 5.5 million (8.2%) quality-adjusted life years (QALYs) and 3.0 million (4.8%) PALYs. Smoking was estimated to incur RM275.3 billion (US$69.4 billion) in loss of productivity. CONCLUSION: Tobacco use imposes a significant public health and economic burden among working-age males in Malaysia. This study highlights the need of effective public health interventions to reduce tobacco use.

Cost-Effectiveness of Switching Patients With Heart Failure and Reduced Ejection Fraction to Sacubitril/Valsartan: The Australian Perspective.

BACKGROUND: The cost-effectiveness, from the Australian health care perspective, of switching patients with heart failure and reduced ejection fraction (HFREF) stable on angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) to the angiotensin receptor neprilysin inhibitor (ARNi) sacubitril/valsartan is unclear. We sought to assess the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with HFREF in the contemporary Australian setting. METHODS: We developed a Markov model with two health states ('Alive' and 'Dead') to assess the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with HFREF. Model subjects were 63 years of age at entry and had simulated follow-up over 20 years. Transition probabilities were derived from the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) study. Costs and utility data were derived from published sources. All costs and effects were discounted at an annual rate of 5% and are presented in Australian dollars. Sensitivity analyses were undertaken to test variability in key data inputs. RESULTS: In the base-case analysis, sacubitril/valsartan was found to reduce non-fatal heart failure hospitalisations and cardiovascular deaths, with numbers-needed-to-treat over a 20-year period of 40 and 27, respectively. The use of sacubitril/valsartan led to an additional 6 months of life gained per patient, translating to A$27,954 per years of life saved (YoLS) and A$40,513 per quality-adjusted-life-years (QALY) gained. The results of the sensitivity analyses indicated that the results were robust. CONCLUSIONS: Our analysis supports switching HFREF patients on ACE inhibitor or ARB to sacubitril/valsartan.

Temporal Changes in Characteristics, Treatment and Outcomes of Heart Failure Patients Undergoing Percutaneous Coronary Intervention Findings From Melbourne Interventional Group Registry.

BACKGROUND: Limited data exist on whether outcomes of patients with heart failure (HF) undergoing percutaneous coronary intervention (PCI) have improved over time. The purpose of this study was to assess temporal trends in patient characteristics, treatment and outcomes of patients with HF undergoing PCI. METHODS: Using data from the Melbourne Interventional Group (MIG), we evaluated temporal trends of procedure volume, major adverse cardiac events (MACE; a composite of all-cause mortality, myocardial infarction and target vessel revascularisation) and rates of cardiovascular readmission, all-cause death and cardiovascular death in consecutive patients with HF undergoing PCI. Change over time was assessed by Box-Jenkins autoregressive integrated moving average (ARIMA) models. RESULTS: Data from 1,604 patients were analysed. In our cohort, there were no significant changes in the number of procedures performed annually and patient characteristics between January 2005 and December 2014. Optimal use of HF therapy has improved over the study period. Planned clopidogrel therapy of more than 12 months increased in tandem with increasing use of drug-eluting stents (DES). Procedural success was high (≥90%). However, the rates of MACE, cardiovascular readmission, all-cause death and cardiovascular death remained unchanged throughout the study period. CONCLUSIONS: Clinical outcomes in HF patients undergoing PCI have remained unchanged despite improvement in medical technology and contemporary therapeutic measures.

Mind the Gap: Mismatches Between Clinicians and Patients in Heart Failure Medication Management.

PURPOSE: Previous studies on the 'treatment gap' in patients with heart failure (HF) have focused either on prescribing or patients' adherence to prescribed treatment. This study sought to determine whether or not recent initiatives to close the gap have also minimised any mismatches between physicians' expectation of their patients' medications, medications in the patients' possession and their actual medication use. METHODS: A cross-sectional observational survey was conducted from December 2015 to June 2016 in The Alfred Hospital HF clinic in Melbourne, Australia. Patients were invited to participate if they had chronic HF (NYHA class II to IV), were aged ≥ 60 years, had no history of HF related hospitalisation within the past 6 months and were prescribed at least two HF medications. RESULTS: Of 123 eligible patients, 102 were recruited into the study. Beta-blockers, mineralocorticoid receptor antagonists, loop diuretics and statins were associated with the highest rates of mismatches of drugs and doses, ranging from 10 to 17%. Discrepancy of total daily doses was the most common type of mismatch. Overall, only 23.5% of the patients were taking the right drugs at the right doses as expected by their cardiologists/HF specialists. CONCLUSIONS: Despite improved prescribers' adherence to guideline-directed medical therapy, there remain considerable mismatches between prescribers' expectation of patients' HF medications, medications in patients' possession and their actual medication use. Initiatives to improve this situation are urgently needed.

Does Statin Benefits Patients with Heart Failure Undergoing Percutaneous Coronary Intervention? Findings from the Melbourne Interventional Group Registry.

PURPOSE: The effectiveness of statins in improving clinical outcomes among patients with heart failure (HF) undergoing percutaneous coronary intervention (PCI) is unclear. We examined the association between use of statins and clinical outcomes in patients with HF included in the Melbourne Interventional Group registry. METHODS: Patients were followed from 30 days to 1 year post-PCI for a primary composite outcome of all-cause mortality and hospitalisation for cardiovascular (CV) causes. Secondary outcomes included major adverse cardiac events (MACE, a composite of all-cause mortality, myocardial infarction and target vessel revascularisation) and hospitalisation for CV causes. Outcomes were compared between statin-treated and non-statin-treated patients (at 30 days post-PCI) using propensity scores to balance for risk factors. RESULTS: Among 991 patients included in the inverse probability-weighted Cox model, statin use had no significant effect on the primary composite outcome [adjusted hazard ratio (aHR), 1.03; 95% confidence interval (CI), 0.68 to 1.56; p = 0.89], nor MACE (aHR, 0.99; 95% CI, 0.54 to 1.84; p = 0.99) or hospitalisation for CV causes (HR, 1.13; 95% CI, 0.74 to 1.72; p = 0.57). CONCLUSIONS: Our results suggest that statin therapy may confer no significant benefits in patients with HF undergoing PCI. However, prospective randomised controlled trials are needed to provide more definitive answers.

Risk Prediction Models for Incident Heart Failure: A Systematic Review of Methodology and Model Performance.

BACKGROUND: Numerous models predicting the risk of incident heart failure (HF) have been developed; however, evidence of their methodological rigor and reporting remains unclear. This study critically appraises the methods underpinning incident HF risk prediction models. METHODS AND RESULTS: EMBASE and PubMed were searched for articles published between 1990 and June 2016 that reported at least 1 multivariable model for prediction of HF. Model development information, including study design, variable coding, missing data, and predictor selection, was extracted. Nineteen studies reporting 40 risk prediction models were included. Existing models have acceptable discriminative ability (C-statistics > 0.70), although only 6 models were externally validated. Candidate variable selection was based on statistical significance from a univariate screening in 11 models, whereas it was unclear in 12 models. Continuous predictors were retained in 16 models, whereas it was unclear how continuous variables were handled in 16 models. Missing values were excluded in 19 of 23 models that reported missing data, and the number of events per variable was < 10 in 13 models. Only 2 models presented recommended regression equations. There was significant heterogeneity in discriminative ability of models with respect to age (P < .001) and sample size (P = .007). CONCLUSIONS: There is an abundance of HF risk prediction models that had sufficient discriminative ability, although few are externally validated. Methods not recommended for the conduct and reporting of risk prediction modeling were frequently used, and resulting algorithms should be applied with caution.

The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice.

The extent and impact of under-prescribing of evidence-based pharmacological therapies among heart failure patients with reduced ejection fraction (HFREF) in contemporary practice is unclear. We sought to examine the prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), ß-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs), and to quantify the estimated 'treatment gap' among HFREF patients in the 'real-world' setting. The MEDLINE, PubMed, EMBASE, CINAHL and CENTRAL databases were searched for registry- or survey-based studies which examined the prescribing rates of ACE inhibitors, ARBs, BBs and MRAs among HFREF patients. Searches were limited to those published in the years 2000-2015. A total of 23 reports, including 83,605 patients, were evaluated. Overall, ACE inhibitors/ARBs, BBs and MRAs were prescribed to 79.8, 81.4 and 36.4 % of patients, respectively. The estimated treatment gaps in the overall population were 13.1 % for ACE inhibitors/ARBs, 3.9 % for BBs and 16.8 % for MRAs. The proportion of patients who received ≥50 % of the guideline-recommended target doses was 72 % for ACE inhibitors, 51 % for ARBs, 49 % for BBs, 53 % for the combination of ACE inhibitors/ARBs and BBs and 83 % for MRAs. Prescribing these drugs according to contemporary guidelines was associated with lower mortality risk. Patients who were elderly, female and with comorbidities were less likely to receive optimal treatment as recommended by the guidelines. ACE inhibitors, ARBs, BBs and MRAs are under-prescribed in eligible HFREF patients. Efforts should be made to improve approaches to closing the treatment gap at both systems of care and individual levels.

Comorbidities in Heart Failure: Are There Gender Differences?

Compared to men, women with heart failure (HF) are often older, smoke less, and have more preserved ejection fraction (EF) and hypertensive HF rather than HF of ischemic etiology. Gender-stratified outcomes on comorbidities data in HF are scarce. Women have traditionally been underrepresented in HF trials. Although data suggest that overall prognosis may be better in women, they experience lower quality of life with greater functional impairment from HF compared to men. Gender differences have been reported for comorbid diabetes, chronic obstructive pulmonary disease, renal dysfunction, anemia, and depression and may explain gender disparity in outcomes. However, possible confounding of comorbidities with known prognostic determinants in HF (such as EF) as well as gender differences in the utilization of medical therapies obscures interpretation. In this review, we will explore the evidence for gender differences in non-cardiovascular comorbidities in HF. Our findings may guide clinicians to individualize HF care, according to best practice, in the hope of improving prognosis for this chronic and debilitating condition.

Is Hepatocellular Carcinoma in Fatty Liver Different to Non-Fatty Liver?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in Australia and is recognised to play a role in the development of hepatocellular carcinoma (HCC). There are no clear guidelines regarding screening for HCC in NAFLD. The aim of this retrospective study was to compare the characteristics and survival rates of NAFLD-HCC to patients with non-NAFLD-HCC to help guide future research in this area. METHODS: A total of 152 HCC patients with either NAFLD (n = 36) or non-NAFLD (n = 116) were retrospectively analysed from the HCC database and medical records. Chi-square and independent t-test were used to compare baseline characteristics and Kaplan-Meier curves and Cox models were used for survival analysis. RESULTS: Patients with NAFLD-HCC were more likely to be diagnosed due to symptoms rather than through screening, and at an older age, compared with non-NAFLD HCC. The median survival rates were lower in NAFLD-HCC (17.2 months) than in those with non-NAFLD-HCC (23.5 months). CONCLUSION: There is a rise in the number of HCC cases in patients with NAFLD, and this has significant implications for hepatologists as they are presented with more advanced diseases and have poorer outcomes. Future studies on HCC will need to identify this group earlier in order to have an impact on the HCC survival rate.

Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis involving 594,138 patients with type 2 diabetes.

AIMS: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. METHODS: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. RESULTS: Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3-64.4) at one year and 44.2% (95% CI 36.4-52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5-79.5) at six months to 52.8% (95% CI 51.6-59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1-3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. CONCLUSIONS: Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

A retrospective case-controlled cohort study of inpatient drug induced liver injury: the RIDDLE study.

BACKGROUND: Identification of risk factors for drug-induced liver injury (DILI) has been hindered by the unpredictable incidence and idiosyncratic nature of DILI. The aim of this study was to identify characteristic host risk factors for DILI. METHODS: A retrospective cohort study was performed examining all patients admitted with a diagnosis of DILI over a 5.5-year period. Cases were compared to a control group non-exposed to DILI using propensity score-derived inverse probability weights. Patients with DILI due to alcohol or paracetamol were excluded from analysis. RESULTS: Seventy-two cases of DILI admitted to hospital were identified. Antimicrobials caused 56.9% of cases, with amoxicillin-clavulanate the single most common agent, responsible for 13.9% of cases. DILI cohort median age (50.2±36 years) was significantly younger than controls (65.0±38 years) (P<0.001). Pre-existing chronic liver disease (OR, 3.44; 95% CI, 1.38-8.59; P=0.008), length of stay (P<0.001) and in-hospital death (P=0.009) were more likely to be associated with DILI cases. There was no correlation with sex (OR male, 0.92; 95% CI, 0.50-1.67; P=0.78), presence of comorbid autoimmune disease (OR, 1.44; 95% CI, 0.68-3.05; P=0.35), past drug allergies (OR, 1.71; 95% CI, 0.92-3.16; P=0.09), or atopy (OR, 0.87; 95% CI, 0.42-1.82; P=0.72). CONCLUSIONS: Younger age and presence of chronic liver disease were associated with an admission with DILI; however, it remains difficult to predict the population at risk of DILI on clinical grounds and putative risk factors such as female gender, and history of other drug allergies and autoimmunity, were not demonstrated in this study.

Retrospective study of idiosyncratic drug-induced liver injury from infliximab in an inflammatory bowel disease cohort: the IDLE study.

BACKGROUND: Infliximab therapy may be associated with drug-induced liver injury (DILI), often resembling a drug-induced autoimmune hepatitis. However, the prevalence of DILI in patients receiving infliximab is unclear. Abnormal liver biochemistry is common in patients with inflammatory bowel disease (IBD) and definitive diagnosis may be difficult. The aim of this study was to describe the patterns of abnormal liver biochemistry in an IBD cohort. METHODS: In a retrospective cohort study of adult patients with IBD treated with infliximab through a single institution we used the Roussel Uclaf Causality Assessment Method (RUCAM) to evaluate liver biochemistry and possible DILI. All cases of abnormal liver biochemistry were ascribed a presumptive diagnosis from the electronic medical record. RESULTS: Fifty-seven of the 175 patients (149 Crohn's disease, 26 ulcerative colitis) had abnormal liver biochemistry. Of the 57 cases, one had highly probable, and 10 possible DILI due to infliximab. There were no significant differences regarding demographics, concomitant therapy/disease, indication for infliximab or outcomes between patients with normal and abnormal liver biochemistry, except for higher baseline alanine transaminase and alkaline phosphatase in the abnormal biochemistry group (P<0.001). Multivariate logistic regression showed male sex (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.22-5.09; P=0.01) and background liver disease (OR 15.09, 95%CI 4.09-55.69; P<0.001) to be associated with the abnormal liver biochemistry group. CONCLUSIONS: Abnormal liver biochemistry is common in IBD patients on infliximab. Patients who are male, or have abnormal pre-therapy liver biochemistry or background liver disease, are more likely to develop worsening liver biochemistry during infliximab therapy. RUCAM scoring may help identify true cases of DILI.

Trends in the Dispensing and Costs of Glucose-Lowering Medications Among Older Australians: Findings from National Claims Data.

BACKGROUND: Temporal changes in the dispensing of glucose-lowering drugs (GLD) and their associated costs among elderly populations is unclear. This information is especially relevant to countries in which medications are partly or fully government subsidized. OBJECTIVE: Our objective was to estimate the trends in prevalence, incidence and costs associated with GLD dispensed to older Australians. METHODS: We analysed Pharmaceutical Benefits Scheme data for 76,906 people aged ≥ 65 years dispensed diabetes medications over the period 2013-2016. RESULTS: Older males were dispensed more GLD than were older females, with the marginal difference increasing from 3.2% in 2013 (age-sex adjusted incidence rate ratio [aIRR] 1.032; 95% confidence interval [CI] 1.024-1.041; p < 0.001) to 3.9% in 2016 (aIRR 1.039; 95% CI 1.030-1.047; p < 0.001). The number of GLD dispensed per person was consistently lower in those aged ≥ 75 years than in those aged 65-74 years, with the gap widening over the years. More patients were initiated with sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors over the study period, at the expense of older GLD. The proportion of users and attributed costs associated with the use of metformin, sulfonylureas, α-glucosidase inhibitors and thiazolidinediones decreased over time. The total subsidized costs of GLD is forecast to increase to $A395 million by 2020. CONCLUSIONS: The treatment landscape for diabetes in Australia is undergoing dynamic change. More patients were initiated with the newer but costlier GLD over the study period.

Cancer is associated with severe disease in COVID-19 patients: a systematic review and meta-analysis.

Cancer patients are vulnerable to complications of respiratory viruses. This systematic review and meta-analysis sought to examine the prevalence of cancer and its association with disease severity in patients with novel coronavirus disease 2019 (COVID-19). Searches were performed in MEDLINE, EMBASE and ScienceDirect from their inception until 28 April 2020. Severe disease was considered to encompass cases resulting in death or as defined by the primary study authors. Meta-analysis was performed using random-effect models. We included 20 studies involving 32,404 patients from China, the United Kingdom, the United States, Italy, Singapore, Thailand, France, India and South Korea. The pooled prevalence of cancer was 3.50% (95% confidence interval (CI) 1.70 to 5.80). The pooled prevalence was not moderated by study mean age, proportion of females or whether the study was conducted in/outside of China. Patients with cancer were more likely to experience severe COVID-19 disease compared to patients without cancer (pooled risk ratio 1.76, 95% CI 1.39 to 2.23). Our findings reiterate the need for additional precautionary measures to ensure that patients with cancer are not exposed to COVID-19, and if they become infected, extra attention should be provided to minimise their risk of adverse outcomes.

Frailty Confers High Mortality Risk across Different Populations: Evidence from an Overview of Systematic Reviews and Meta-Analyses.

We performed an overview of systematic reviews and meta-analyses to summarize available data regarding the association between frailty and all-cause mortality. Medline, Embase, CINAHL, Web of Science, PsycINFO, and AMED (Allied and Complementary Medicine) databases were searched until February 2020 for meta-analyses examining the association between frailty and all-cause mortality. The AMSTAR2 checklist was used to evaluate methodological quality. Frailty exposure and the risk of all-cause mortality (hazard ratio [HR] or relative risk [RR]) were displayed in forest plots. We included 25 meta-analyses that pooled data from between 3 and 20 studies. The number of participants included in these meta-analyses ranged between <2000 and >500,000. Overall, 56%, 32%, and 12% of studies were rated as of moderate, low, and critically low quality, respectively. Frailty was associated with increased risk of all-cause mortality in 24/24 studies where the HR/RRs ranged from 1.35 [95% confidence interval (CI) 1.05-1.74] (patients with diabetes) to 7.95 [95% CI 4.88-12.96] (hospitalized patients). The median HR/RR across different meta-analyses was 1.98 (interquartile range 1.65-2.67). Pre-frailty was associated with a significantly increased risk of all-cause mortality in 7/7 studies with the HR/RR ranging from 1.09 to 3.65 (median 1.51, IQR 1.38-1.73). These data suggest that interventions to prevent frailty and pre-frailty are needed.

Maternal and neonatal outcomes associated with COVID-19 infection: A systematic review.

BACKGROUND: COVID-19 has created an extraordinary global health crisis. However, with limited understanding of the effects of COVID-19 during pregnancy, clinicians and patients are forced to make uninformed decisions. OBJECTIVES: To systematically evaluate the literature and report the maternal and neonatal outcomes associated with COVID-19. SEARCH STRATEGY: PubMed, MEDLINE, and EMBASE were searched from November 1st, 2019 and March 28th, 2020. SELECTION CRITERIA: Primary studies, reported in English, investigating COVID-19-positive pregnant women and reporting their pregnancy and neonatal outcomes. DATA COLLECTION AND ANALYSIS: Data in relation to clinical presentation, investigation were maternal and neonatal outcomes were extracted and analysed using summary statistics. Hypothesis testing was performed to examine differences in time-to-delivery. Study quality was assessed using the ICROMS tool. MAIN RESULTS: Of 73 identified articles, nine were eligible for inclusion (n = 92). 67.4% (62/92) of women were symptomatic at presentation. RT-PCR was inferior to CT-based diagnosis in 31.7% (26/79) of cases. Maternal mortality rate was 0% and only one patient required intensive care and ventilation. 63.8% (30/47) had preterm births, 61.1% (11/18) fetal distress and 80% (40/50) a Caesarean section. 76.92% (11/13) of neonates required NICU admission and 42.8% (40/50) had a low birth weight. There was one indeterminate case of potential vertical transmission. Mean time-to-delivery was 4.3±3.08 days (n = 12) with no difference in outcomes (p>0.05). CONCLUSIONS: COVID-19-positive pregnant women present with fewer symptoms than the general population and may be RT-PCR negative despite having signs of viral pneumonia. The incidence of preterm births, low birth weight, C-section, NICU admission appear higher than the general population.

Recent Patterns of Multimorbidity Among Older Adults in High-Income Countries.

Population aging along with the rising burden of chronic medical conditions (CMCs) is challenging the sustainability of health care systems globally. The authors sought to characterize contemporary patterns of multimorbidity among older adults (aged ≥65 years) in high-income countries (HICs). Medline, EMBASE, CINAHL, PsycINFO, and Web of Science were searched in January 2018 for English-language articles that reported the prevalence of multimorbidity (defined as co-occurrence of ≥2 CMCs in an individual without defining an index disease) among older adults in HICs, or the proportions with ≥3 or ≥5 CMCs. Only studies that utilized data collected during January 2007-December 2017 were included. A total of 52 articles (45 studies) that reported data among >60 million older adults in 30 HICs were included. The overall prevalence of multimorbidity was 66.1% (interquartile range [IQR] 54.4-76.6). The multimorbidity prevalence increased with age as well as with the number of CMCs included in the assessment. The prevalence of ≥3 or ≥5 CMCs was 44.2% (IQR 34.0-70.3) and 12.3% (IQR 8.7-19.1), respectively. The multimorbidity prevalence was also higher among females as well as among studies using care-based data rather than self-reported data. The prevalence of hypertension, dyslipidemia, diabetes, pain disorders, depression, heart failure, cancer, and dementia among the older adults was 60.6%, 51.2%, 25.2%, 34.0%, 12.0%, 14.0%, 8.6%, and 8.4%, respectively. The available data suggest a high prevalence of multimorbidity among older adults. There is a need for increased research into understanding the causal mechanisms that underlie multimorbidity toward supporting the development of cost-effective interventions. In addition, the study results reiterate the need for preventive health care to move beyond targeting single diseases in favor of directing efforts toward reducing overall morbidity among this population.

Cost-effectiveness of first-line versus delayed use of combination dapagliflozin and metformin in patients with type 2 diabetes.

The present study sought to evaluate the cost-effectiveness of first-line (immediate) versus delayed use of combination dapagliflozin and metformin in patients with type 2 diabetes, from the perspective of the Australian healthcare system. We developed a Markov model to simulate the progress of subjects with type 2 diabetes. Decision analysis was applied to assess the cost-effectiveness of first-line combination dapagliflozin and metformin versus first-line metformin monotherapy followed by gradual addition of dapagliflozin over time. Transition probabilities, costs (in Australian dollars) and utility data were derived from published sources. All costs, years of life lived and quality adjusted life years (QALYs) lived were discounted at an annual rate of 5%. Over a 20-year model period, first-line use of combination dapagliflozin and metformin was predicted to reduce the onset of hospitalisation of heart failure, cardiovascular deaths and all cause deaths by 5.5%, 57.6% and 29.6%, respectively. An additional 2.5 years of life (discounted) and 1.9 QALYs (discounted) would be gained per patient, at a cost of AUD $23,367 (discounted) per person. These figures equated to AUD $9,535 per years of life saved (YoLS) and AUD $12,477 per QALYs saved. Sensitivity analyses indicated the results to be robust. Compared to first-line metformin monotherapy followed by gradual addition of dapagliflozin, first-line use of combination dapagliflozin and metformin is likely to be a cost-effective approach to the management of Australians with type 2 diabetes mellitus.