Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality

Background: Conflicting findings and the analysis of unpublished and retracted data have led to controversy on the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in people with COVID-19 infection. This meta-analysis examined the association of prescription of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) with the outcome from COVID-19. Methods: A systematic search was conducted to find published studies that reported the outcome of COVID-19 in relation to prescription of ACEI or ARB. Two authors (MF and AD) independently screened and extracted data and assessed study quality and strength of association using standardised tools. The endpoints for the meta-analyses were severe or critical disease outcome and mortality based on standardised criteria. Results: Twenty-six studies including 8389 people prescribed ACEI or ARB and 20,989 people not prescribed these medications were included. The quality of studies varied, and the overall strength of association was poor with a high risk of confounding bias. Patients prescribed ACEI or ARB had a greater prevalence of risk factors. Meta-analysis found an association between prescription of ACEI or ARB with severe or critical disease outcome (risk ratio, RR, 1.23, 95% confidence interval, CI, 1.06 to 1.42, p = 0.006, I2 = 88%) but this association was lost in sensitivity analyses. There was no association between ACEI or ARB prescription and mortality (RR 1.18, 95% CI 0.92 to 1.50, p = 0.19, I2 = 82%). Conclusions: This meta-analysis suggests that people prescribed ACEI or ARB more commonly had severe or critical disease outcome, but not mortality, in published cohorts of patients diagnosed with COVID-19. This finding is most likely due to a greater prevalence of risk factors in these patients rather than due to exposure to angiotensin pathway inhibitors

Opinions of vascular surgeons and podiatrists in Australia and New Zealand on the use of hyperbaric oxygen therapy for lower limb ulcers

Introduction: Hyperbaric oxygen therapy (HBOT) has been suggested to improve healing of lower limb ulcers, though the quality of available evidence is weak to moderate. This study assessed the opinions and use of HBOT by specialists treating lower limb ulcers. Research design and methods: Accredited vascular surgeons and podiatrists in Australia and New Zealand were sent an online survey via their professional organizations. The survey asked about their use and opinions of HBOT in treating lower limb ischemic, neuropathic and venous ulcers. Data were summarized with descriptive statistics. Non-parametric tests were used to compare survey results obtained from vascular surgeons and podiatrists. Results: 61 vascular surgeons and 40 podiatrists completed the survey. Thirty-seven specialists used HBOT for treating lower limb ulcers, with the remainder indicating they did not feel there was a role for HBOT (n=25) or did not have access to HBOT (n=39). Less than 8% of specialists indicated that HBOT frequently or always had a role in treating ischemic, neuropathic or venous ulcers. Compared with podiatrists, vascular surgeons were significantly less likely to indicate HBOT had a treatment role for any ulcer type (p<0.001, p=0.004, and p<0.001, respectively), though significantly more likely to indicate they currently used HBOT for treating lower limb ulcers (p<0.001). Most specialists (n=76) believed that a large clinical trial is needed to determine the efficacy of HBOT in treating lower limb ulcers. Conclusions: Vascular surgeons and podiatrists do not feel HBOT has a frequent role in treating lower limb ulcers, but do feel there needs to be a large clinical trial to test its value

Effectiveness of Remotely Delivered Interventions to Simultaneously Optimize Management of Hypertension, Hyperglycemia and Dyslipidemia in People With Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Remotely delivered interventions may be more efficient in controlling multiple risk factors in people with diabetes. Purpose: To pool evidence from randomized controlled trials testing remote management interventions to simultaneously control blood pressure, blood glucose and lipids. Data Sources: PubMed/Medline, EMBASE, CINAHL and the Cochrane library were systematically searched for randomized controlled trials (RCTs) until 20th June 2021. Study Selection: Included RCTs were those that reported participant data on blood pressure, blood glucose, and lipid outcomes in response to a remotely delivered intervention. Data Extraction: Three authors extracted data using a predefined template. Primary outcomes were glycated hemoglobin (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), systolic and diastolic blood pressure (SBP & DBP). Risk of bias was assessed using the Cochrane collaboration RoB-2 tool. Meta-analyses are reported as standardized mean difference (SMD) with 95% confidence intervals (95%CI). Data Synthesis: Twenty-seven RCTs reporting on 9100 participants (4581 intervention and 4519 usual care) were included. Components of the remote management interventions tested were identified as patient education, risk factor monitoring, coaching on monitoring, consultations, and pharmacological management. Comparator groups were typically face-to-face usual patient care. Remote management significantly reduced HbA1c (SMD -0.25, 95%CI -0.33 to -0.17, p<0.001), TC (SMD -0.17, 95%CI -0.29 to -0.04, p<0.0001), LDL-c (SMD -0.11, 95%CI -0.19 to -0.03, p=0.006), SBP (SMD -0.11, 95%CI -0.18 to -0.04, p=0.001) and DBP (SMD -0.09, 95%CI -0.16 to -0.02, p=0.02), with low to moderate heterogeneity (I²= 0 to 75). Twelve trials had high risk of bias, 12 had some risk and three were at low risk of bias. Limitations: Heterogeneity and potential publication bias may limit applicability of findings. Conclusions: Remote management significantly improves control of modifiable risk factors

Evolution of WIfI: Expansion of WIfI Notation After Intervention

Nearly a decade ago, the Society for Vascular Surgery (SVS)'s wound, ischemia, and foot Infection (WIfI) classification was first developed to help assess overall limb threat. However, managing conditions such as diabetic foot ulcer and chronic limb-threatening ischemia can be complex. For instance, certain investigative findings might initially be pending such as the level of ischemia or extent of infection before the final classification is established. In addition, wounds evolve rapidly, and the current classification does not allow for tracking their progression over time during treatment. Therefore, we propose a supplemental consistent notation for scoring WifI re-assessment during treatment of a threatened limb inspired by the cancer staging before and after neoadjuvant treatment classification system. Thus, we describe the re-scoring system and how to use it. Our suggestion supports a coherent method to longitudinally communicate characteristics of a threatened limb. This has potential to support high quality interdisciplinary, patient-centered care and enhance the use of this classification in research. Further work is required to validate this modification of a common language of risk

Efficacy of at home monitoring of foot temperature for risk reduction of diabetes-related foot ulcer: A meta-analysis

Aims: To perform an updated systematic review of randomised controlled trials examining the efficacy of at-home foot temperature monitoring in reducing the risk of a diabetes-related foot ulcer (DFU). Methods: Systematic review performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Risk-of-bias was assessed using version 2 of the Cochrane risk-of-bias tool. Meta-analyses were performed using random effect models. Leave-one-out sensitivity analyses and a sub-analysis excluding trials considered at high risk-of-bias assessed the consistency of the findings. The certainty of the evidence was assessed with GRADE. Results: Five randomised controlled trials involving 772 participants meeting the International Working Group on the Diabetic Foot (IWGDF) risk category 2 or 3 were included. All trials reported instructing participants to measure skin temperature at-home at six or more sites on each foot using a hand-held infra-red thermometer at least daily and reduce ambulatory activity in response to hotspots (temperature differences >2.2°C on two consecutive days between similar locations in both feet). One, one, and three trials were considered at low, moderate and high risk-of-bias, respectively. Participants allocated to at-home foot temperature monitoring had a reduced risk of developing a DFU (relative risk 0.51, 95% CI 0.31–0.84) compared to controls. Sensitivity and sub-analyses suggested that the significance of this finding was consistent. The GRADE assessment suggested a low degree of certainty in the finding. Conclusions: At-home daily foot temperature monitoring and reduction of ambulatory activity in response to hotspots reduce the risk of a DFU in moderate or high risk people with a low level of certainty

Current Management of Peripheral Artery Disease: Focus on Pharmacotherapy

Peripheral artery disease (PAD) is the occlusion or narrowing of the arteries supplying the lower extremities. Peripheral artery disease has been estimated to affect approximately 240 million people worldwide, approximately 70% of whom are within low- or middle-income countries. Due to the ageing population and diabetes epidemic, the prevalence of PAD is rapidly rising. The symptoms of PAD are heterogeneous and thus a high index of suspicion is needed to prevent delays in diagnosis and treatment. Measurement of ankle brachial pressure index or arterial duplex ultrasound are traditionally used to diagnose PAD. Patients with PAD have a high risk of major adverse cardiovascular events. Early diagnosis and implementation of secondary cardiovascular prevention is therefore critical. This includes therapies to reduce low-density lipoprotein cholesterol, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, blood-pressure reducing medications and anti-thrombotic drugs. Treatments to facilitate smoking cessation and control blood sugar if relevant and an exercise programme are also critical in reducing cardiovascular risk. Currently, these treatments are not well implemented. This review summarises the clinical presentation, risk factors and medical management of PAD. Global efforts are needed to reduce the burden from the growing PAD epidemic by implementing best practices and improving outcomes through further research

Health Professionals’ Opinions About Secondary Prevention of Diabetes-Related Foot Disease

This study explored health professionals’ perceptions of current issues and opportunities for the secondary prevention of diabetes-related foot disease (DFD), and potential strategies for improving DFD care. From May to October 2020, relevant Australian health professionals completed an online survey which used ordinal scales, ranking questions, and open text fields to assess perceptions about the importance of aspects of secondary prevention for DFD and elements for a prevention program. Quantitative data were summarised and compared between professions using non-parametric tests, and qualitative data was analysed using conceptual content analysis to identify emerging themes. Perceptions from 116 health professionals with experience in managing patients with DFD were obtained, including 69 podiatrists, 21 vascular surgeons, 16 general practitioners, and ten nurses. Access and adherence to appropriate offloading footwear was perceived as a key element for effective DFD care, and believed to be affected by social and economic factors, such as the cost of footwear, as well as patient-related factors, such as motivation to wear footwear and adhere to other medical therapies. In addition to a lack of patient motivation and financial limitations, health professionals also believed patients lacked an understanding of the likelihood and severity of DFD recurrence. Several elements of care were perceived as missing from practice, including psychological support and ways to improve footwear adherence, with health professionals identifying several strategies for the design and implementation of an effective secondary prevention program. Prospective trials evaluating secondary prevention programs are required to determine the most effective means for preventing DFD recurrence

Cytomegalovirus infection in a single-centre Australian neonatal cohort

Aim: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital malformation, non-genetic sensorineural hearing loss and neurodevelopmental sequelae in childhood. The primary aim of this retrospective cohort study was to identify the birth and neurodevelopmental outcomes of neonates diagnosed with symptomatic and asymptomatic cCMV in a large regional tertiary referral hospital. Methods: This was a retrospective cohort study of laboratory-based cCMV diagnoses in neonates born at a single study centre between January 2005 and January 2020. Audit of medical records was undertaken to evaluate maternal characteristics, symptom patterns, radiological and neurodevelopmental outcomes of neonates meeting the laboratory diagnostic criteria during the first 24 months. Results: There were 45 neonates with proven CMV infection and 27 mothers with proven infection with an associated pregnancy outcome. Nineteen neonates were born at term (>37 weeks). Of these, 32 (71.1%) neonates had a significant intercurrent comorbidity and 22 (48.9%) neonates were reported to have a degree of delay in one or more developmental domains. A large proportion (77.3%) of the symptomatic untreated neonates had an unknown history of maternal infection compared to the asymptomatic (10.0%) and symptomatic treated (53.8%) neonates (P = 0.001). Conclusion: Up to half of the neonates with cCMV were at risk of developing a degree of developmental delay at our centre. Whether these outcomes are related primarily to CMV infection or are confounded by the co-existence of prematurity is unclear and needs further evaluation in prospective studies

Health Professionals’ Opinions About Secondary Prevention of Diabetes-Related Foot Disease

Purpose: The purpose of this study was to explore the perceptions of health professionals regarding the ideal design of a remotely delivered diabetes-related foot disease (DFD) secondary prevention program. Methods: A qualitative study involving 33 semistructured phone interviews was conducted with health professionals with experience managing DFD. Interviews discussed the role of health professionals in managing DFD, their experience in using telehealth, perceived management priorities, preferences for a secondary prevention management program, and perceived barriers and facilitators for such a program. Interviews were audio-recorded and transcribed, and inductive thematic analysis was used to derive key themes. Results: Three themes were derived: (1) barriers in current model of DFD care, (2) facilitators and ideas for a remotely delivered secondary prevention program, and (3) potential challenges in implementation. DFD care remains acute-care focused, with variability in access to care and a lack of “clinical ownership.” Patients were perceived as often having poor knowledge and competing priorities, meaning engagement in self-care remains poor. Participants felt a remote secondary prevention program should be simple to follow and individualized to patients’ context, with embedded support from a case manager and local multidisciplinary service providers. Challenges to implementation included limited DFD awareness, poor patient motivation, patient-related issues with accessing and using technology, and the inability to accurately assess and treat the foot over telehealth. Conclusions: Health professionals felt that an ideal remotely delivered secondary prevention program should be tailored to patients’ needs with embedded support from a case manager and complemented with multidisciplinary collaboration with local service providers