A Methodological Assessment of Diabetic Foot Syndrome Clinical Practice Guidelines.

OBJECTIVE: Diabetic foot syndrome (DFS) contributes to significant morbidity in diabetic patients. Diagnostic and therapeutic approaches to DFS may be summarised in clinical practice guidelines (CPGs) to aid clinical practice but may only benefit patients if the CPG is of high quality. This study determines the methodological quality of DFS CPGs using a validated assessment tool to identify CPGs adequate for use in clinical practice. METHODS: Medline, EMBASE, and CPG databases were searched to 31 May 2019. Reference lists were also searched. Full text English evidence based DFS CPGs were included. CPGs based on expert consensus, guideline summaries, or those only available if purchased were excluded. Four reviewers independently assessed methodological quality using the Appraisal of Guidelines for Research and Evaluation II instrument. An overall guideline assessment scaled score of ≥80% was considered to be of adequate quality to recommend use. RESULTS: Sixteen CPGs were identified. Good inter-reviewer reliability (ICC 0.985, 95% CI 0.980-0.989) was achieved. Poor scores were noted in domains 2 (stakeholder involvement), 5 (applicability), and 6 (editorial independence). Significant methodological heterogeneity was observed in all domains with the most noted in domain 6 (mean scaled score 43.2 ± 32.1%). Four CPGs achieved overall assessment scores of ≥80%. CONCLUSION: Four CPGs were considered to be adequate for clinical practice based on methodological quality. However, elements of methodological quality were still lacking, and all CPGs had areas for improvement, potentially through increased multidisciplinary team involvement and trial application of recommendations. Methodological rigour may be improved using structured approaches with validated CPG creation tools in the future. Future work should also assess recommendation accuracy using available validated assessment tools.

A Systematic Review of the Impact of Foot Care Education on Self Efficacy and Self Care in Patients With Diabetes.

OBJECTIVE: This review aims to assess the evidence supporting the impact of patient foot care education on self efficacy, self care behaviour, and self care knowledge in individuals with diabetes. METHODS: This systematic review was registered prospectively on the PROSPERO database (CRD42019106171). Ovid EMBASE and MEDLINE databases were searched from 1946 to the end of March 2019, using search terms related to the domains diabetic foot, patient education, self efficacy, self care behaviour, and self care knowledge. All included studies were prospective, randomised controlled trials that assessed foot care education interventions in individuals with diabetes and recorded an outcome related to self efficacy, self care behaviour, and/or self care knowledge. RESULTS: Thirteen randomised controlled trials were included, reporting on a total of 3948 individuals. The risk of bias was high or unclear in 11 of the 13 included studies, and low in two studies. Both the education interventions delivered, and the outcome assessment tools used were heterogenous across included studies: meta-analysis was therefore not performed. Eight of 11 studies identified significantly better foot self care behaviour scores in individuals randomised to education compared with controls. Self efficacy scores were significantly better in education groups in four of five studies reporting this primary outcome. Foot care knowledge was significantly better in intervention vs. control in three of seven studies. In general, studies assessing secondary endpoints including quality of life and ulcer/amputation incidence tended not to identify significant clinical improvements. CONCLUSION: The available evidence is of inadequate quality to reliably conclude that foot care education has a positive impact on foot self care behaviour and self efficacy in individuals with diabetes. Quality data supporting accompanying benefits on quality of life or ulcer/amputation incidence are also lacking and should be considered as an important outcome measure in future studies.

Metabolic Phenotyping in Venous Disease: The Need for Standardization.

Venous thromboembolism (VTE), chronic venous disease (CVD), and venous leg ulceration (VLU) are clinical manifestations of a poorly functioning venous system. Though common, much is unknown of the pathophysiology and progression of these conditions. Metabolic phenotyping has been employed to explore mechanistic pathways involved in venous disease. A systematic literature review was performed: full text, primary research articles on the applications of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) in human participants and animals were included for qualitative synthesis. Seventeen studies applying metabolic phenotyping to venous disease were identified: six on CVD, two on VLU, and nine on VTE; both animal (n = 6) and human (n = 10) experimental designs were reported, with one study including both. NMR, MS, and MS imaging were employed to characterize serum, plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated in CVD included lipids, branched chain amino acids (BCAA), glutamate, taurine, lactate, and myo-inositol identified in vein tissue. Upregulated metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate, and glutamate identified in wound fluid and ulcer biopsies. VTE cases were associated with reduced carnitine levels, upregulated aromatic amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum, thrombus, and vein wall; kynurenine and tricarboxylic acid pathway dysfunction were reported. Future research should focus on targeted studies with internal and external validation.

The Relationship Between Vein Diameters, Clinical Severity, and Quality of Life: A Systematic Review.

OBJECTIVE/BACKGROUND: The aim was to summarise the evidence for the relationship between vein diameters and clinical severity, and elucidate the relationship between diameters and health related quality of life (HRQoL) METHODS: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The MEDLINE and Embase databases were searched from 1946 to 31 August 2018. Reference lists of included studies were searched for further relevant papers. Full text studies in English reporting the relationship between great and small saphenous vein diameters and clinical severity and/or HRQoL scores measured using validated instruments were included. All study designs were included. Studies that did not include relationships between these parameters, non-English studies, and studies focusing on non-truncal veins were excluded. Two reviewers independently performed the study selection, data extraction, and risk of bias assessment. RESULTS: Eleven eligible studies were identified, reporting on 2,732 limbs (range 22-681). Four studies correlated truncal vein diameter with both clinical severity and HRQoL, while seven reported only on clinical severity measures. Multiple instruments were used to quantify HRQoL and clinical severity. Seven studies assessed the relationship with CEAP class, with the majority observing a positive correlation between vein diameter and disease severity. Four studies found weak correlations with VCSS, with one showing correlations with VCSS components. No significant relationship between diameters and HRQoL scores was reported. One study also revealed no correlation with Aberdeen Varicose Vein Questionnaire improvements post-treatment. The majority of studies failed to include C0 and C1 participants. CONCLUSIONS: While further studies are required to improve the level of evidence, the existing literature suggests that truncal vein diameters correlate with clinical severity. Diameters are a poor predictor of HRQoL, with no relationship to patients' perceived impact of chronic venous disease. As such, vein diameter should not be used as a measure to decide who needs venous intervention.

Venous Leg Ulcer Clinical Practice Guidelines: What is AGREEd?

OBJECTIVE: The aim was to evaluate the quality of current venous leg ulcer (VLU) clinical practice guidelines (CPGs) to assist healthcare professionals in choosing an accessible high quality CPG to advise their practice, and to identify areas for improvement in future versions of current CPGs. METHODS: A systematic review of PubMed, Embase, online CPG databases, and reference lists of included CPGs was carried out. Full text CPGs published no earlier than 1998 reporting evidence based recommendations on VLU diagnosis and management in English were included. CPGs that were only available if purchased were excluded. Two reviewers identified eligible CPGs, extracted data, and assessed the quality independently using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Significant scoring discrepancies were discussed with a third reviewer. RESULTS: Fourteen eligible CPGs were identified (1999-2016). The majority of CPGs originated from Europe or North America. Overall, there was good inter-reviewer reliability of scores with an intraclass correlation coefficient of 0.986 (95% confidence interval 0.979-0.991). No single CPG achieved the highest score in all six domains. Significant methodological heterogeneity was observed across VLU CPGs; however, consistently, poor performance was noted in domain 5, concerning CPG applicability. CONCLUSION: Four CPGs were considered of adequate quality for clinical use. Consolidation of efforts to drive high quality, comprehensive VLU CPGs is necessary to reduce the number of and heterogeneity seen in currently published guidelines. Elements of methodological quality are lacking and a structured approach with use of checklists and CPG creation tools, such as AGREE II or others, may bolster rigour in future VLU CPGs.

Thrombophilia in non-thrombotic chronic venous disease of the lower limb - a systematic review.

Chronic venous disease (CVD) represents a significant healthcare burden. Thrombophilia is proposed as a risk factor, particularly for post-thrombotic CVD. A systematic review was performed to determine the relationship between thrombophilia and non-thrombotic CVD. MEDLINE® and Embase® databases were searched from 1946 up to March 2018. Case-control studies, cohort studies or randomised clinical trials reporting on thrombophilias in non-thrombotic lower limb CVD in adult patients were included. Non-English and post-thrombotic syndrome studies were excluded. Study selection and data extraction were performed by two reviewers. Fifteen studies were included, reporting on 916 cases and 1261 controls. Studies largely focused on venous ulceration and investigated multiple haemostatic factors. An association between thrombophilia and non-thrombotic CVD was identified, with greater prevalence and factor concentration alteration reported in patients compared to controls. Concomitant thrombophilia presence was associated with earlier CVD onset. Relationship strength varied, with commoner aetiologies showing clearer correlation than rarer ones. Thrombophilia is associated with non-thrombotic CVD but the mechanism is unclear and causation cannot be determined. Future research should focus on prospective studies with larger populations and identify adjunct therapies targeting thrombophilia.

A systematic review of anatomical reflux patterns in primary chronic venous disease.

OBJECTIVE: Patients with chronic venous disease (CVD) can present with different underlying hemodynamic abnormalities affecting the deep, superficial, and perforator veins. This review explores the relationship between reflux patterns, extent of venous reflux, and clinical manifestations of CVD. METHODS: The Medline and EMBASE databases were searched systematically from 1946 to April 1, 2024. References of shortlisted papers were searched for relevant articles. Studies were included if they were in English language, included participants ≥16 years of age, documented reflux patterns in two or more of the following: deep, superficial, and/or perforator systems, and related patterns to presentation or severity. Exclusion criteria included patients with isolated deep venous thrombosis, post-thrombotic syndrome or stenotic or obstructive disease. RESULTS: We identified 18 studies (11,177 participants; range, 55-3016). Meta-analysis showed significant odds ratios (OR) for C4-6 disease being associated with deep reflux (OR, 2.41; 95% confidence interval [CI], 1.53-3.78) and perforator reflux (OR, 3.37; 95% CI, 2.16-5.27), but not superficial reflux (OR, 2.11; 95% CI, 0.87-5.14), vs C0-3 disease. Severe CVD (C4-6) was significantly associated with isolated deep, combined deep and superficial, and combined superficial and perforator reflux. The greatest risk of CVD progression (defined as de novo development of varicose veins and progression to greater CVD severity) was shown by two studies to be related to combined deep and superficial reflux. CONCLUSIONS: Although limited by the heterogenous nature of the studies, this review confirms that reflux pattern is a significant predictor of clinical class, and higher clinical, etiological, anatomical, and pathophysiological stages are associated with a higher prevalence of superficial, deep, and perforator reflux. Isolated deep and combined reflux also seem to be to predict the onset of leg ulceration. Future studies should relate reflux patterns to treatment outcomes, including recurrence risk. This work could help to inform health policies and management guidelines so that reflux patterns, in conjunction with other demographic and hemodynamic parameters, could be used to risk stratify patients and identify individuals who may benefit from earlier treatment.

Postsclerotherapy compression: A systematic review.

BACKGROUND: Compression after sclerotherapy is commonly used, although the evidence base for this practice is unclear. This study aims to summarize and assess the evidence for compression therapy after sclerotherapy to inform clinical practice. METHODS: A systematic review was performed according to PRISMA guidelines via Medline and EMBASE databases (1946 to December 31, 2019) by two reviewers. Full-text, English-language studies comparing compression type and/or duration in adult chronic venous disease patients undergoing liquid or foam sclerotherapy were included. RESULTS: Nine studies were identified: five using liquid sclerotherapy, three foam sclerotherapy and one using both. Studies had short follow-up periods (6-24 weeks) and reported on clinical outcomes, quality of life, side effects and complications. In C1 patients undergoing liquid sclerotherapy, any duration of stocking use significantly decreased telangiectasia and reticular vein number and size compared with no compression. No significant difference in clinical symptoms or quality of life was seen when comparing compression duration after liquid or foam sclerotherapy in tributary or truncal veins in C2 to C6 patients. Greater superficial vein resolution was seen with stockings compared with bandages in C2 patients undergoing liquid sclerotherapy to tributary veins. A comparison of stockings vs bandaging revealed differing thrombophlebitis rates but no significant difference in pigmentation. In C2 to C6 patients undergoing foam sclerotherapy, use of 35 mm Hg stockings significantly improved post-treatment symptoms compared with 23 mm Hg stockings. This review was limited by heterogeneity of outcome measurements and the variety of comparisons between compression types and durations. CONCLUSIONS: Postsclerotherapy compression may have beneficial clinical outcomes at short-term follow-up; however, evidence is lacking regarding its type, class, length, and duration. Further trials are required to guide the optimal management of postsclerotherapy patients.

Ocular complications of oak processionary caterpillar setae in the Netherlands; case series, literature overview, national survey and treatment advice.

During early summer 2019, the Netherlands experienced an outbreak of the exotic oak processionary caterpillar. The vast number of caterpillars, which live in large nests on oak trees before they turn into moths, possess thousands of small, barbed hairs (setae) that are disseminated with the wind. The hairs cause a range of primarily dermatologic problems. However, Dutch ophthalmologists started reporting patients with ophthalmologic complaints caused by the penetrating hairs of the oak processionary caterpillar. This paper focuses on the ophthalmologic complications caused by the caterpillar hairs. We collected a series of four cases with reports ranging from a corneal erosion with hairs lodged into the cornea, to a sterile endophthalmitis in which hairs were found in the vitreous. A literature review for similar cases was performed using the PubMed and Embase database. Together with the Dutch Ophthalmic Society (Nederlands Oogheelkundig Gezelschap, NOG), a national survey was issued to determine the scale of this new problem. This showed that oak processionary caterpillar related complaints are primarily limited to the south of the Netherlands. Suggested ophthalmic treatment guidelines are presented. With the next summer at the doorstep, and limited preventative measures against the caterpillar hairs, we expect a new wave of ophthalmologic complaints coming year as well.

Phase-contrast magnetic resonance imaging and computational fluid dynamics assessment of thoracic aorta blood flow: a literature review.

The death rate from thoracic aortic disease is on the rise and represents a growing global health concern as patients are often asymptomatic before acute events, which have devastating effects on health-related quality of life. Biomechanical factors have been found to play a major role in the development of both acquired and congenital aortic diseases. However, much is still unknown and translational benefits of this knowledge are yet to be seen. Phase-contrast cardiovascular magnetic resonance imaging of thoracic aortic blood flow has emerged as an exceptionally powerful non-invasive tool enabling visualization of complex flow patterns, and calculation of variables such as wall shear stress. This has led to multiple new findings in the areas of phenotype-dependent bicuspid valve flow patterns, thoracic aortic aneurysm formation and aortic prosthesis performance assessment. Phase-contrast cardiovascular magnetic resonance imaging has also been used in conjunction with computational fluid modelling techniques to produce even more sophisticated analyses, by allowing the calculation of haemodynamic variables with exceptional temporal and spatial resolution. Translationally, these technologies may potentially play a major role in the emergence of precision medicine and patient-specific treatments in patients with aortic disease. This clinically focused review will provide a systematic overview of key insights from published studies to date.

Can activity monitors predict outcomes in patients with heart failure? A systematic review.

Actigraphy is increasingly incorporated into clinical practice to monitor intervention effectiveness and patient health in congestive heart failure (CHF). We explored the prognostic impact of actigraphy-quantified physical activity (AQPA) on CHF outcomes. PubMed and Medline databases were systematically searched for cross-sectional studies, cohort studies or randomised controlled trials from January 2007 to December 2017. We included studies that used validated actigraphs to predict outcomes in adult HF patients. Study selection and data extraction were performed by two independent reviewers. A total of 17 studies (15 cohort, 1 cross-sectional, 1 randomised controlled trial) were included, reporting on 2,759 CHF patients (22-89 years, 27.7% female). Overall, AQPA showed a strong inverse relationship with mortality and predictive utility when combined with established risk scores, and prognostic roles in morbidity, predicting cognitive function, New York Heart Association functional class and intercurrent events (e.g. hospitalisation), but weak relationships with health-related quality of life scores. Studies lacked consensus regarding device choice, time points and thresholds of PA measurement, which rendered quantitative comparisons between studies difficult. AQPA has a strong prognostic role in CHF. Multiple sampling time points would allow calculation of AQPA changes for incorporation into risk models. Consensus is needed regarding device choice and AQPA thresholds, while data management strategies are required to fully utilise generated data. Big data and machine learning strategies will potentially yield better predictive value of AQPA in CHF patients.

Quality of life after mitral valve intervention.

Advancements in surgical technique and understanding of the pathophysiology of mitral valve (MV) dysfunction have led to improved outcomes. Seen as a development beyond measures of morbidity and mortality, health-related quality-of-life (HRQOL) outcome measures are becoming increasingly popular. These measures are important because complications following routine (i.e. low-risk) operations on the MV are uncommon and further markers of outcome are needed. Surgeons are increasingly operating earlier on asymptomatic patients and will need to prove that HRQOL is not impacted. Novel minimally invasive and transcatheter technologies will also need to demonstrate satisfactory HRQOL outcomes prior to widespread use. This systematic review provides an overview of all available literature detailing HRQOL in patients receiving MV interventions. In the 43 studies included, 6865 patients underwent procedures ranging from open replacement to percutaneous repair using devices such as the Mitraclip Clip Delivery System (MitraClip) (Abbott Vascular, Santa Clara, CA, USA). Most studies performed baseline HRQOL assessment, allowing postinterventional comparison. While the underlying literature had deficiencies, most studies report acceptable postintervention HRQOL that was comparable to that of matched general populations. Patient-specific (e.g. female gender, renal dysfunction) and surgical-specific factors (e.g. replacement instead of repair, elevated transmitral gradient) were identified that predispose patients to poorer long-term HRQOL outcomes. These factors are important for clinicians developing strategies to maximize their HRQOL outcomes. Future randomized studies would benefit from HRQOL measurements at specific time points to allow large-scale comparisons. Establishing a common HRQOL instrument for use in MV intervention studies may support detailed comparisons between specific techniques. Physical activity monitors, physiological biomarkers and radiological markers could also be used as innovative indicators of functional outcome.