Hyperbaric oxygen therapy for chronic diabetic foot ulcers: An overview of systematic reviews.

OBJECTIVES: Hyperbaric oxygen therapy in the treatment of diabetic foot ulcer has been widely used in medical practice, but its clinical effect is not clear. The purpose of this overview of systematic reviews is to evaluate the clinical evidence of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers. METHODS: PubMed, Cochrane Library, Web of Knowledge, Embase, MEDLINE, Chinese National Knowledge Infrastructure Database, the Chongqing VIP Database, Chinese Biomedical Database, and Wanfang Database were searched in 1st December 2020. Systematic reviews (SRs) evaluating the effects of Hyperbaric oxygen therapy in people with diabetic foot ulcer were included. Methodological quality of the included SRs was assessed using the AMSTAR-2 tool. The quality of evidence of the primary studies was assessed using GRADE. The integrity of the included SRs was assessed using PRISMA. The bias risk of each SR was assessed using ROBIS evaluation tool. RESULTS: Eleven SRs/MAs met all inclusion criteria. According to the results of the AMSTAR-2, only 1 included review were rated critically as being of high quality, 6 included review were rated critically as being of medium quality. With PRISMA, the reporting checklist was relatively complete, but some reporting weaknesses remained in the topics of the protocol and registration, search strategy, and additional analyses. Based on the ROBIS tool, only five SRs/MAs had a low risk of bias. With the GRADE system, no high-quality evidence was found, and only 13 outcomes provided moderate-quality evidence. CONCLUSIONS: There is limited clinical evidence to support hyperbaric oxygen therapy in the treatment of diabetic foot ulcers, it is not recommended to routinely apply hyperbaric oxygen therapy to all patients with diabetic foot ulcers, especially those with non-ischemic diabetic foot ulcers. Hyperbaric oxygen therapy has certain potential to promote ulcer healing and reduce amputation rate in patients with ischemic diabetic foot ulcers, but due to the low quality and small quantity of the SRs/MAs supporting these results, high-quality studies with rigorous study designs and larger samples are needed before widespread recommendations can be made.

Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial.

Importance: Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin. Objective: To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities. Design, Setting, and Participants: This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020. Interventions: A combination of low-dose rivaroxaban and aspirin compared with aspirin alone. Main Outcomes and Measures: Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding. Results: The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%). Conclusions and Relevance: Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.

Treatment of Frostbite With Hyperbaric Oxygen Therapy: A Single Center's Experience of 22 Cases.

INTRODUCTION: Frostbite is well documented in the military and countries with extreme temperatures, and it is most likely due to increased exposure to cold temperatures and/or risk-taking behavior. Severity of injury depends on absolute temperature, wind chill, duration of exposure, wet or dry cold, immersion, clothing quality, and substance use. Hyperbaric oxygen therapy (HBOT) has been described as a treatment option but only in small case series. OBJECTIVE: The aim of this retrospective study is to describe the usage patterns, side effects, and outcomes of HBOT used as an adjunct to wound care at a single major Canadian university hospital. MATERIALS AND METHODS: A retrospective review of patients with frostbite injury admitted and treated with HBOT between January 2000 and March 2015 was performed. A total of 22 patients were studied. Available data included patient demographics, duration of exposure to cold temperature, severity of injury, time to HBOT, duration of therapy, side effects of therapy, concurrent therapies (dressing, anticoagulation, antibiotics), bone scan results, and consequent level of amputation. RESULTS: The cohort consisted mostly of men (18, 81.8%) and patient mean age of 40 years (range, 13-70 years). Ten patients (45.5%) were intoxicated at the time of injury, and psychiatric illness was implicated in 9 (40.9%) patients. Of the presented injuries, 17 (77.3%) had frostbite to the upper extremity. Bone scans were performed on 16 (72.7%) patients. In 4 patients, the absence of radiotracer activity correlated with a protective effect on subsequent amputation levels. All patients received anticoagulant therapy. Of the 22 patients, 16 (72.7%) experienced at least 1 side effect of HBOT, including otologic barotrauma, nausea, vomiting, anxiety, oxygen toxicity seizure, and myopic changes. All study patients recovered without permanent sequelae; it is unclear whether HBOT reduced soft-tissue damage or amputation rates. CONCLUSIONS: This is the largest cohort reported in the literature of patients with frostbite injuries treated with HBOT. Hyperbaric oxygen therapy may show positive impact on the demarcation level of frostbite and, despite the common side effects, it generally causes no long-term sequelae.

Infected bone resection plus adjuvant antibiotic-impregnated calcium sulfate versus infected bone resection alone in the treatment of diabetic forefoot osteomyelitis.

BACKGROUND: Managing with diabetic foot osteomyelitis (DFO) is challenging. Even after infective bone resection and thorough debridement, DFO is still difficult to cure and has a high recurrence rate. This retrospective study aims to compare the outcomes of two treatment methods, infected bone resection combined with adjuvant antibiotic-impregnated calcium sulfate and infected bone resection alone, for the treatment of diabetic foot osteomyelitis. METHODS: Between 2015 to 2017, 48 limbs (46 patients) with DFO met the criteria were included for assessment. 20 limbs (18 patients) were included in the calcium sulfate group (the CS group) in which vancomycin and/or gentamicin-impregnated calcium sulfate was used as an adjuvant after infected bone resection while 28 limbs (28 patients) as the control group were undergone infected bone resection only. Systemic antibiotics, postoperative wound care and offloading were continued to be applied following surgery in both groups. The time to healing, healing rate, recurrence rate and amputation rate were compared between the two groups. RESULTS: In total, 90% (18/20) limbs in the CS group as compared to 78.6% (22/28) infected limbs in the control group went to heal (P = 0.513). The Mean time to healing was 13.3 weeks in the CS group and 11.2 weeks in control group (P = 0.132). Osteomyelitis recurrence rate was 0% (0/18) in the CS group and 36.4% (8/22) in the control group (P = 0.014). Postoperative leakage in calcium sulfate group was 30.0% (6/20) with a mean duration of 8.5 weeks. Amputation rate in the control group was 7.1% (2/28) compared to 0% (0/20) in the CS group (P = 0.153). CONCLUSIONS: Antibiotic-impregnated calcium sulfate as an adjuvant prevents the recurrence of DFO but cannot improve the healing rate, reduce the postoperative amputation rate or shorten the time to healing. Prolonged postoperative leakage as the most common complication can be managed with regular dressing. LEVEL OF EVIDENCE: III, Retrospective Comparative Study.

Trends in the Types of Physicians Performing Partial Foot Amputations.

BACKGROUND: Partial foot amputations (PFAs) are often indicated for the treatment of severe infection, osteomyelitis, and critical limb ischemia, which consequently leads to irreversible necrosis. Many patients who undergo PFAs have concomitant comorbidities and generally present with a severe acute manifestation of the condition, such as gangrenous changes, systemic infection, or debilitating pain, which would then require emergency amputation on an inpatient basis. METHODS: The purpose of this study was to track the recent prevalence of PFAs and to investigate the current demographic trends of the physicians managing and performing PFAs, specifically regarding medical degree and specialty. Doctors of podiatric medicine are striving to achieve parity with their allopathic and osteopathic surgical counterparts and become a more prominent part of the multidisciplinary approach to limb salvage and emergency surgical treatment. This study evaluated 4 years (2009-2012) of PFA data from the Pennsylvania state inpatient database in the two most populated areas of Pennsylvania: Philadelphia and Allegheny counties. Statistics on medical schools were obtained directly from the accrediting bodies of allopathic, osteopathic, and podiatric medical schools. The goal of this study was to evaluate the general trends of patients undergoing a PFA and to quantify the upswing of podiatric surgeons intervening in the surgical care of these patients. RESULTS: The number of partial foot amputations in the United States rose from 2006 to 2012. Podiatric surgeons performed 46% of theses procedures for residents of Philadelphia County from 2009 to 2012. In Allegheny County podiatric physicians performed 42% of these procedures during the same time frame. CONCLUSIONS: Partial foot amputations are increasing over time. Podiatric Surgeons perform a significant share of these operations. This share is increasing in the most populated areas of Pennsylvania.

Systematic review and meta-analysis of clinical trials examining the effect of hyperbaric oxygen therapy in people with diabetes-related lower limb ulcers.

AIM: To examine the efficacy of hyperbaric oxygen therapy in healing diabetes-related lower limb ulcers through a meta-analysis of randomized clinical trials. METHODS: A literature search was conducted to identify appropriate clinical trials. Inclusion required randomized study design and reporting of the proportion of diabetes-related lower limb ulcers that healed. A meta-analysis was performed to examine the effect of hyperbaric oxygen therapy on ulcer healing. The secondary outcomes were minor and major amputations. RESULTS: Nine randomized trials involving 585 participants were included. People allocated to hyperbaric oxygen therapy were more likely to have complete ulcer healing (relative risk 1.95, 95% CI 1.51-2.52; P<0.001), and less likely to require major (relative risk 0.54, 95% CI 0.36-0.81; P=0.003) or minor (relative risk 0.68, 95% CI 0.48-0.98; P=0.040) amputations than control groups. Sensitivity analyses suggested the findings were dependent on the inclusion of one trial. Adverse events included ear barotrauma and a seizure. Many of the trials were noted to have methodological weaknesses including absence of blinding of outcome assessors, lack of a justifiable sample size calculation and limited follow-up. CONCLUSIONS: This meta-analysis suggests hyperbaric oxygen therapy improves the healing of diabetes-related lower limb ulcers and reduces the requirement for amputation. Confidence in these results is limited by significant design weaknesses of previous trials and inconsistent findings. A more rigorous assessment of the efficacy of hyperbaric the efficacy of hyperbaric oxygen therapy is needed.

The clinical use of hyperbaric oxygen in the treatment of Danish patients with diabetic foot ulcers.

INTRODUCTION: Patients with diabetic foot ulcers (DFU) suffer from diabetes-related complications and comor-bidities. Hyperbaric oxygen therapy (HBOT) is a treatment modality with limited capacity used in the treatment of DFUs. It is important to ensure that HBOT is offered to patients who are suitable for this treatment regarding effect, compliance and life expectancy. The objective of the present study was to describe the population of patients with DFU who were referred to HBOT in Denmark in the 1999-2016 period. METHODS: All patients with DFU who were treated at the HBOT chamber in Copenhagen during the study period were considered. Patients with an invalid social security number or an incorrect diagnosis were excluded. Data on comor-bidities, amputation and death were extracted from the Danish National patient Registry and the Danish Civil Registration System. Continuous data were described as median values and binary data were described as proportions. The probability estimate for survival and amputation was investigated by constructing Kaplan-Meier curves. RESULTS: The cohort included 148 patients. Patients were mainly referred from the Capital Region (92%) and multi-disciplinary wound care centres were the primary referring departments (67%). Comorbidity rates were high with an initial median Charlson Comorbidity Index score of five. The five-year amputation and mortality estimates after referral were 73.5% and 51.8%, respectively. CONCLUSIONS: The study showed that Danish DFU patients who are offered HBOT are in advanced stages of their disease, and the referral hinges on local factors such as geography and the referring source rather than on standardised procedures. FUNDING: none. TRIAL REGISTRATION: not relevant.

Use of in-chamber transcutaneous oxygen measurement to determine optimal treatment pressure in patients undergoing hyperbaric oxygen therapy.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is used to promote healing in select problem wounds. Transcutaneous oxygen measurement (TCOM) can be used to predict the response of these wounds to HBO2, with in-chamber TCOM values shown to be the most predictive. We evaluated the use of in-chamber TCOM values to determine optimal treatment pressure. METHODS: A retrospective review was completed of patients undergoing HBO2 therapy for a lower-extremity wound and who had in-chamber TCOM. Data collected included TCOM values, treatment profile, and patient outcome. RESULTS: A total of 142 patients were identified. The overall results demonstrated healing in 59%, minor amputation (below ankle) in 11.3%, and major amputation (above ankle) in 16.2% of patients. 79.3% of patients at 2 atmospheres absolute (ATA) and 86.6% of patients at 2.4 ATA had transcutaneous oxygen pressure (TcPO2) values ≥250 mmHg. Among those with TcPO2 ⟨250 mmHg at 2 ATA, 41% attained TcPO2 ⟩250 mmHg at 2.4 ATA. Among those treated at 2 ATA the healing rate was 70.6% if TcPO2 ⟩250 mmHg, and 11.8% if TcPO2 ⟨250 mmHg (P⟨0.001). Among those treated at 2.4 ATA the healing rate was 33.3% if TcPO2 ⟩250 mmHg and 14.3% if TcPO2 ⟨250 mmHg (P⟨0.001). DISCUSSION: Determining optimal therapeutic pressure for patients undergoing HBO2 is important to maximize benefit and minimize risk. This study indicates that in-chamber TCOM can be used to select an individualized optimal treatment pressure in patients undergoing HBO2 for lower-extremity wounds, including diabetic foot ulcers. This may result in better utilization of HBO2 and better outcomes.

Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients.

BACKGROUND: Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of patients who are not suitable for or have failed previous revascularisation therapy (the 'no-option' CLI patients), limb amputation is eventually unavoidable. Preliminary studies have reported encouraging outcomes with autologous cell-based therapy for the treatment of CLI in these 'no-option' patients. However, studies comparing the angiogenic potency and clinical effects of autologous cells derived from different sources have yielded limited data. Data regarding cell doses and routes of administration are also limited. OBJECTIVES: To compare the efficacy and safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients. SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and trials registries (16 May 2018). Review authors searched PubMed until February 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving 'no-option' CLI patients comparing a particular source or regimen of autologous cell-based therapy against another source or regimen of autologous cell-based therapy. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility and methodological quality of the trials. We extracted outcome data from each trial and pooled them for meta-analysis. We calculated effect estimates using a risk ratio (RR) with 95% confidence interval (CI), or a mean difference (MD) with 95% CI. MAIN RESULTS: We included seven RCTs with a total of 359 participants. These studies compared bone marrow-mononuclear cells (BM-MNCs) versus mobilised peripheral blood stem cells (mPBSCs), BM-MNCs versus bone marrow-mesenchymal stem cells (BM-MSCs), high cell dose versus low cell dose, and intramuscular (IM) versus intra-arterial (IA) routes of cell implantation. We identified no other comparisons in these studies. We considered most studies to be at low risk of bias in random sequence generation, incomplete outcome data, and selective outcome reporting; at high risk of bias in blinding of patients and personnel; and at unclear risk of bias in allocation concealment and blinding of outcome assessors. The quality of evidence was most often low to very low, with risk of bias, imprecision, and indirectness of outcomes the major downgrading factors.Three RCTs (100 participants) reported a total of nine deaths during the study follow-up period. These studies did not report deaths according to treatment group.Results show no clear difference in amputation rates between IM and IA routes (RR 0.80, 95% CI 0.54 to 1.18; three RCTs, 95 participants; low-quality evidence). Single-study data show no clear difference in amputation rates between BM-MNC- and mPBSC-treated groups (RR 1.54, 95% CI 0.45 to 5.24; 150 participants; low-quality evidence) and between high and low cell dose (RR 3.21, 95% CI 0.87 to 11.90; 16 participants; very low-quality evidence). The study comparing BM-MNCs versus BM-MSCs reported no amputations.Single-study data with low-quality evidence show similar numbers of participants with healing ulcers between BM-MNCs and mPBSCs (RR 0.89, 95% CI 0.44 to 1.83; 49 participants) and between IM and IA routes (RR 1.13, 95% CI 0.73 to 1.76; 41 participants). In contrast, more participants appeared to have healing ulcers in the BM-MSC group than in the BM-MNC group (RR 2.00, 95% CI 1.02 to 3.92; one RCT, 22 participants; moderate-quality evidence). Researchers comparing high versus low cell doses did not report ulcer healing.Single-study data show similar numbers of participants with reduction in rest pain between BM-MNCs and mPBSCs (RR 0.99, 95% CI 0.93 to 1.06; 104 participants; moderate-quality evidence) and between IM and IA routes (RR 1.22, 95% CI 0.91 to 1.64; 32 participants; low-quality evidence). One study reported no clear difference in rest pain scores between BM-MNC and BM-MSC (MD 0.00, 95% CI -0.61 to 0.61; 37 participants; moderate-quality evidence). Trials comparing high versus low cell doses did not report rest pain.Single-study data show no clear difference in the number of participants with increased ankle-brachial index (ABI; increase of > 0.1 from pretreatment), between BM-MNCs and mPBSCs (RR 1.00, 95% CI 0.71 to 1.40; 104 participants; moderate-quality evidence), and between IM and IA routes (RR 0.93, 95% CI 0.43 to 2.00; 35 participants; very low-quality evidence). In contrast, ABI scores appeared higher in BM-MSC versus BM-MNC groups (MD 0.05, 95% CI 0.01 to 0.09; one RCT, 37 participants; low-quality evidence). ABI was not reported in the high versus low cell dose comparison.Similar numbers of participants had improved transcutaneous oxygen tension (TcO2) with IM versus IA routes (RR 1.22, 95% CI 0.86 to 1.72; two RCTs, 62 participants; very low-quality evidence). Single-study data with low-quality evidence show a higher TcO2 reading in BM-MSC versus BM-MNC groups (MD 8.00, 95% CI 3.46 to 12.54; 37 participants) and in mPBSC- versus BM-MNC-treated groups (MD 1.70, 95% CI 0.41 to 2.99; 150 participants). TcO2 was not reported in the high versus low cell dose comparison.Study authors reported no significant short-term adverse effects attributed to autologous cell implantation. AUTHORS' CONCLUSIONS: Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.

Reducing Amputations in People with Diabetes (RAPID): Evaluation of a New Care Pathway.

People with diabetes are at increased risk of foot ulcers, which, if left untreated, can lead to infection, gangrene, and subsequent amputation. Management by a multidisciplinary diabetes foot team has been shown to reduce amputation rates; however, accessing specialist treatment is made particularly difficult when living in remote and rural locations, such as many individuals cared for within NHS Highland. The RAPID project was made up of two phases: firstly, to evaluate the technical feasibility of a new integrated care pathway using innovative technology, and secondly, to establish process enhancement of the pathway to justify a larger-scale study. Omni-HubTM enabled a face-to-face consultation by the community podiatrist to be enhanced by virtual consultation with members of the multidisciplinary foot team, including specialist diabetes podiatrists and a diabetes consultant. The technical feasibility study provided recommended changes focused around adaptations to the equipment used and the best means to gain successful connectivity. The process enhancement study demonstrated positive outcomes in the process with positive effects both in the service received by patients and experiences of healthcare professionals involved. The RAPID project provides evidence and justification for a larger-scale empirical study to test an embedded pathway and technology solution, which will inform policy change and a paradigm shift in the management of foot ulceration in the community.

Burden of disease from lower limb amputations attributable to diabetes mellitus in Santa Catarina State, Brazil, 2008-2013. / Carga da doença para as amputações de membros inferiores atribuíveis ao diabetes mellitus no Estado de Santa Catarina, Brasil, 2008-2013.

The objective was to estimate the burden of disease from lower limb amputations attributable to diabetes mellitus in Santa Catarina State, Brazil, from 2008 to 2013. A descriptive epidemiological study was performed by calculating disability-adjusted life years (DALY). Burden of disease was high, more than 8,000 DALY in men and women. Disability accounted for 93% of DALY and mortality for 7.5%. The burden in men was 5,580.6 DALY, almost double that in women (2,894.8), and the share of the years lost due to disability (YLD) component in men pushed this rate to 67.6% of total DALY. Men live longer following amputation, so they lose more years of healthy life (65.8%), while mortality is higher in women (61%). DALY rates were not distributed homogeneously across the state. The intensification of evaluation, planning, and development of cost-effective strategies for prevention and health education for diabetic foot should be oriented according to higher male vulnerability.

O objetivo foi estimar a carga da doença para as amputações de membros inferiores atribuíveis ao diabetes mellitus no Estado de Santa Catarina, Brasil, no período de 2008 a 2013. Realizou-se um estudo epidemiológico descritivo, utilizando-se o cálculo de anos de vida perdidos ajustados por incapacidade (DALY - disability-adjusted life years). A carga da doença foi alta, mais de 8 mil DALY, distribuídos entre homens e mulheres. A incapacidade respondeu por 93% do DALY e a mortalidade por 7,5%. A carga dos homens foi 5.580,6 DALY, praticamente o dobro das mulheres (2.894,8), sendo que a participação do componente anos de vida saudável perdidos em virtude de incapacidade (YLD - years lost due to disability) dos homens impulsionou esta taxa para 67,6% do total do DALY. Os homens vivem mais tempo com a amputação, por isto perdem mais anos de vida sadia (65,8%), e a mortalidade é maior entre as mulheres (61%). As distribuições das taxas de DALY no estado não mostraram distribuição homogênea. A intensificação de avaliação, planejamento e desenvolvimento de estratégias custo-efetivas para a prevenção e educação em saúde para o pé diabético deve ser considera a partir da maior vulnerabilidade masculina.

El objetivo fue estimar la carga de enfermedad para las amputaciones de miembros inferiores, atribuibles a la diabetes mellitus en el Estado de Santa Catarina, Brasil, durante el período de 2008 a 2013. Se realizó un estudio epidemiológico descriptivo, utilizándose el cálculo de años de vida ajustados por discapacidad (DALY - disability-adjusted life years). La carga de la enfermedad fue alta, más de 8 mil DALY distribuidos entre hombres y mujeres. La incapacidad supuso un 93% del DALY y la mortalidad un 7,5%. La carga de los hombres fue 5.580,6 DALY, prácticamente el doble de las mujeres (2.894,8), siendo que la participación del componente años de vida saludable perdidos por discapacidad (YLD - years lost due to disability) de los hombres impulsó esta tasa hacia un 67,6% del total del DALY. Los hombres viven más tiempo con la amputación, por ello pierden más años de vida sana (65,8%), y la mortalidad es mayor entre las mujeres (61%). Las distribuciones de las tasas de DALY en el estado no mostraron distribución homogénea. La intensificación de evaluación, planificación y desarrollo de estrategias costo-efectivas para la prevención y educación en salud para el pie diabético debe ser considerada a partir de la mayor vulnerabilidad masculina.

Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING: Bayer AG.

Carga da doença para as amputações de membros inferiores atribuíveis ao diabetes mellitus no Estado de Santa Catarina, Brasil, 2008-2013 / Carga de enfermedad para las amputaciones de miembros inferiores, atribuibles a la diabetes mellitus en el Estado de Santa Catarina, Brasil, 2008-2013 / Burden of disease from lower limb amputations attributable to diabetes mellitus in Santa Catarina State, Brazil, 2008-2013

O objetivo foi estimar a carga da doença para as amputações de membros inferiores atribuíveis ao diabetes mellitus no Estado de Santa Catarina, Brasil, no período de 2008 a 2013. Realizou-se um estudo epidemiológico descritivo, utilizando-se o cálculo de anos de vida perdidos ajustados por incapacidade (DALY - disability-adjusted life years). A carga da doença foi alta, mais de 8 mil DALY, distribuídos entre homens e mulheres. A incapacidade respondeu por 93% do DALY e a mortalidade por 7,5%. A carga dos homens foi 5.580,6 DALY, praticamente o dobro das mulheres (2.894,8), sendo que a participação do componente anos de vida saudável perdidos em virtude de incapacidade (YLD - years lost due to disability) dos homens impulsionou esta taxa para 67,6% do total do DALY. Os homens vivem mais tempo com a amputação, por isto perdem mais anos de vida sadia (65,8%), e a mortalidade é maior entre as mulheres (61%). As distribuições das taxas de DALY no estado não mostraram distribuição homogênea. A intensificação de avaliação, planejamento e desenvolvimento de estratégias custo-efetivas para a prevenção e educação em saúde para o pé diabético deve ser considera a partir da maior vulnerabilidade masculina.

El objetivo fue estimar la carga de enfermedad para las amputaciones de miembros inferiores, atribuibles a la diabetes mellitus en el Estado de Santa Catarina, Brasil, durante el período de 2008 a 2013. Se realizó un estudio epidemiológico descriptivo, utilizándose el cálculo de años de vida ajustados por discapacidad (DALY - disability-adjusted life years). La carga de la enfermedad fue alta, más de 8 mil DALY distribuidos entre hombres y mujeres. La incapacidad supuso un 93% del DALY y la mortalidad un 7,5%. La carga de los hombres fue 5.580,6 DALY, prácticamente el doble de las mujeres (2.894,8), siendo que la participación del componente años de vida saludable perdidos por discapacidad (YLD - years lost due to disability) de los hombres impulsó esta tasa hacia un 67,6% del total del DALY. Los hombres viven más tiempo con la amputación, por ello pierden más años de vida sana (65,8%), y la mortalidad es mayor entre las mujeres (61%). Las distribuciones de las tasas de DALY en el estado no mostraron distribución homogénea. La intensificación de evaluación, planificación y desarrollo de estrategias costo-efectivas para la prevención y educación en salud para el pie diabético debe ser considerada a partir de la mayor vulnerabilidad masculina

The objective was to estimate the burden of disease from lower limb amputations attributable to diabetes mellitus in Santa Catarina State, Brazil, from 2008 to 2013. A descriptive epidemiological study was performed by calculating disability-adjusted life years (DALY). Burden of disease was high, more than 8,000 DALY in men and women. Disability accounted for 93% of DALY and mortality for 7.5%. The burden in men was 5,580.6 DALY, almost double that in women (2,894.8), and the share of the years lost due to disability (YLD) component in men pushed this rate to 67.6% of total DALY. Men live longer following amputation, so they lose more years of healthy life (65.8%), while mortality is higher in women (61%). DALY rates were not distributed homogeneously across the state. The intensification of evaluation, planning, and development of cost-effective strategies for prevention and health education for diabetic foot should be oriented according to higher male vulnerability.

Amputation predictors in diabetic foot ulcers treated with hyperbaric oxygen.

OBJECTIVE: Although hyperbaric oxygen therapy (HBOT) has long been used for diabetic foot ulcers (DFUs), its effectiveness is still controversial. The aim of this study was to investigate the efficacy of HBOT in the management of DFUs and identify amputation predictors. METHOD: Patients with chronic DFUs (Wanger grade 2-5) were included in the study, which took place between January 2010 and December 2012. HBOT, 100% oxygen, 2.4 atmosphere absolute (ATA) for 120 minutes, was administered to all patients in addition to standard treatment. DFUs were monitored for at least 3 years, or until healing or amputation occurred. RESULTS: Patients with a total of 146 chronic DFUswere recruited. Complete healing (69.6%) and significant improvement (17.9%) was observed in 87.5% of the patients. The cases with no improvement resulted in amputation (minor amputation: 15.0%; major amputation: 8.2%). The duration of diabetes (p=0.037), new wound formation (p=0.045), C-reactive protein (p=0.001) and Wagner grade (p=0.0001) were correlated with amputation in multiple regression analysis. Mortality was higher in the amputation group than in the non-amputation group (47.1 % versus 21.4 %, p=0.007). CONCLUSION: The inclusion of HBOT with standard treatment and a multidisciplinary approach may be useful in the treatment of DFUs. We found the most important predictors of amputation to be Wagner grade and wound infection. Multicentre, prospective, randomised studies are needed to provide more evidence.

The Incidence of Confounding Factors in Patients With Diabetes Mellitus Hospitalized for Diabetic Foot Ulcers.

INTRODUCTION: Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healing challenges of diabetic foot ulcers (DFUs). This paper reports the occurrences of these factors that the authors label the "Troublesome Triad" (TT) in a prospective series of 62 patients with diabetes mellitus (DM), who were hospitalized because of their DFUs. MATERIALS AND METHODS: With Institutional Review Board approval, the authors gathered data in a prospective series of patients hospitalized because of lower extremity wounds. From this data, they analyzed the DFU cohort for the incidence of each of the components of the TT. The severity of the wound was graded with the authors' 0 to 10 Wound Score in the patients who had components of the TT and compared with those who did not. RESULTS: One or more components of the TT were observed in 57 patients (91.9%). As the number of confounders increased, mean Wound Scores decreased from 5.2 for 1 confounder to 2.9 for 3 confounders (P = 0.003). Most patients had 1 or 2 confounders (38.7% and 45.2%, respectively), while only 5 (8.1%) patients had all 3 confounders. Unresolved infection was the major confounder in 38 (61.3%) patients, uncontrolled deformity in 31 (50.0%), and ischemia-hypoxia in 26 (41.9%). CONCLUSION: For those patients with DM who were hospitalized because of DFUs, confounders that require remedial interventions were present in more than 90% of patients. Recognition and management of the TT eliminates wasteful uses of resources in an attempt to heal lower extremity wounds in patients with DM where the confounders need to be addressed first.

The Geriatric Nutritional Risk Index is Independently Associated with Prognosis in Patients with Critical Limb Ischemia Following Endovascular Therapy.

OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 ± 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI ≥ 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI.

Cost and mortality data of a regional limb salvage and hyperbaric medicine program for Wagner Grade 3 or 4 diabetic foot ulcers.

We obtained costs and mortality data in two retrospective cohorts totaling 159 patients who have diabetes mellitus and onset of a diabetic foot ulcer (DFU). Data were collected from 2005 to 2013, with a follow-up period through September 30, 2014. A total of 106 patients entered an evidence-based limb salvage protocol (LSP) for Wagner Grade 3 or 4 (WG3/4) DFU and intention-to-treat adjunctive hyperbaric oxygen (HBO2) therapy. A second cohort of 53 patients had a primary lower extremity amputation (LEA), either below the knee (BKA) or above the knee (AKA) and were not part of the LSP. Ninety-six of 106 patients completed the LSP/HBO2with an average cost of USD $33,100. Eighty-eight of 96 patients (91.7%) who completed the LSP/HBO2had intact lower extremities at one year. Thirty-four of the 96 patients (35.4%) died during the follow-up period. Costs for a historical cohort of 53 patients having a primary major LEA range from USD $66,300 to USD $73,000. Twenty-five of the 53 patients (47.2%) died. The difference in cost of care and mortality between an LSP with adjunctive HBO2therapy vs. primary LEA is staggering. We conclude that an aggressive limb salvage program that includes HBO2 therapy is cost-effective.