scholarly journals Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN Study.

2020 ◽  
Author(s):  
Olufunmilayo O Adeleye ◽  
Ejiofor T Ugwu ◽  
Ibrahim D Gezawa ◽  
Innocent Okpe ◽  
Ignatius Ezeani ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Hospital Mortality ◽  
Cardiac Failure ◽  
Diabetic Foot ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Diabetic Foot Ulcers ◽  
Grade 3

Abstract Background: Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. This study was undertaken to determine factors that predict mortality in patients hospitalized for DFU in Nigeria.Methods:The current study was part of Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN), an observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented to participate were recruited and subjected to relevant clinical, biochemical and radiological assessments and multidisciplinary care until discharge or death. Data for type 1 diabetes mellitus (DM) patients were expunged from current mortality analysis due to their small number.Results: Three hundred and twenty three type 2 DM subjects with mean age and mean duration of DM of 57.2 11.4 years and 8.7± 5.8 years respectively participated in this study. The median duration of ulcers was 39 days with a range of 28 to 54 days and majority (79.9%) presented with advanced ulcers of at least Wagner grade 3. Mortality of 21.4% was recorded in the study, with the highest mortality observed among subjects with Wagner grade 5. Variables significantly associated with mortality with their respective p values were DM duration more than 120 months (p 0.005), ulcer duration > one month (p 0.020), ulcer severity of Wagner grade 3 and above (p 0.001), peripheral arterial disease (p 0.005), proteinuria (p <0.001), positive blood cultures (p<0.001), low HDL (p <0.001), shock at presentation (p<0.001), cardiac failure (p 0.027),and renal impairment (p <0.001). On Multivariate regression analysis, presence of bacteraemia (OR 5.053; 95% CI 2.572-9.428) and renal impairment (OR 2.838; 95% CI 1.349 – 5.971) were significantly predictive of mortality independent of other variables.Conclusions: This study showed high intra-hospital mortality among patients with DFU, with majority of deaths occurring among those with advanced ulcers, bacteremia, cardiac failure and renal impairment. Prompt attention to these factors might be helpful in improving survival from DFU in Nigeria.

scholarly journals Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN Study.

2020 ◽  
Author(s):  
Olufunmilayo O Adeleye ◽  
Ejiofor T Ugwu ◽  
Ibrahim D Gezawa ◽  
Innocent Okpe ◽  
Ignatius Ezeani ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Diabetic Foot ◽  
Arterial Disease ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Low Hdl ◽  
Vascular Stenosis ◽  
Grade 3 ◽  
Peripheral Arterial

Abstract Background/Objective: Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. This study is to document contributory factors that predict mortality in patients hospitalized for DFU in Nigeria. Methods: Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN), an observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented. Co-morbid complications were documented. Results: Mean age 55.9 +/- 12.5 years. 96.1% had type 2 diabetes (DM), the mean duration of DM was 8.5 ± 5.7 years. The duration of ulcers was 39 days with a range of 28 to 54 days. 79.2% presented with at least grade 3 DFU. About one-fifth of the patients died (20.5%). Highest mortality among subjects with Wagner grade 5. Middle-aged subjects (45-64 years) had significantly high mortality- odds ratio (OR) 5.107, Confidence interval (CI) of 1.429-18.252.Variables significantly associated with mortality with the respective p- values are DM duration more than 120 months (0.008), ulcer duration > one month (0.013), ulcer severity of Wagner grade 3 and above (0.001), peripheral arterial disease (0.002), foot gangrene (< 0.001). Laboratory variables associated with mortality; proteinuria (<0.001), positive blood cultures (<0.001), severe vascular stenosis (0.001), moderate vascular stenosis (< 0.001), Low HDL (< 0.001). Co-morbid complications significantly associated with mortality; shock at presentation (<0.001), anaemia (0.034), cardiac failure (0.020), renal impairment (<0.001). Sepsis was the strongest predictor of mortality (OR 5.128; 95% CI 2.614 – 10.060) followed by renal impairment (OR 2.831; 95% CI 1.346 – 5.953). Conclusions: Mortality among Nigerian diabetic patients admitted for DFU is high. The majority who died during hospitalization for DFU belong to the working-age population. Predictors of mortality were older age, higher Wagner grade (≥ 3) ulcer, longer duration of DM, longer duration of ulcer, peripheral arterial disease, foot gangrene, renal impairment, low HDL- cholesterol, anaemia, shock, and cardiac failure. Renal impairment and positive blood culture were independent determinants of mortality.

scholarly journals Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN Study.

2019 ◽  
Author(s):  
OLUFUNMILAYO OLUBUSOLA ADELEYE ◽  
Ejiofor T Ugwu ◽  
Ibrahim D Gezawa ◽  
Innocent Okpe ◽  
Ignatius Ezeani ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Diabetic Foot ◽  
Arterial Disease ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Low Hdl ◽  
Vascular Stenosis ◽  
Grade 3 ◽  
Peripheral Arterial

Abstract Background/Objective : Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. We sought to document contributory factors which predict mortality in patients hospitalized for DFU. Methods : Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria ( MEDFUN ), one-year observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented. Co-morbid complications were documented. Results : Mean age 55.9 12.5 years.96.1% had type 2 diabetes (DM), mean duration of DM was 8.5 ± 5.7 years. Duration of ulcer was 39 days with a range of 28 to 54 days. 79.2% presented with at least grade 3 DFU. About one-fifth of the patients died (20.5%). Highest mortality among subjects with Wagner grade 5. Middle-aged subjects ( 45-64 years) had significantly higher mortality- odds ratio (OR) 5.107, Confidence interval (CI) of 1.429-18.252, and P-value 0.022. Variables significantly associated with mortality with the respective p- values are DM duration more than 120 months (0.008), ulcer duration > one month (0.013), ulcer severity of Wagner grade 3 and above (0.001), peripheral arterial disease (0.002), foot gangrene (< 0.001). Laboratory variables associated with mortality ; proteinuria (<0.001), positive blood cultures (<0.001), severe vascular stenosis (0.001), moderate vascular stenosis(< 0.001), Low HDL (< 0.001). Co-morbid complications significantly associated with mortality; shock at presentation (<0.001), anemia (0.034), cardiac failure (0.020), renal impairment (<0.001). Sepsis was the strongest predictor of mortality (adjusted OR 5.128; 95% CI 2.614 – 10.060) followed by renal impairment (adjusted OR 2.831; 95% C.I. for OR 1.346 – 5.953). Conclusions : Mortality among Nigerian diabetic patients admitted for DFU is high, univariate predictors of mortality: older age, higher Wagner grade (≥ 3) ulcer, longer duration of DM, longer duration of ulcer, peripheral arterial disease, foot gangrene, renal impairment, low HDL- cholesterol, anemia, shock, and cardiac failure. Renal impairment and positive blood culture were independent determinants of mortality.

scholarly journals Plectranthus amboinicusandCentella asiaticaCream for the Treatment of Diabetic Foot Ulcers

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yuan-Sung Kuo ◽  
Hsiung-Fei Chien ◽  
William Lu
Keyword(s):  
Diabetic Foot ◽  
Statistical Significance ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Open Label ◽  
Safe Alternative ◽  
Significant Difference ◽  
Grade 3

Effects of a topical cream containingP. amboinicus(Lour.) Spreng. (Lamiaceae) andC. asiatica(L.) Urban (Umbelliferae) were evaluated and compared to effects of hydrocolloid fiber wound dressing for diabetic foot ulcers. A single-center, randomized, controlled, open-label study was conducted. Twenty-four type 1 or type 2 diabetes patients aged 20 years or older with Wagner grade 3 foot ulcers postsurgical debridement were enrolled between October 2008 and December 2009. Twelve randomly assigned patients were treated with WH-1 cream containingP. amboinicusandC. asiaticatwice daily for two weeks. Another 12 patients were treated with hydrocolloid fiber dressings changed at 7 days or when clinically indicated. Wound condition and safety were assessed at days 7 and 14 and results were compared between groups. No statistically significant differences were seen in percent changes in wound size at 7- and 14-day assessments of WH-1 cream and hydrocolloid dressing groups. A slightly higher proportion of patients in the WH-1 cream group (10 of 12; 90.9%) showed Wagner grade improvement compared to the hydrocolloid fiber dressing group but without statistical significance. For treating diabetic foot ulcers,P. amboinicusandC. asiaticacream is a safe alternative to hydrocolloid fiber dressing without significant difference in effectiveness.

scholarly journals The Role of VEGF and TNF-Alpha on Epithelialization of Diabetic Foot Ulcers after Hyperbaric Oxygen Therapy

2019 ◽  
Vol 7 (19) ◽  
pp. 3177-3183 ◽  
Author(s):  
I Nyoman Semadi
Keyword(s):  
Hyperbaric Oxygen ◽  
Diabetic Foot ◽  
Hyperbaric Oxygen Therapy ◽  
Oxygen Therapy ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Diabetic Foot Ulcers ◽  
Tnf Α

BACKGROUND: Around 15-25% of diabetes mellitus (DM) patients will develop diabetic foot ulcers (DFUs) with high morbidity, many studies have been proposed to search the most effective healing techniques. AIM: This study was conducted to demonstrate the ability of hyperbaric oxygen therapy (HBOT) as a complementary therapy in DFUs healing through raising vascular endothelial growth factor (VEGF) levels and suppressing tumour necrosis factor-alpha (TNF-α). METHODS: All patients received the same treatment including wound debridement and wound care, but the patients in the HBOT group, breathed 100% oxygen at 2.4 ATA for 90 minutes in total of 20 sessions (four weeks). RESULT: There were 32 diabetic patients with DFUs Wagner 3-4. VEGF levels after four weeks of HBOT was significantly elevated compared to the control group (p = 0.013). The effect size of VEGF levels was p = 0.005. TNF-α levels after four weeks of therapy were decreased (p = 0.01). Faster epithelialization is seen in the HBOT group (p < 0.001). We also performed path analysis, HBOT had a significant effect on the epithelialization (p < 0.001) and VEGF levels affected the epithelialization process (p = 0.042). CONCLUSION: HBOT administration leads to increased VEGF levels, decreased TNF-α levels, and accelerated wound healing of DFUs patients. HBOT directly aids epithelialization and indirectly through VEGF upsurge and TNF-α downturn.

scholarly journals Staphylococcus aureus strains isolated from diabetic foot ulcers. Identification of the antibiotic resistant phenotypes

2013 ◽  
Vol 20 (4) ◽  
pp. 389-393 ◽  
Author(s):  
Teodora Chiţă ◽  
Delia Muntean ◽  
Luminiţa Badiţoiu ◽  
Bogdan Timar ◽  
Roxana Moldovan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Staphylococcus Aureus ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Foot Ulcers ◽  
Resistance Pattern ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Bacterial Strains ◽  
Diabetes Clinic

Abstract Background and aims: Infected foot ulcer is one of the most feared complications of diabetes mellitus. Staphylococcus aureus is the most frequently isolated pathogen in diabetic foot infections. The aim of this study was to evaluate the prevalence of S. aureus strains involved in producing foot infections in diabetic patients and the antibiotic resistance pattern of these strains. Material and methods: The study included 33 S. aureus strains isolated from 55 diabetic foot ulcers. The subjects were selected from the 2465 patients with diabetes mellitus hospitalized in the Timişoara Diabetes Clinic, between 2011 and 2013. Germs’ identification relied on cultural and biochemical characteristics. Final identification and antimicrobial testing were performed using the Vitek 2 (Bio Merieux France) automatic analyzer. Results: All the 55 samples collected from diabetic foot ulcers were positive. We isolated 64 bacterial strains (some samples were positive for 2 microorganisms). The most frequently isolated germ was S. aureus, in 33 samples (51.56%). All these S. aureus strains showed resistance to benzylpenicillin, while only 33.33% were methicillin-resistant (MRSA). Conclusions: The most frequently isolated germ in the wound secretions from diabetic foot ulcers was S. aureus. The highest percentage of antimicrobial resistance was recorded to benzylpenicillin and erythromycin.

Blind Comparative study between Silver nanoparticles dressings and Standard Moist Wound Dressings (SMWD) in management of diabetic foot ulcers

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Amr Abdelaal ◽  
Mostafa Soliman ◽  
Hany Rafik ◽  
Mohamed Emam ◽  
Mohamed Mahmoud Mohamed Elsadek
Keyword(s):  
Silver Nanoparticles ◽  
Diabetic Foot ◽  
Wound Dressing ◽  
Treatment Modalities ◽  
Controlled Study ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Group A ◽  
Group B

Abstract Background Diabetic foot ulcers (DFUs) are the main cause of hospitalization in diabetic patients and they are considered a major worldwide health problem. Thus, there is a need to evaluate various treatment modalities. In this study we will assess the clinical efficacy of Silver nanoparticles dressing vs Standard Moist Wound Dressing (SMWD) in management of diabetic foot ulcers. Objective To compare wound outcome, limb salvage, healing time of diabetes related foot ulcers and cost effectiveness in terms of duration of hospital stay between Silver nanotechnology dressings and Standard moist wound therapy (SMWT) in management of diabetic foot ulcers. Patients and Methods This is a prospective randomized controlled study involving 34 patients with active diabetic foot ulcers, in a high volume tertiary referral vascular center. They were divided into 2 groups: 17 patients (group A) were prescribed SMWD and the other 17 patients (group B) received Silver nanoparticles wound dressing. Results Our study correlates with the study conducted by K.Suhas et al. which had observed that Silver nanoparticles wound dressing was safe and effective treatment for complex diabetic foot wounds and could lead to higher proportion of healed wounds and faster healing rates. At the end of the study, group B promised a better outcome as compared to group A. Conclusion The role of Silver nanoparticles wound dressing in healing of diabetic foot ulcers has been proposed as a novel method of manipulating the chronic wound environment in a way that it reduces bacterial burden and chronic interstitial wound fluid, increases vascularity and cytokine expression and to an extent mechanically exploiting the viscoelasticity of peri wound tissues.

Association of traditional complementary and alternate medicine usage with quality of life of diabetic patients in a Malaysian tertiary hospital

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Chinedum Ogbonnaya Eleazu ◽  
Aniza Abd Aziz ◽  
Tay Chuu Suen ◽  
Lam Chun-Hau ◽  
Chin Elynn ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Diabetic Foot ◽  
Heart Diseases ◽  
Tertiary Hospital ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Content Type ◽  
Significant Difference

Purpose This study aims to design to assess the traditional, complementary and alternate medicine (TCAM) usage and its association with the quality of life (QOL) of Type 2 diabetic patients in a tertiary hospital (Hospital Universiti Sains Malaysia) in Malaysia. Design/methodology/approach A total of 300 respondents included in this study were divided into the following two major categories: TCAM (34.33% of respondents) and non-TCAM users (65.67% of the respondents), respectively. The mean ages of the respondents were 59.3 ± 10.2 for the TCAM users and 57.7 ± 12.0 for the non-TCAM users. Findings A greater percentage of non-TCAM users reported poor control of diabetes (14.7%) and blood glucose (55.8%) compared with the TCAM users (9.7% and 48.5%, respectively). Further, the diabetic patients on TCAM reported lower rates of coma, stroke and kidney problems but higher rates of diabetic foot ulcers, heart diseases and retinopathy than the non-TCAM users. Additionally, the diabetic patients with TCAM usage had a significantly better physical (p = 0.02) and overall (p = 0.03) qualities of life compared to the non-TCAM users. However, psychological, social and environmental health did not show any significant difference. Originality/value The prevalence of TCAM usage among diabetic patients was lower than in other comparable studies. Diabetic patients on TCAM reported lower rates of coma, stroke and kidney problems but higher rates of diabetic foot ulcers, heart diseases and retinopathy than the non-TCAM users. Further, diabetes patients on TCAM reported better QOL compared to non-TCAM users especially in terms of physical health.

Identification and Drug Sensitivity of Aerobic Bacterial Isolates from Diabetic Foot Ulcers of Sudanese Patients: a Cross sectional study

2020 ◽  
Author(s):  
saada Mohamed nour ◽  
Maowia Mukhtar ◽  
Mohamed Elmakk ◽  
Elshibli Mohamed Elshibli ◽  
Walyeldin Elnour Elfakey ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Diffusion Method ◽  
Foot Ulcers ◽  
Aerobic Bacteria ◽  
Diabetic Patients ◽  
Gram Negative Bacteria ◽  
Female Ratio ◽  
Gram Negative ◽  
The Mean ◽  
Grade 3

Abstract Background Diabetic foot ulcer infection cause great morbidity and mortality among diabetic patients and is a major cause of lower extremity amputation worldwide. This study aimed to determine the profile of aerobic bacteria and their antibiotic sensitivity patterns in diabetic foot infections (DFI) among different Wagner's grades. Methods This study was conducted during December 2017 - March 2018 in a Diabetic Center, Sudan. A total of 152 diabetic patients with different grades of foot ulcers were randomly enrolled in the study. The patients were grouped using Wagner's classification. Tissue biopsies and deep swabs were collected from the ulcers for aerobic cultures. The cultured isolates were identified using phenotypic and biochemical properties and their sensitivity to commonly used antibiotics, Colistin, Aikacin, Ciprofloxacin, Augmentin, Ceftazideme, Gentamicin, Clindamycin, Ceftriaxone Meropenum. Cotrimoxazole, Erythomycin, Oxacillin and Vancomycin. Fusidic acid, Imepenem, and Piperacillin was tested using the Kirby Bauer disk diffusion method. Results The mean age of the patients was 54.31 (SD ± 12.1) years, male to female ratio of 8: 1. The mean duration of diabetes was 14 (SD ± 8) years. The ulcers varied in duration from 1 day to 10 years. of 152 samples 181 aerobic bacteria were isolated. Cultures yielded 1-3 isolate per culture. The maximum number was isolated from grade 3 group followed by long standing ulcer LSU group 50.8% and 28% respectively. Polymicrobial infection was higher in LSU (30.4%). The isolates were mostly Gram-negative bacteria. The most frequent were proteus spp. (35.3%), S. aureus MRSA 14.4% and Coliform 12.2% respectively. The most common isolates in grade 3 were P. Mirablis, Staphylococcus and Coliform and in long standing ulcers were P. Mirablis, S. aureus MRSA and Coagulase negative staphylococcus respectively. Conclusion Gram-negative bacteria were more prevalent and the most frequent pathogens were Proteus spp. The most common polymicrobial infections were due to P. mirablis with; P. aerginosa, S. MRSA and Coliform respectively . Gram negative rods were sensitive to Amikacin, (80.6) %) while the highest sensitivity of Gram positive was to Imepnem (85%). Most of the isolates were sensitive to Meropenem. No significant relation between Wagner grades and neuropathy was detected.

scholarly journals Understanding the relationship between depression and diabetic foot ulcers

2016 ◽  
Vol 04 (01) ◽  
pp. 017-024 ◽  
Author(s):  
Andrew Steel ◽  
John Reece ◽  
Anne-Marie Daw
Keyword(s):  
Depressive Symptoms ◽  
Diabetic Foot ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Biological Relationship ◽  
The Cost ◽  
The Impact ◽  
Concept Review ◽  
The Relationship

AbstractThe prevalence of diabetes is increasing, as is the cost of managing its comorbidities. Diabetic foot ulcers (DFUs) and their complications place a considerable cost burden on the health system, and lead to a significant level of disability. The relationship between depression and diabetes is well-established. The relationship between depression and foot ulcers in diabetic patients is less well-established. The purpose of this article is to provide a current concept review of the literature from 1988 to 2013, linking DFUs and depressive symptoms, with an emphasis on the impact depressive symptoms have on healing rates of DFUs. Articles specifically focusing on the biological relationship, depression′s impact on self-care, screening for depressive symptoms, causes and cost of treating DFUs, and measuring depression were reviewed. A deeper understanding of this relationship is needed to identify causal relationships, improve treatment outcomes, and reduce healing times of DFUs.

scholarly journals The Role of Recombinant Proteins and Growth Factors in the Management of Diabetic Foot Ulcers: A Systematic Review of Randomized Controlled Trials

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Elahe Mahdipour ◽  
Amirhossein Sahebkar
Keyword(s):  
Systematic Review ◽  
Growth Factors ◽  
Growth Factor ◽  
Recombinant Proteins ◽  
Diabetic Foot ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Diabetic Foot Ulcers ◽  
Randomized Controlled

Background. Recombinant proteins and growth factors are emerging therapies for diabetic foot ulcers. Despite several clinical reports, there has been no comprehensive and systematic assessment of the totality of clinical evidence on the efficacy and safety of recombinant proteins and growth factors in diabetic foot ulcers. We tried to address this gap through an updated systematic review of randomized controlled trials (RCTs). Methods. PubMed, the Cochrane Library, Scopus, Embase, and Google Scholar databases were searched, and RCTs on the efficacy of recombinant proteins and growth factors in the treatment of cutaneous wounds in diabetic patients were selected. The literature search and assessment were performed by two independent reviewers. Methodological quality of studies was appraised using the Jadad scale. Results. We identified 26 RCTs involving diabetic patients with ulcer that evaluated the effectiveness of platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, erythropoietin, transforming growth factor, talactoferrin, and rusalatide acetate. The main primary outcome was complete healing though different indices were employed to define this such as wound closure, granulation tissue formation, or complete reepithelialization. Few studies had a follow-up period to report any recurrence and amputation rate. No adverse effect was reported due to the intervention. Conclusion. Overall, there is a greater agreement on the effectiveness of EGF to enhance the healing of diabetic ulcers. Nevertheless, extant evidence is lacking for other agents since few trials have been conducted for most of the growth factors and available studies are heterogeneous in their methodologies.

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