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1.
BMC Health Serv Res ; 24(1): 101, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38238697

ABSTRACT

BACKGROUND: Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a disproportionate burden of rural infections. To reverse growing infection rates, the state must increase its focus on prevention efforts, including novel strategies. One such approach is to utilize dashboards that visualize real-time data on the pre-exposure prophylaxis (PrEP) care continuum to assist in prioritizing evidence-based preventative care for those most vulnerable for HIV infection. METHODS: We conducted a mixed methods evaluation to ascertain stakeholders' perceptions on the acceptability, feasibility, appropriateness, and usability of a PrEP care continuum dashboard, as well as gain insight on ways to improve the activities necessary to sustain it. Clinicians, administrators, and data personnel from participating sites in Alabama completed surveys (n = 9) and participated in key informant interviews (n = 10) to better understand their experiences with the prototype data dashboard and to share feedback on how it can be modified to best fit their needs. RESULTS: Surveys and interviews revealed that all participants find the pilot data dashboard to be an acceptable, feasible, and appropriate intervention for clinic use. Overall, stakeholders find the pilot dashboard to be usable and helpful in administrative efforts, such as report and grant writing; however, additional refining is needed in order to reduce burden and optimize usefulness. Participants voiced concerns about their site's abilities to sustain the dashboard, including the lack of systematized PrEP protocols and limited funds and staff time dedicated to PrEP data collection, cleaning, and upload. CONCLUSION: Study participants from clinics providing HIV prevention services, including PrEP, in Alabama voiced interest in sustaining and refining a data dashboard that tracks clients across the PrEP care continuum. Despite viewing the platform itself as an acceptable, feasible, and appropriate intervention, participants agreed that efforts need to be focused on standardizing PrEP data collection protocols in order to ensure consistent, accurate data capture and that limited funds and staff time are barriers to the sustained implementation of the dashboard in practice.


Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Humans , HIV Infections/prevention & control , HIV Infections/drug therapy , Feasibility Studies , Anti-HIV Agents/therapeutic use , Acquired Immunodeficiency Syndrome/drug therapy , Southeastern United States , Pre-Exposure Prophylaxis/methods
2.
J Bacteriol ; 205(9): e0013823, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37655912

ABSTRACT

Short-chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as maintenance of the intestinal barrier, cell signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including its importance in alleviating infections caused by pathogens such as Clostridioides difficile. Despite the potential role of SCFAs in mitigating C. difficile infection, their direct effect on C. difficile remains unclear. Through a set of in vitro experiments, we investigated how SCFAs influence C. difficile growth, sporulation, and toxin production. Similar to previous studies, we observed that butyrate decreased growth of C. difficile strain 630 in a dose-dependent manner. The presence of butyrate also increased C. difficile sporulation, with minimal increases in toxin production. RNA-Seq analysis validated our experimental results, demonstrating increased expression of sporulation-related genes in conjunction with changes in metabolic and regulatory genes, such as a putative carbon starvation protein, CstA. Collectively, these data suggest that butyrate may induce alternative C. difficile survival pathways, modifying its growth ability and virulence to persist in the gut environment. IMPORTANCE Several studies suggest that butyrate may modulate gut infections, such as reducing inflammation caused by the healthcare-associated Clostridioides difficile. While studies in both animal models and human studies correlate high levels of butyrate with reduced C. difficile burden, the direct impact of butyrate on C. difficile remains unclear. Our study demonstrates that butyrate directly influences C. difficile by increasing its sporulation and modifying its metabolism, potentially using butyrate as a biomarker to shift survival strategies in a changing gut environment. These data point to additional therapeutic approaches to combat C. difficile in a butyrate-directed manner.


Subject(s)
Clostridioides difficile , Clostridium Infections , Animals , Humans , Butyrates/metabolism , Clostridioides/metabolism , Clostridioides difficile/genetics , Fermentation , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Clostridium Infections/microbiology
3.
J Acquir Immune Defic Syndr ; 94(2S): S99-S107, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37707856

ABSTRACT

BACKGROUND: Using the Asset Bundle Model, we sought to understand the social support assets and needs of underrepresented minority (URM) high school, undergraduate, and graduate students. SETTING: Study participants were or had participated in health sciences pathway programs at Birmingham City Schools and/or the University of Alabama at Birmingham. METHODS: We took a concurrent mixed methods approach to conduct an environmental scan of health science pathway programs in the Birmingham, AL area. Four focus groups were conducted between November 2022 and January 2023, and a 225-item online survey was administered between November 4, 2022, and February 4, 2023. Both tools collected data from high school, undergraduate, and graduate students to examine key components of existing health care pathways programs for URMs and identify barriers and facilitators to successful implementation of such programs. RESULTS: Twenty-two students participated in the focus groups, and 168 individuals responded to the survey. Both focus group participants and interview respondents were primarily URMs (eg, 68.2% and 65.7% identified as Black or African American, respectively). Survey responses and focus group discussions showed that, overall, undergraduate and graduate students programs develop more robust identities as future health care professionals through friendships and institutional supports, expand their networks more broadly through mentorship, and feel more supported by family members in their academic endeavors than high school students. CONCLUSIONS: Health science pathway programs for URMs should facilitate and bolster social supports for students, especially those in high school, to enhance persistence through education and into the workforce.


Subject(s)
HIV Infections , Humans , Alabama , Students , Educational Status , Social Support
4.
bioRxiv ; 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37163089

ABSTRACT

Short chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as the intestinal barrier, signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including importance in combatting infections caused by pathogens such as Clostridioides difficile . Despite the potential role of SCFAs in mitigating C. difficile infection, their direct effect on C. difficile remains unclear. Through a set of in vitro experiments, we investigated how SCFAs influence C. difficile growth, sporulation, and toxin production. Similar to previous studies, we observed that butyrate decreased growth of C. difficile strain 630 in a dose-dependent manner. The presence of butyrate also increased C. difficile sporulation, with minimal increases in toxin production. RNA-Seq analysis validated our experimental results, demonstrating increased expression of sporulation-related genes in conjunction with alternative metabolic and related C. difficile regulatory pathways, such as the carbon catabolite repressor, CcpA. Collectively, these data suggest that butyrate may signal alternative C. difficile metabolic pathways, thus modifying its growth and virulence to persist in the gut environment. IMPORTANCE: Several studies suggest that butyrate may be important in alleviating gut infections, such as reducing inflammation caused by the healthcare-associated Clostridioides difficile . While studies in both animal models and human studies correlate high levels of butyrate with reduced C. difficile burden, the direct impact of butyrate on C. difficile remains unclear. Our study demonstrates that butyrate directly influences C. difficile by increasing its sporulation and modifying its metabolism, potentially using butyrate as a biomarker to shift survival strategies in a changing gut environment. These data point to additional therapeutic approaches to combat C. difficile in a butyrate-directed manner.

5.
Drug Alcohol Depend ; 244: 109777, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36680808

ABSTRACT

INTRODUCTION: Buprenorphine can only be prescribed for opioid use disorder (OUD) by providers with a Controlled Substance Act waiver (X waiver) from the Substance Abuse and Mental Health Services Administration. This study examines what motivates physicians to become X waivered, as well as what facilitates and hinders physicians' abilities to prescribe buprenorphine to people with OUD. METHODS: This is a qualitative study of physicians in Birmingham, Alabama. We recruited physicians from the University of Alabama at Birmingham and Cahaba Medical Care to participate in semi-structured interviews and used a Framework-guided Rapid Qualitative Analysis technique to analyze the transcripts for themes aligned with the Social Cognitive Theory. RESULTS: A total of 27 physicians were interviewed between December 15th, 2021 and July 21st, 2022. The vast majority reported seeking to obtain an X waiver when their employers encouraged or mandated it. Most providers reported being eager to become waivered when first asked by their employers, while a few described some hesitancies. Essentially all participants agreed that having mentors is important when first prescribing buprenorphine and that support from social workers and counselors is needed. Most physicians discussed how stigma, administrative barriers, and a lack of community resources hinder buprenorphine prescription. CONCLUSIONS: Our findings suggest that employers are effective in encouraging X waiver certification and mentors and allied health professionals are important in ensuring providers continue buprenorphine prescription. Additionally, it is critical to address challenges to successful buprenorphine prescription, like stigma and administrative barriers.


Subject(s)
Buprenorphine , Opioid-Related Disorders , Physicians , Humans , Buprenorphine/therapeutic use , Opiate Substitution Treatment , Motivation , Practice Patterns, Physicians' , Opioid-Related Disorders/drug therapy , Drug Prescriptions
6.
Ann Vasc Surg ; 91: 168-175, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36563846

ABSTRACT

BACKGROUND: Stenosis severity has been the indication for carotid endarterectomy (CEA) for 4 decades, but the annual stroke risk in asymptomatic carotid stenosis >70% is under 2%. Atherosclerotic volume has emerged as a risk factor for future stroke, but needs to be measured noninvasively. Tomographic ultrasound (tUS) is a novel technology that assembles 3D images in seconds. We evaluated accuracy of measuring Carotid Plaque Volume (CPV) with tUS in patients undergoing CEA. METHOD: Consecutive patients were imaged immediately before CEA by tUS and contrast-enhanced tUS (CEtUS). CPV was measured using tUS, CEtUS, and a fused images incorporating both tUS and CEtUS by trained vascular scientists. Precise volume of the endarterectomy specimen was measured using Archimedes technique. RESULTS: Mean ± sd (range) CPV in 129 endarterectomy specimens was 0.75 ± 0.43 cm3 (0.10-2.47 cm3). Mean ± sd CPV measured by tUS (n = 114) was 0.87 ± 0.51 cm3, CEtUS (n = 104) was 0.75 ± 0.45 cm3 and with fusion (n = 95) was 0.83 ± 0.49 cm3. Differences between specimen volume and CPV measured by tUS (0.13 ± 0.24 cm3), CEtUS (-0.01 ± 0.21 cm3) or fusion (-0.08 ± 0.20) were clinically insignificant. Intra-/interobserver differences were minimal. CONCLUSIONS: tUS accurately measures CPV with excellent intra-/interobserver agreement. CEtUS improves accuracy if precise CPV measurement is needed for research but tUS alone would be sufficient for population screening.


Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Plaque, Atherosclerotic , Stroke , Humans , Feasibility Studies , Treatment Outcome , Carotid Arteries , Ultrasonography/methods , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Carotid Stenosis/complications , Endarterectomy, Carotid/adverse effects , Plaque, Atherosclerotic/complications , Stroke/etiology , Contrast Media
7.
Rheumatol Int ; 41(6): 1089-1096, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32797279

ABSTRACT

Objective methods are needed to quantify digital artery disease in systemic sclerosis (SSc) for clinical trials of vascular therapies. Our primary aim was to examine feasibility of a novel tomographic three-dimensional-(3-D) ultrasound (tUS) with high-frequency ultrasound (HFUS) or ultra-high-frequency ultrasound (UHFUS) to assess the digital arteries in patients with SSc compared to healthy controls. A secondary objective was to compare the total wall volume (TWV) as a measure of intimal/medial thickness. Eighteen patients with a confirmed diagnosis of SSc were studied by tUS HFUS (17.5 MHz, n = 10) or tUS UHFUS (48 and 70 MHz, n = 8) with equal numbers of healthy controls of similar age and gender. The majority of patients had limited cutaneous SSc and were representative of a spectrum of digital vasculopathy, with over half (n = 6 HFUS and n = 5 UHFUS) having previous digital ulceration. Over half were receiving oral vasodilatory therapy. TWV was measured in both digital arteries of the middle finger bilaterally. At least, two digital arteries could be identified at 17.5 MHz in all patients and healthy controls. Whereas, at least two digital arteries could be identified in relatively fewer patients compared to healthy controls using 48 MHz (n = 6 and 10) and especially 70 MHz (n = 4 and 10) UHFUS. The median difference in TWV between patients and healthy controls was -6.49 mm3 using 17.5 MHz, 1.9 mm3 at 48 MHz, and -0.4 mm3 at 70 MHz. tUS using UHFUS is a feasible method to measure TWV of digital arteries in SSc. Transducer frequency plays an important factor in successful digital artery measurement, with 48 MHz being the optimal frequency.


Subject(s)
Arteries/diagnostic imaging , Fingers/blood supply , Scleroderma, Systemic/complications , Aged , Case-Control Studies , Cross-Sectional Studies , Female , Fingers/diagnostic imaging , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Scleroderma, Systemic/physiopathology , Tomography, X-Ray Computed , Ultrasonography
8.
Br J Anaesth ; 120(3): 509-516, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29452807

ABSTRACT

BACKGROUND: The Sepsis-3 guidelines diagnose sepsis based on organ dysfunction in patients with either proven or suspected infection. The objective of this study was to assess the incidence and outcomes of sepsis diagnosed using these guidelines in patients in a cardiac intensive care unit (CICU) after cardiac surgery. METHODS: Daily sequential organ failure assessment (SOFA) scores were calculated for 2230 consecutive adult cardiac surgery patients between January 2013 and May 2015. Patients with an increase in SOFA score of ≥2 and suspected or proven infection were identified. The length of CICU stay, 30-day mortality and 2-yr survival were compared between groups. Multivariable linear regression, multivariable logistic regression, and Cox proportional hazards regression were used to adjust for possible confounders. RESULTS: Sepsis with suspected or proven infection was diagnosed in 104 (4.7%) and 107 (4.8%) patients, respectively. After adjustment for confounding variables, sepsis with suspected infection was associated with an increased length of CICU stay of 134.1h (95% confidence interval (CI) 99.0-168.2, P<0.01) and increased 30-day mortality risk (odds ratio 3.7, 95% CI 1.1-10.2, P=0.02). Sepsis with proven infection was associated with an increased length of CICU stay of 266.1h (95% CI 231.6-300.7, P<0.01) and increased 30-day mortality risk (odds ratio 6.6, 95% CI 2.6-15.7, P<0.01). CONCLUSIONS: Approximately half of sepsis diagnoses were based on proven infection and half on suspected infection. Patients diagnosed with sepsis using the Sepsis-3 guidelines have significantly worse outcomes after cardiac surgery. The Sepsis-3 guidelines are a potentially useful tool in the management of sepsis following cardiac surgery.


Subject(s)
Cardiac Surgical Procedures , Patient Outcome Assessment , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Sepsis/diagnosis , Sepsis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Critical Care/methods , Female , Hospital Mortality , Humans , Incidence , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , Postoperative Complications/therapy , Practice Guidelines as Topic , Sepsis/therapy , Survival Analysis , Young Adult
9.
Br J Surg ; 105(3): 262-269, 2018 02.
Article in English | MEDLINE | ID: mdl-29315509

ABSTRACT

BACKGROUND: The main indication for carotid endarterectomy (CEA) is severity of carotid artery stenosis, even though most strokes in carotid disease are embolic. The relationship between carotid plaque volume (CPV) and symptoms of cerebral ischaemia, and the measurement of CPV by minimally invasive tomographic ultrasound imaging, were investigated. METHODS: The volume of the endarterectomy specimen was measured using a validated saline suspension technique in patients undergoing CEA. Time from last symptom and severity of stenosis measured by duplex ultrasonography were recorded. Middle cerebral artery emboli were counted using transcranial Doppler imaging (TCD) in a subset of patients. RESULTS: Some 339 patients were included, 270 with symptomatic and 69 with asymptomatic carotid stenosis. Mean(s.d.) CPV was higher in symptomatic than in asymptomatic patients (0·97(0·43) versus 0.74(0·41) cm3 ; P < 0·001). CPV did not correlate with severity of carotid stenosis (P = 0·770). Mean CPV was highest at 1·03(0·46) cm3 in the 4 weeks following cerebral symptoms, declining to 0·78(0·36) cm3 beyond 8 weeks. Among 33 patients who had TCD, mean CPV was 1·00(0·48) cm3 in the 27 patients with ipsilateral cerebral emboli compared with 0·67(0·16) cm3 in those without (P = 0·142). There was excellent correlation between CPV measured by tomographic ultrasound imaging and the endarterectomy specimen in 34 patients (r = 0·93, P < 0·001). CONCLUSION: CPV correlated with symptoms of cerebral ischaemia, but not carotid stenosis. It could be a potential indicator for CEA.


Subject(s)
Carotid Stenosis/pathology , Endarterectomy, Carotid , Plaque, Atherosclerotic/pathology , Severity of Illness Index , Adult , Aged , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/etiology , Carotid Stenosis/surgery , Female , Humans , Male , Middle Aged , Observer Variation , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/surgery , Ultrasonography
10.
Eur J Vasc Endovasc Surg ; 52(4): 466-474, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27436173

ABSTRACT

Three-dimensional (3D) ultrasound is an evolving modality that may have numerous applications in the management of abdominal aortic aneurysms. Many vascular specialists will not be familiar with the different ways in which 3D vascular ultrasound data can be acquired nor how potential applications are being explored by researchers. Most of the current literature consists of small series and single-centre experience, although clinical themes such as measurement of abdominal aortic aneurysm volume and surveillance following endovascular repair are emerging. The aim of this topical review is to introduce clinicians to the current concepts of 3D ultrasound, review the current literature, and highlight avenues for further research in this new and exciting field of vascular imaging.


Subject(s)
Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Imaging, Three-Dimensional/methods , Ultrasonography/methods , Aorta, Abdominal/diagnostic imaging , Endovascular Procedures/methods , Humans , Postoperative Complications/diagnostic imaging
11.
Eur J Vasc Endovasc Surg ; 51(2): 225-31, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26497254

ABSTRACT

OBJECTIVE: There remains a population of patients with aortic aneurysms that cannot be treated by conventional endovascular means. Multi-layer flow modulating stents (MFMS) are a novel approach for the treatment of aortic aneurysm; this study reports outcomes of a UK pilot study of first-generation MFMS in thoraco-abdominal (TAAA) and perirenal aneurysms (PAA) in patients who were also unfit for open surgery. METHODS: Patients with TAAA and PAA unfit for open surgery and with no conventional options for endovascular repair were recruited. Follow-up included CTA at 1, 3, 6, and 12 months, then annually. Outcome measures included 30 day mortality, growth-free survival, branch vessel patency, complications, re-intervention, and maximal aortic diameter. RESULTS: MFMS were implanted in 14 patients (6 PAA, 8 TAAA) between October 2011 and March 2014 with one (7%) 30 day death and 11 (79%) surviving to 12 months. The median aneurysm growth was 9 mm in the first 12 months following implantation. On mean follow-up of 22.8 months, seven (50%) patients had died including one confirmed rupture. AAA diameter remained stable in only two of the surviving patients. Fifty of 51 covered aortic branches remained patent with no embolic episodes or symptoms of ischaemia in any patient. MFMS dislocation occurred in four patients, leading to re-intervention in two. A total of six re-interventions were performed in five patients (35%) with one post-re-intervention death. CONCLUSION: These first-generation MFMS were unstable and dislocated frequently. It is uncertain whether MFMS implantation influenced the natural history of these aneurysms as none decreased in size, but two remain stable after a mean of 22.8 months. Although side branch patency was maintained, our results do not support the continued use of these first-generation devices. Further development is needed if this technology is to have a role in treatment of aortic aneurysm.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/instrumentation , Stents , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Abdominal/physiopathology , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/mortality , Aortic Aneurysm, Thoracic/physiopathology , Aortic Rupture/etiology , Aortic Rupture/therapy , Aortography/methods , Blood Flow Velocity , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , England , Female , Foreign-Body Migration/etiology , Foreign-Body Migration/therapy , Humans , Male , Middle Aged , Pilot Projects , Prosthesis Design , Regional Blood Flow , Retreatment , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Vascular Patency
12.
Clin Appl Thromb Hemost ; 21(5): 420-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25748178

ABSTRACT

UNLABELLED: Venous thromboembolism (VTE) during chemotherapy is common, with 7% mortality in metastatic breast cancer (MBC). In a prospective cohort study of patients with breast cancer, we investigated whether vascular endothelial cell activation (VECA), and whether apoptosis, is the cause of chemotherapy-induced VTE. METHODS: Serum markers of VECA, E-selectin (E-sel), vascular cell adhesion molecule 1 (VCAM-1) and d-dimer (fibrin degradation and hypercoagulability marker) were measured prechemotherapy and at 1, 4, and 8 days following chemotherapy. Clinical deep vein thrombosis (DVT) or pulmonary embolism and occult DVT detected by duplex ultrasound imaging were recorded as VTE-positive (VTE+). In patients with MBC, hypercoagulable response to chemotherapy was compared between patients with and without cancer progression. Development of VTE and cancer progression was assessed 3 months following starting chemotherapy. RESULTS: Of the 134 patients, 10 (7.5%) developed VTE (6 [17%] of 36 MBC receiving palliation, 0 of 11 receiving neoadjuvant to downsize tumor, and 4 [5%] of 87 early breast cancer receiving adjuvant chemotherapy, P = .06). Levels of E-sel and VCAM-1 decreased in response to chemotherapy (P < .001) in both VTE+ and patients not developing VTE (VTE-). However, decrease in VECA markers was similar in VTE+ and VTE- patients, implying this is not the cause of VTE. In patients with MBC following chemotherapy, d-dimer (geometric mean) increased by 36% in the 21 patients with MBC responding to chemotherapy but steadily decreased by 11% in the 15 who progressed (day 4, P < .01), implying patients with tumor response (apoptosis) had an early hypercoagulable response. CONCLUSIONS: During chemotherapy for breast cancer, VECA is induced; however, this is not the primary mechanism for VTE. Chemotherapy-induced apoptosis may enhance hypercoagulability and initiate VTE.


Subject(s)
Breast Neoplasms/complications , Induction Chemotherapy/methods , Thrombophilia/complications , Venous Thromboembolism/chemically induced , Adult , Aged , Apoptosis , Cohort Studies , Endothelial Cells , Female , Humans , Middle Aged , Neoplasm Metastasis , Prospective Studies
13.
Br J Anaesth ; 114(3): 430-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25481223

ABSTRACT

BACKGROUND: Cardiopulmonary exercise testing (CPET) is increasingly used in the preoperative assessment of patients undergoing major surgery. The objective of this study was to investigate whether CPET can identify patients at risk of reduced survival after abdominal aortic aneurysm (AAA) repair. METHODS: Prospectively collected data from consecutive patients who underwent CPET before elective open or endovascular AAA repair  (EVAR) at two tertiary vascular centres between January 2007 and October 2012 were analysed. A symptom-limited maximal CPET was performed on each patient. Multivariable Cox proportional hazards regression modelling was used to identify risk factors associated with reduced survival. RESULTS: The study included 506 patients with a mean age of 73.4 (range 44-90). The majority (82.6%) were men and most (64.6%) underwent EVAR. The in-hospital mortality was 2.6%. The median follow-up was 26 months. The 3-year survival for patients with zero or one sub-threshold CPET value ([Formula: see text] at AT<10.2 ml kg(-1) min(-1), peak [Formula: see text]<15 ml kg(-1) min(-1) or [Formula: see text] at AT>42) was 86.4% compared with 59.9% for patients with three sub-threshold CPET values. Risk factors independently associated with survival were female sex [hazard ratio (HR)=0.44, 95% confidence interval (CI) 0.22-0.85, P=0.015], diabetes (HR=1.95, 95% CI 1.04-3.69, P=0.039), preoperative statins (HR=0.58, 95% CI 0.38-0.90, P=0.016), haemoglobin g dl(-1) (HR=0.84, 95% CI 0.74-0.95, P=0.006), peak [Formula: see text]<15 ml kg(-1) min(-1) (HR=1.63, 95% CI 1.01-2.63, P=0.046), and [Formula: see text] at AT>42 (HR=1.68, 95% CI 1.00-2.80, P=0.049). CONCLUSIONS: CPET variables are independent predictors of reduced survival after elective AAA repair and can identify a cohort of patients with reduced survival at 3 years post-procedure. CPET is a potentially useful adjunct for clinical decision-making in patients with AAA.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Elective Surgical Procedures/mortality , Exercise Test/methods , Exercise Test/statistics & numerical data , Preoperative Care/methods , Vascular Surgical Procedures/mortality , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Elective Surgical Procedures/methods , Elective Surgical Procedures/statistics & numerical data , Endovascular Procedures/methods , Endovascular Procedures/mortality , Endovascular Procedures/statistics & numerical data , Female , Follow-Up Studies , Hospital Mortality , Humans , Male , Middle Aged , Preoperative Care/statistics & numerical data , Proportional Hazards Models , Prospective Studies , Reproducibility of Results , Risk Assessment , Risk Factors , Survival Analysis , Vascular Surgical Procedures/methods , Vascular Surgical Procedures/statistics & numerical data
14.
Bone Joint J ; 96-B(8): 1062-9, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25086122

ABSTRACT

In this randomised controlled trial, we evaluated the role of elastic compression using ankle injury stockings (AIS) in the management of fractures of the ankle. A total of 90 patients with a mean age of 47 years (16 to 79) were treated within 72 hours of presentation with a fracture of the ankle, 31 of whom were treated operatively and 59 conservatively, were randomised to be treated either with compression by AIS plus an Aircast boot or Tubigrip plus an Aircast boot. Male to female ratio was 36:54. The primary outcome measure was the functional Olerud-Molander ankle score (OMAS). The secondary outcome measures were; the American Orthopaedic Foot and Ankle Society score (AOFAS); the Short Form (SF)-12v2 Quality of Life score; and the frequency of deep vein thrombosis (DVT). Compression using AIS reduced swelling of the ankle at all time points and improved the mean OMAS score at six months to 98 (95% confidence interval (CI) 96 to 99) compared with a mean of 67 (95% CI 62 to 73) for the Tubigrip group (p < 0.001). The mean AOFAS and SF-12v2 scores at six months were also significantly improved by compression. Of 86 patients with duplex imaging at four weeks, five (12%) of 43 in the AIS group and ten (23%) of 43 in the Tubigrip group developed a DVT (p = 0.26). Compression improved functional outcome and quality of life following fracture of the ankle. DVTs were frequent, but a larger study would be needed to confirm that compression with AISs reduces the incidence of DVT.


Subject(s)
Ankle Injuries/therapy , Fractures, Bone/therapy , Stockings, Compression , Activities of Daily Living , Adolescent , Adult , Aged , Aged, 80 and over , Ankle Injuries/physiopathology , Ankle Injuries/rehabilitation , Ankle Injuries/surgery , Female , Fractures, Bone/physiopathology , Fractures, Bone/rehabilitation , Fractures, Bone/surgery , Humans , Male , Middle Aged , Postoperative Complications/prevention & control , Postoperative Complications/rehabilitation , Quality of Life , Range of Motion, Articular/physiology , Recovery of Function , Single-Blind Method , Treatment Outcome , Venous Thrombosis/prevention & control , Young Adult
15.
Reprod Toxicol ; 48: 51-61, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24907688

ABSTRACT

Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we evaluated a quantitative assay in transgenic zebrafish using angiogenesis inhibitors that target VEGFR2 (PTK787) or EGFR (AG1478). Both PTK787 and AG1478 exposure impaired intersegmental vessel (ISV) sprouting, while AG1478 also produced caudal and pectoral fin defects at concentrations below those necessary to blunt ISV morphogenesis. The functional consequences of vessel toxicity during early development included decreased body length and survival in juvenile cohorts developmentally exposed to inhibitor concentrations sufficient to completely block ISV sprouting angiogenesis. These data show that concentration-dependent disruption of the presumed targets for these inhibitors produce adverse outcomes at advanced life stages.


Subject(s)
Blood Vessels/embryology , Embryo, Nonmammalian/embryology , ErbB Receptors/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Zebrafish/embryology , Angiogenesis Inhibitors/pharmacology , Animals , Animals, Genetically Modified , Blood Vessels/drug effects , Embryo, Nonmammalian/drug effects , Embryonic Development/drug effects , Embryonic Development/physiology , Phthalazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Quinazolines/pharmacology , Tyrphostins/pharmacology
16.
Eur J Vasc Endovasc Surg ; 48(1): 38-44, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24837173

ABSTRACT

OBJECTIVE/BACKGROUND: A number of contemporary risk prediction models for mortality following elective abdominal aortic aneurysm (AAA) repair have been developed. Before a model is used either in clinical practice or to risk-adjust surgical outcome data it is important that its performance is assessed in external validation studies. METHODS: The British Aneurysm Repair (BAR) score, Medicare, and Vascular Governance North West (VGNW) models were validated using an independent prospectively collected sample of multicentre clinical audit data. Consecutive, data on 1,124 patients undergoing elective AAA repair at 17 hospitals in the north-west of England and Wales between April 2011 and March 2013 were analysed. The outcome measure was in-hospital mortality. Model calibration (observed to expected ratio with chi-square test, calibration plots, calibration intercept and slope) and discrimination (area under receiver operating characteristic curve [AUC]) were assessed in the overall cohort and procedural subgroups. RESULTS: The mean age of the population was 74.4 years (SD 7.7); 193 (17.2%) patients were women and the majority of patients (759, 67.5%) underwent endovascular aneurysm repair. All three models demonstrated good calibration in the overall cohort and procedural subgroups. Overall discrimination was excellent for the BAR score (AUC 0.83, 95% confidence interval [CI] 0.76-0.89), and acceptable for the Medicare and VGNW models, with AUCs of 0.78 (95% CI 0.70-0.86) and 0.75 (95% CI 0.65-0.84) respectively. Only the BAR score demonstrated good discrimination in procedural subgroups. CONCLUSION: All three models demonstrated good calibration and discrimination for the prediction of in-hospital mortality following elective AAA repair and are potentially useful. The BAR score has a number of advantages, which include being developed on the most contemporaneous data, excellent overall discrimination, and good performance in procedural subgroups. Regular model validations and recalibration will be essential.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/mortality , Decision Support Techniques , Endovascular Procedures/mortality , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Area Under Curve , Blood Vessel Prosthesis Implantation/adverse effects , Chi-Square Distribution , Discriminant Analysis , Elective Surgical Procedures , Endovascular Procedures/adverse effects , England/epidemiology , Female , Hospital Mortality , Humans , Male , Medical Audit , Prospective Studies , ROC Curve , Reproducibility of Results , Risk Assessment , Risk Factors , Treatment Outcome
17.
Eur J Vasc Endovasc Surg ; 47(5): 487-92, 2014 May.
Article in English | MEDLINE | ID: mdl-24618331

ABSTRACT

OBJECTIVE: CT angiography (CTA) for endovascular aneurysm repair (EVAR) surveillance involves irradiation and nephrotoxic X-ray contrast agents. Three-dimensional contrast enhanced ultrasound (3D CEUS) is a novel imaging technique that may be more sensitive to blood flow detection than CTA or 2D CEUS. 3D CEUS utilises positional information from magnetic field emitters to assemble all ultrasound reflections into a high-definition image. We compared 3D CEUS with CTA for the detection of endoleak and aneurysm expansion following EVAR. METHODS: 3D CEUS (Curefab), 2D CEUS (Philips IU22), and CTA were compared in 30-paired images from 23 patients. Sensitivity, specificity, positive, and negative predictive value were calculated for 2D and 3D CEUS against CTA as the 'gold standard'. Pearson correlation was used to compare aneurysm sac diameter. Data were analysed using SPSS version 19.0. RESULTS: 30 paired 3D CEUS and CTA images were analysed from 23 patients. Endoleaks were detected in 17 images with CTA, 18 on 2D CEUS, and 18 on 3D CEUS. The sensitivity, specificity, positive, and negative predictive values of 3D CEUS to detect endoleak were 100%, 92%, 94%, and 100%, respectively. There was excellent correlation (r=0.935; p≤.0001) between CTA and 3D CEUS for AAA sac diameter. Only 3D CEUS detected the inflow and outflow arteries in all 18 scans with endoleak. 2D CEUS detected the inflow in 16 (88.8%) and CTA on 12 (66.6%) of the images. CONCLUSION: 3D CEUS may be more sensitive to endoleak following EVAR than either 2D CEUS or CTA.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Contrast Media , Endoleak/diagnostic imaging , Endovascular Procedures/adverse effects , Imaging, Three-Dimensional/methods , Ultrasonography, Doppler, Color/methods , Aged , Aortography , Endoleak/etiology , Endovascular Procedures/methods , Female , Follow-Up Studies , Humans , Male , Pilot Projects , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray Computed
18.
Br J Surg ; 100(5): 645-53, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23338659

ABSTRACT

BACKGROUND: Mortality results for elective abdominal aortic aneurysm (AAA) repair are published by the Vascular Society of Great Britain and Ireland. These mortality results are not currently risk-adjusted. The objective of this study was to develop a national risk prediction model for elective AAA repair. METHODS: Data for consecutive patients undergoing elective AAA repair from the National Vascular Database between April 2008 and March 2011 were analysed. Multiple logistic regression and backwards model selection were used for model development. The study outcome measure was in-hospital mortality. Model calibration and discrimination were assessed for all AAA repairs, and separately for open repair and endovascular aneurysm repair (EVAR) subgroups. RESULTS: There were 312 in-hospital deaths among 11,423 AAA repairs (2.7 (95 per cent confidence interval (c.i.) 2.4 to 3.0) per cent): 230 after 4940 open AAA repairs (4.7 (4.1 to 5.3) per cent) and 82 after 6483 EVARs (1.3 (1.0 to 1.6) per cent). Variables associated with in-hospital death included in the final model were: open repair, increasing age, female sex, serum creatinine level over 120 µmol/l, cardiac disease, abnormal electrocardiogram, previous aortic surgery or stent, abnormal white cell count, abnormal serum sodium level, AAA diameter and American Society of Anesthesiologists fitness grade. The area under the receiver operating characteristic (ROC) curve was 0.781 (95 per cent c.i. 0.756 to 0.806) with a bias-corrected value of 0.774. Model calibration was good (P = 0.963) based on the Hosmer-Lemeshow goodness-of-fit test, (bias-corrected) calibration curves, risk group assessment and recalibration regression. CONCLUSION: This multivariable model for elective AAA repair can be used to risk-adjust outcome analyses and provide patient-specific estimates of in-hospital mortality risk for open AAA repair or EVAR.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Elective Surgical Procedures/mortality , Vascular Surgical Procedures/mortality , Adult , Aged , Endovascular Procedures/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , ROC Curve , Risk Assessment/methods , United Kingdom/epidemiology
19.
Eur J Vasc Endovasc Surg ; 45(2): 128-34, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23273900

ABSTRACT

OBJECTIVES: Currently most abdominal aortic aneurysm screening programmes discharge patients with aortic diameter of less than 30 mm. However, sub-aneurysmal aortic dilatation (25 mm-29 mm) does not represent a normal aortic diameter. This observational study aimed to determine the outcomes of patients with screening detected sub aneurysmal aortic dilatation. DESIGN AND METHODS: Individual patient data was obtained from 8 screening programmes that had performed long term follow up of patients with sub aneurysmal aortic dilatation. Outcome measures recorded were the progression to true aneurysmal dilatation (aortic diameter 30 mm or greater), progression to size threshold for surgical intervention (55 mm) and aneurysm rupture. RESULTS: Aortic measurements for 1696 men and women (median age 66 years at initial scan) with sub-aneurysmal aortae were obtained, median period of follow up was 4.0 years (range 0.1-19.0 years). Following Kaplan Meier and life table analysis 67.7% of patients with 5 complete years of surveillance reached an aortic diameter of 30 mm or greater however 0.9% had an aortic diameter of 54 mm. A total of 26.2% of patients with 10 complete years of follow up had an AAA of greater that 54 mm. CONCLUSION: Patients with sub-aneurysmal aortic dilatation are likely to progress and develop an AAA, although few will rupture or require surgical intervention.


Subject(s)
Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/diagnosis , Mass Screening , Aged , Aorta, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/etiology , Aortic Rupture/pathology , Dilatation, Pathologic , Disease Progression , Europe , Female , Humans , Kaplan-Meier Estimate , Male , Mass Screening/methods , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Time Factors , Ultrasonography , Vascular Surgical Procedures
20.
Br J Surg ; 99(11): 1539-46, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23001820

ABSTRACT

BACKGROUND: Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity. The aim of this study was to assess whether preoperative CPET identifies patients at risk of early death following elective open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Prospective data were collected from a pilot study between September 2005 and February 2007, and from all patients who underwent CPET before elective AAA repair at two vascular centres between February 2007 and November 2011. Symptom-limited, maximal CPET was performed on each patient. Univariable and multivariable analyses were used to identify risk factors for 30- and 90-day mortality. RESULTS: Some 415 patients underwent CPET before elective AAA repair. Anaerobic threshold (AT), peak oxygen consumption (peak V.O(2) ) and ventilatory equivalents for carbon dioxide were associated with 30- and 90-day mortality on univariable analysis. On multivariable analysis, open repair (odds ratio (OR) 4·92, 95 per cent confidence interval 1·55 to 17·00; P = 0·008), AT below 10·2 ml per kg per min (OR 6·35, 1·84 to 29·80; P = 0·007), anaemia (OR 3·27, 1·04 to 10·50; P = 0·041) and inducible cardiac ischaemia (OR 6·16, 1·48 to 23·07; P = 0·008) were associated with 30-day mortality. Anaemia, inducible cardiac ischaemia and peak V.O(2) less than 15 ml per kg per min (OR 8·59, 2·33 to 55·75; P = 0·005) were associated with 90-day mortality on multivariable analysis. Patients with two or more subthreshold CPET values were at increased risk of both 30- and 90-day mortality. CONCLUSION: An AT below 10·2 ml per kg per min, peak V.O(2) less than 15 ml per kg per min and at least two subthreshold CPET values identify patients at increased risk of early death following AAA repair.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Exercise Test/methods , Postoperative Complications/mortality , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/mortality , Exercise Test/mortality , Female , Humans , Male , Middle Aged , Oxygen Consumption/physiology , Pilot Projects , Preoperative Care/methods , Preoperative Care/mortality , Prospective Studies , Risk Assessment , Risk Factors , Young Adult
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