ABSTRACT
BACKGROUND: There is limited evidence that the diabetes in-person consult in hospitalized patients can be replaced by a virtual consult. During COVID-19 pandemic, the diabetes in-person consult service at the University of Miami and Miami Veterans Affairs Healthcare System transitioned to a virtual model. The aim of this study was to assess the impact of telemedicine on glycemic control after this transition. METHODS: We retrospectively analyzed glucose metrics from in-person consults (In-person) during January 16 to March 14, 2020 and virtual consults during March 15 to May 14, 2020. Data from virtual consults were analyzed by separating patients infected with COVID-19, who were seen only virtually (Virtual-COVID-19-Pos), and patients who were not infected (Virtual-COVID-19-Neg), or by combining the two groups (Virtual-All). RESULTS: Patient-day-weighted blood glucose was not significantly different between In-person, Virtual-All, and Virtual-COVID-19-Neg, but Virtual-COVID-19-Pos had significantly higher mean ± SD blood glucose (mg/dL) compared with others (206.7 ± 49.6 In-person, 214.6 ± 56.2 Virtual-All, 206.5 ± 57.2 Virtual-COVID-19-Neg, 229.7 ± 51.6 Virtual-COVID-19-Pos; P = .015). A significantly less percentage of patients in this group also achieved a mean ± SD glucose target of 140 to 180 mg/dL (23.8 ± 22.5 In-person, 21.5 ± 20.5 Virtual-All, 25.3 ± 20.8 Virtual-COVID-19-Neg, and 14.4±18.1 Virtual-COVID-19-Pos, P = .024), but there was no significant difference between In-person, Virtual-All, and Virtual-COVID-19-Neg. The occurrence of hypoglycemia was not significantly different among groups. CONCLUSIONS: In-person and virtual consults delivered by a diabetes team at an academic institution were not associated with significant differences in glycemic control. These real-world data suggest that telemedicine could be used for in-patient diabetes management, although additional studies are needed to better assess clinical outcomes and safety.
ABSTRACT
Translational research is a data-driven process that involves transforming scientific laboratory- and clinic-based discoveries into products and activities with real-world impact to improve individual and population health. Successful execution of translational research requires collaboration between clinical and translational science researchers, who have expertise in a wide variety of domains across the field of medicine, and qualitative and quantitative scientists, who have specialized methodologic expertise across diverse methodologic domains. While many institutions are working to build networks of these specialists, a formalized process is needed to help researchers navigate the network to find the best match and to track the navigation process to evaluate an institution's unmet collaborative needs. In 2018, a novel analytic resource navigation process was developed at Duke University to connect potential collaborators, leverage resources, and foster a community of researchers and scientists. This analytic resource navigation process can be readily adopted by other academic medical centers. The process relies on navigators with broad qualitative and quantitative methodologic knowledge, strong communication and leadership skills, and extensive collaborative experience. The essential elements of the analytic resource navigation process are as follows: (1) strong institutional knowledge of methodologic expertise and access to analytic resources, (2) deep understanding of research needs and methodologic expertise, (3) education of researchers on the role of qualitative and quantitative scientists in the research project, and (4) ongoing evaluation of the analytic resource navigation process to inform improvements. Navigators help researchers determine the type of expertise needed, search the institution to find potential collaborators with that expertise, and document the process to evaluate unmet needs. Although the navigation process can create a basis for an effective solution, some challenges remain, such as having resources to train navigators, comprehensively identifying all potential collaborators, and keeping updated information about resources as methodologists join and leave the institution.
Subject(s)
Medicine , Physicians , Humans , Academic Medical Centers , Leadership , Translational Research, BiomedicalABSTRACT
Receiver operating characteristic curves are widely used in medical research to illustrate biomarker performance in binary classification, particularly with respect to disease or health status. Study designs that include related subjects, such as siblings, usually have common environmental or genetic factors giving rise to correlated biomarker data. The design could be used to improve detection of biomarkers informative of increased risk, allowing initiation of treatment to stop or slow disease progression. Available methods for receiver operating characteristic construction do not take advantage of correlation inherent in this design to improve biomarker performance. This paper will briefly review some developed methods for receiver operating characteristic curve estimation in settings with correlated data from case-control designs and will discuss the limitations of current methods for analyzing correlated familial paired data. An alternative approach using conditional receiver operating characteristic curves will be demonstrated. The proposed approach will use information about correlation among biomarker values, producing conditional receiver operating characteristic curves that evaluate the ability of a biomarker to discriminate between affected and unaffected subjects in a familial paired design.
Subject(s)
Diagnostic Tests, Routine , Models, Statistical , Area Under Curve , Biomarkers , Case-Control Studies , Humans , ROC CurveABSTRACT
BACKGROUND AND OBJECTIVES: Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested the hypothesis that high plasma FGF23 is an independent risk factor for CKD progression in 419 children, aged 1-16 years, enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. We measured plasma FGF23 concentrations at baseline and determined GFR annually using plasma disappearance of iohexol or the CKiD study estimating equation. We analyzed the association of baseline FGF23 with risk of progression to the composite end point, defined as start of dialysis or kidney transplantation or 50% decline from baseline GFR, adjusted for demographics, baseline GFR, proteinuria, other CKD-specific factors, and other mineral metabolites. RESULTS: At enrollment, median age was 11 years [interquartile range (IQR), 8-15], GFR was 44 ml/min per 1.73 m2 (IQR, 33-57), and FGF23 was 132 RU/ml (IQR, 88-200). During a median follow-up of 5.5 years (IQR, 3.5-6.6), 32.5% of children reached the progression end point. Higher FGF23 concentrations were independently associated with higher risk of the composite outcome (fully adjusted hazard ratio, 2.52 in the highest versus lowest FGF23 tertile; 95% confidence interval, 1.44 to 4.39, P=0.002; fully adjusted hazard ratio, 1.33 per doubling of FGF23; 95% confidence interval, 1.13 to 1.56, P=0.001). The time to progression was 40% shorter for participants in the highest compared with the lowest FGF23 tertile. In contrast, serum phosphorus, vitamin D metabolites, and parathyroid hormone did not consistently associate with progression in adjusted analyses. CONCLUSIONS: High plasma FGF23 is an independent risk factor for CKD progression in children.
Subject(s)
Disease Progression , Fibroblast Growth Factors/blood , Renal Insufficiency, Chronic/blood , Adolescent , Child , Female , Fibroblast Growth Factor-23 , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kidney Transplantation , Male , Parathyroid Hormone/blood , Phosphorus/blood , Prospective Studies , Renal Dialysis , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/therapy , Risk Assessment , Risk Factors , Vitamin D/analogs & derivatives , Vitamin D/bloodABSTRACT
BACKGROUND: Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. METHODS: We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. RESULTS: The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. CONCLUSION: This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs.
Subject(s)
Filgrastim/therapeutic use , Graft Survival/drug effects , Hematologic Agents/therapeutic use , Hypoglycemic Agents/therapeutic use , Islets of Langerhans Transplantation/methods , Islets of Langerhans/drug effects , Peptides/therapeutic use , Venoms/therapeutic use , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Daclizumab , Exenatide , Humans , Hyperglycemia/drug therapy , Hyperglycemia/etiology , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/therapeutic use , Islets of Langerhans/physiology , Islets of Langerhans Transplantation/adverse effects , Middle Aged , Neutropenia/drug therapy , Neutropenia/etiology , Retrospective Studies , Transplantation, HomologousABSTRACT
Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas-kidney (SPK) transplants for over 25 years and find that 6-8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.
Subject(s)
Autoimmunity , Diabetes Mellitus, Type 1/immunology , Pancreas Transplantation , Autoantibodies/blood , Autoantibodies/immunology , Diabetes Mellitus, Type 1/surgery , Humans , Pancreas/immunology , Pancreas/surgery , RecurrenceABSTRACT
Criteria for evaluating faculty are traditionally based on a triad of scholarship, teaching, and service. Research scholarship is often measured by first or senior authorship on peer-reviewed scientific publications and being principal investigator on extramural grants. Yet scientific innovation increasingly requires collective rather than individual creativity, which traditional measures of achievement were not designed to capture and, thus, devalue. The authors propose a simple, flexible framework for evaluating team scientists that includes both quantitative and qualitative assessments. An approach for documenting contributions of team scientists in team-based scholarship, nontraditional education, and specialized service activities is also outlined. Although biostatisticians are used for illustration, the approach is generalizable to team scientists in other disciplines.The authors offer three key recommendations to members of institutional promotion committees, department chairs, and others evaluating team scientists. First, contributions to team-based scholarship and specialized contributions to education and service need to be assessed and given appropriate and substantial weight. Second, evaluations must be founded on well-articulated criteria for assessing the stature and accomplishments of team scientists. Finally, mechanisms for collecting evaluative data must be developed and implemented at the institutional level. Without these three essentials, contributions of team scientists will continue to be undervalued in the academic environment.
Subject(s)
Academic Medical Centers , Cooperative Behavior , Employee Performance Appraisal , Faculty, Medical/standards , Research , Authorship , Faculty/standards , Humans , TeachingABSTRACT
Objectives. Although people with HIV experience significant oral health problems, many consistently identify oral health as an unmet health care need. We conducted a randomized controlled trial to evaluate the impact of a dental case management intervention on dental care use. Methods. We evaluated the intervention according to self-reported dental care use at 6-, 12-, and 18-month follow-ups. Multivariable logistic models with generalized estimating equations were used to assess the effects of the intervention over time. Results. The odds of having a dental care visit were about twice as high in the intervention group as in the standard care group at 6 months (adjusted odds ratio [OR] = 2.52; 95% confidence interval [CI] = 1.58, 4.08) and 12 months (adjusted OR = 1.98; 95% CI = 1.17, 3.35), but the odds were comparable in the 2 groups by 18 months (adjusted OR = 1.07; 95% CI = 0.62, 1.86). Factors significantly associated with having a dental care visit included frequent physician visits and dental care referrals. Conclusions. We demonstrated that a dental case management intervention targeting people with HIV was efficacious but not sustainable over time. Barriers not addressed in the intervention must be considered to sustain its use over time.
ABSTRACT
OBJECTIVES: Using a nationally representative survey, we determined dentists' willingness to provide oral rapid HIV screening in the oral health care setting. METHODS: From November 2010 through November 2011, a nationally representative survey of general dentists (sampling frame obtained from American Dental Association Survey Center) examined barriers and facilitators to offering oral HIV rapid testing (n = 1802; 70.7% response). Multiple logistic regression analysis examined dentists' willingness to conduct this screening and perceived compatibility with their professional role. RESULTS: Agreement with the importance of annual testing for high-risk persons and familiarity with the Centers for Disease Control and Prevention's recommendations regarding routine HIV testing were positively associated with willingness to conduct such screening. Respondents' agreement with patients' acceptance of HIV testing and colleagues' improved perception of them were also positively associated with willingness. CONCLUSIONS: Oral HIV rapid testing is potentially well suited to the dental setting. Although our analysis identified many predictors of dentists' willingness to offer screening, there are many barriers, including dentists' perceptions of patients' acceptance, that must be addressed before such screening is likely to be widely implemented.
Subject(s)
Attitude of Health Personnel , Dentists/psychology , HIV Infections/diagnosis , Mass Screening/psychology , Adult , Age Factors , Aged , Centers for Disease Control and Prevention, U.S. , Female , HIV Infections/ethnology , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Perception , Referral and Consultation , Sex Factors , Socioeconomic Factors , United StatesABSTRACT
We evaluated whether 1,5-anhydroglucitol (1,5-AG) (GlycoMark(®)), a test for measuring postprandial glucose and glucose variability, could be a tool for assessing short-term glycemic control in islet cell transplant (ICT) subjects. Data of 21 subjects, with type 1 DM and allogenic islet transplantation, who had concomitant fructosamine, HbA1c, 1,5-AG (n = 85 samples), and capillary glucose self-monitoring measurements (n = 2,979) were analyzed retrospectively at different time points after ICT. A significant negative association was observed between 1,5-AG and HbA1c (p = 0.02), but not with fructosamine. When HbA1c was divided in quartiles as <5.6, 5.6-5.9, 5.9-6.2, and >6.2, a decrease of an estimated 0.70 ± 0.30 µg/ml in 1,5-AG was associated with each quartile of increase in HbA1c (p < 0.0001). There was a significant decline of 1.64 ± 0.3mg/dl in postprandial glucose values for each 1 unit increase in 1,5-AG (p < 0.0001). For those with HbA1c ≥ 6.0% when 1,5-AG was ≥8.15 µg/ml, the mean estimated glucose level was 103.71 ± 3.66 mg/dl, whereas it was 132.12 ± 3.71 mg/dl when 1,5-AG was <8.15 µg/ml. The glucose variability (Glumax - Glumin) in subjects with 1,5-AG <8.15 µg/ml was 46.23 mg/dl greater than the subjects with 1,5-AG ≥8.15 µg/ml (HbA1c ≥ 6.0%). There was no significant association between GlycoMark and glucose variability where HbA1c < 6%. 1,5-AG significantly associated with postprandial glucose levels and glucose variability in ICT recipients with near-normal HbA1c (6.0-6.5%) levels. These findings suggest that 1,5-AG can be used to differentiate those ICT subjects with higher glucose variability despite having near-normal HbA1c. However, prospective studies are needed to evaluate the association between GlycoMark levels and the parameters of graft dysfunction/failure.
Subject(s)
Blood Glucose/metabolism , Deoxyglucose/blood , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Glycated Hemoglobin/metabolism , Islets of Langerhans Transplantation/methods , Female , Humans , Male , Middle Aged , Postprandial Period , Retrospective Studies , Transplant RecipientsABSTRACT
BACKGROUND AND OBJECTIVES: In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR. RESULTS: Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2). CONCLUSION: In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.
Subject(s)
Fibroblast Growth Factors/blood , Renal Insufficiency, Chronic/blood , Adolescent , Age Factors , Biomarkers/blood , Calcium/metabolism , Canada , Child , Child, Preschool , Creatinine/blood , Cross-Sectional Studies , Cystatin C/blood , Early Diagnosis , Fibroblast Growth Factor-23 , Glomerular Filtration Rate , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/etiology , Infant , Kidney/physiopathology , Parathyroid Hormone/blood , Phosphorus/blood , Predictive Value of Tests , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , United States , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/etiologyABSTRACT
OBJECTIVES/HYPOTHESIS: To examine the significance of indeterminate fine needle aspiration biopsy in the diagnosis of parotid gland malignancy. STUDY DESIGN: Retrospective case series, academic tertiary referral center. METHODS: A total of 559 parotidectomies performed between the years of 2005 and 2010 were reviewed, with 56.7% (N = 317) meeting investigation eligibility criteria: primary parotid tumor, availability of fine-needle aspiration biopsy, intraoperative frozen section, and final pathologic diagnosis. One-hundred fifteen (n = 115, 36.3%) of the 317 parotid biopsies were interpreted as indeterminate. Clinical history, physical examination, operative findings, and histopathologic characteristics were analyzed. Multiple logistic regression, with deviation from means coding, was used to estimate the odds of malignancy in the indeterminate group and provide a comparison with reference to the average odds of malignancy over the overall sample. RESULTS: Overall final pathologic distribution of parotid masses (N = 317) was 82.3% benign and 17.7% malignant. Overall final pathologic distribution of parotid masses in the indeterminate group (n = 115) was 31.3% malignant and 68.7% benign. In comparison, the overall group (N = 317) had a decreased comparative percentage of malignant specimens at 17.7%. Interestingly, in the instance of an indeterminate biopsy, the odds of having a malignancy was estimated to increase by 1.98-fold compared to overall mean odds of malignancy in the sample. Other statistically significant clinical predictors of parotid malignancy included history of prior malignancy, current tobacco user, locally invasive characteristics intraoperatively, and facial nerve involvement intraoperatively. CONCLUSIONS: In the context of an indeterminate fine-needle aspiration biopsy, an elevated index of suspicion for parotid malignancy may be warranted.
Subject(s)
Biopsy, Fine-Needle , Parotid Gland/pathology , Parotid Neoplasms/pathology , Parotid Neoplasms/surgery , Academic Medical Centers , Adult , Aged , Cohort Studies , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Immunohistochemistry , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Odds Ratio , Parotid Diseases/pathology , Parotid Diseases/surgery , Parotid Gland/surgery , Parotid Neoplasms/diagnosis , Parotid Neoplasms/mortality , Preoperative Care/methods , Retrospective Studies , Risk Assessment , Survival Analysis , Tertiary Care Centers , Treatment OutcomeABSTRACT
As with other animal species, comprehensive reference intervals (RI) for psittaciform species are rare and plagued by common issues, including sparse information regarding methods used to analyze specimens, low sample sizes, and improper statistical analyses. The purpose of this study was to examine the use of an indirect sampling method of RI generation from several years of data collected from specimens of multiple psittaciform species submitted to a veterinary diagnostic laboratory. These data were unselected for health status. A previously published method for indirect RI generation was applied to data collected for routine hematologic and biochemical analyses. Seven species groups were examined, and sample size ranged from 346 to 2358. Results showed that RI varied by species and appeared to represent a broader range than expected compared with other RI and traditional clinical expectations for core health assessments, such as total white blood cell count and white blood cell differential results. Some biochemical results reflected more narrow ranges, and a few were consistent with other published ranges. The intervals were likely influenced by changes related to stress and underlying disease. The results of the current study reflect the imprecision of this method related to data obtained from the population served by this laboratory. Overall, this method is not suitable for the production of comprehensive RI, although it may provide rough estimates for some limited analyses until traditional RI can be generated.
Subject(s)
Blood Cell Count/veterinary , Blood Chemical Analysis/veterinary , Blood Physiological Phenomena , Psittaciformes/blood , Animals , Reference Values , Species SpecificityABSTRACT
OBJECTIVE: To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS: A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999-2002), mid (2003-2006), or recent (2007-2010) transplant era based on annual follow-up to 5 years. RESULTS: Insulin independence at 3 years after transplant improved from 27% in the early era (1999-2002, n = 214) to 37% in the mid (2003-2006, n = 255) and to 44% in the most recent era (2007-2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA(1c) and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007-2010 vs. 60-65% in 1999-2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001). CONCLUSIONS: The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007-2010 compared with those in 1999-2006, with fewer islet infusions and adverse events per recipient.
Subject(s)
Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation , Adolescent , Adult , Aged , Blood Glucose/metabolism , C-Peptide/metabolism , Glycated Hemoglobin/metabolism , Humans , Islets of Langerhans Transplantation/adverse effects , Middle Aged , Registries , Treatment OutcomeABSTRACT
CONTEXT: Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease. OBJECTIVE: To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor. DESIGN, SETTING, AND PATIENTS: One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed. INTERVENTION: Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs. MAIN OUTCOME MEASURES: The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events. RESULTS: Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m(2) (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02) CONCLUSION: Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00658073.
Subject(s)
Immunosuppression Therapy/methods , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods , Adolescent , Adult , Antibodies/therapeutic use , Antibody Formation , Calcineurin Inhibitors , Female , Graft Rejection/prevention & control , Humans , Kidney/physiology , Kidney Transplantation/immunology , Living Donors , Male , Middle Aged , Opportunistic Infections , Receptors, Interleukin-2/antagonists & inhibitors , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The 2007 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on Perioperative Cardiac Evaluation and Care for Noncardiac Surgery is the accepted standard for perioperative cardiac evaluation. Anesthesiology training programs are required to teach these algorithms. We estimated the percentage of residents nationwide who correctly applied suggested testing algorithms from the ACC/AHA guidelines when they evaluated simulated patients in common clinical scenarios. METHODS: Anesthesiology resident volunteers at 24 training programs were presented with 6 scenarios characterized by surgical procedure, patient's risk factors, and patient's functional capacity. Scenarios and 5 possible recommendations per scenario were both presented in randomized orders. Senior anesthesiologists at 24 different United States training programs along with the first author of the 2007 ACC/AHA guidelines validated the appropriate recommendation to this web-based survey before distribution. RESULTS: The 548 resident participants, representing 12% of anesthesiology trainees in the United States, included 48 PGY-1s (preliminary year before anesthesia training), 166 Clinical Anesthesia Year 1 (CA-1) residents, 161 CA-2s, and 173 CA-3s. For patients with an active cardiac condition, the upper 95% confidence bound for the percent of residents who recommended evaluations consistent with the guidelines was 78%. However, for the remaining 5 scenarios, the upper 95% confidence bound for the percent of residents with an appropriate recommendation was 46%. CONCLUSIONS: The results show that fewer than half of anesthesiology residents nationwide correctly demonstrate the approach considered the standard of care for preoperative cardiac evaluation. Further study is necessary to elucidate the correct intervention(s), such as use of decision support tools, increased clarity of guidelines for routine use, adjustment in educational programs, and/or greater familiarity of responsible faculty with the material.
Subject(s)
American Heart Association , Anesthesiology/standards , Cardiology/standards , Clinical Competence/standards , Internship and Residency/standards , Patient Simulation , Perioperative Care/standards , Anesthesiology/methods , Cardiology/methods , Humans , Internship and Residency/methods , Patient Care/methods , Patient Care/standards , Perioperative Care/methods , Societies, Medical/standards , United StatesABSTRACT
There is a need for biomarkers to monitor the development and progression of type 1 DM. We analyzed mRNA expression levels for granzyme B, perforin, fas ligand, TNF-α, IFN-γ, Foxp3, IL-10, TGF-ß, IL-4, IL-6, IL-17, Activation-induced cytidine deaminase (AID) and Immunoglobulin G gamma chain (IgG
Subject(s)
Cytokines/genetics , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Adolescent , Adult , Biomarkers/blood , Cytokines/biosynthesis , Cytokines/immunology , Diabetes Mellitus, Type 1/blood , Female , Gene Expression Profiling/methods , Humans , Linear Models , Male , Multivariate Analysis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Young AdultABSTRACT
Pancreatic islet allotransplantation is an option for patients with unstable type 1 diabetes mellitus (T1DM). Major improvements in islet isolation techniques and the implementation of steroid-free immunosuppressive regimens can maintain insulin independence in the majority of T1DM for at least 1 year after transplantation. Recent studies have emphasized the impact of sirolimus on female reproductive tract. In this communication we report on the alterations of the female reproductive tract in 18 chronically immunosuppressed patients with T1DM following allogenic islet transplantation. Previous research has shown development of ovarian cysts in islet transplant patients receiving sirolimus. We extensively reevaluated this and other possible side effects on the female reproductive system. These side effects have been underestimated, although they are significant, requiring surgical or intensive medical treatment. Pre- and posttransplant gynecological evaluation should be performed to address the development of complications secondary to sirolimus in order to intervene sooner with alternative therapies.
Subject(s)
Genitalia, Female/drug effects , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/adverse effects , Islets of Langerhans Transplantation/methods , Sirolimus/adverse effects , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/surgery , Female , Humans , Immunosuppressive Agents/therapeutic use , Middle Aged , Sirolimus/therapeutic useABSTRACT
We investigated the use of dental care services among a population of low-income persons living with HIV/AIDS who had not seen a dental care provider during the 12 months prior to study enrollment. A total of 593 participants were recruited from five HIV primary care clinics in two South Florida counties and interviewed regarding past utilization of dental care services, HIV primary care service utilization, and barriers to care. Multivariate logistic regression analysis was used to determine correlates of oral care utilization within the preceding two years. One-third of respondents reported seeing a dentist in the preceding two years. The odds of having seen a dentist were greater for respondents with stable housing, more than a high school education, and who had received help in getting dental care; black respondents (compared to Hispanics and non-Hispanic whites) were less likely to have seen a dentist in the preceding two years. Despite the availability of dental services for low-income HIV-positive persons, utilization of dental care remains low. This study reinforces the need to provide assistance to HIV-positive persons in obtaining dental care. In particular, it indicates that such assistance should be targeted toward Black Americans, persons with low income and unstable housing situations, and those with limited help to navigate the health care system.