US–National Institutes of Health‐funded research for cutaneous wounds in 2012

Chronic cutaneous wounds are a major burden on patients, healthcare providers, and the US healthcare system. This study, carried out in part by the Wound Healing Society's Government Regulatory Committee, aimed to evaluate the current state of National Institutes of Health funding of cutaneous wound healing–related research projects. National Institutes of Health Research Portfolio Online Reporting Tools Expenditures & Results system was used to identify wound healing projects funded by the National Institutes of Health in the 2012 fiscal year. Research projects focusing on cutaneous wound prevention/education, mechanisms, complications, treatment, or imaging/monitoring were included in the analysis. Ninety‐one projects were identified, totaling a collective funding of $29,798,991 and median funding of $308,941. Thirteen institutes/centers from the National Institutes of Health were responsible for awarding funds; three of which (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%). New applications and pre‐existing applications accounted for 39.6 and 55.0% of the awarded grants, respectively. Grants awarded to investigators affiliated with universities accounted for 68.1% of grants and 25.3% were to investigators in the private sector. This analysis of current National Institutes of Health funding may facilitate more transparency of National Institutes of Health‐allocated research funds and serve as an impetus to procure additional support for the field of wound healing.     

Enhancing clinical trial design of interventions for posttraumatic stress disorder

The 2008 Institute of Medicine review of interventions research for posttraumatic stress disorder (PTSD) concluded that new, well‐designed studies are needed to evaluate the efficacy of treatments for PTSD. The Department of Veterans Affairs (VA), the Department of Defense, and the National Institute of Mental Health convened a meeting on research methodology and the VA issued recommendations for design and analysis of randomized controlled clinical trials (RCTs) for PTSD. The rationale that formed the basis for several of the components of the recommendations is discussed here. Fundamental goals of RCT design are described. Strategies in design and analysis that contribute to the goals of an RCT and thereby enhance the likelihood of signal detection are considered.     

Medicare‐VHA dual use is associated with poorer chronic wound healing

Veterans who use Veterans Health Affairs (VHA) have the option of enrolling in and obtaining care from other non‐VA sources. Dual system use may improve care by increasing options or it may result in poorer outcomes because of fragmented care. Our objective was to assess whether dual system use of VHA and Medicare for wound care was associated with chronic wound healing. We conducted a retrospective cohort study of 227 Medicare‐enrolled VHA users in the Pacific Northwest who had an incident, chronic lower limb wound between October 1, 2006 and September 30, 2007 identified through VHA chart review. All wounds were followed until resolution or for up to one year. Dual system wound care was identified through Medicare claims during follow‐up. We used a proportional hazards model to compare wound healing among VHA‐exclusive and dual wound care users, using a time‐varying measure of dual use and treating amputation and death as competing risks. About 18.1% of subjects were classified as dual wound care users during follow‐up. After adjustment using propensity scores, dual use was associated with a significantly lower hazard of wound healing compared to VHA‐exclusive use (HR = 0.63, 95%CI: 0.39–0.99, p = 0.047). Hazards for the competing risks, amputation (HR = 4.23, 95% CI: 1.61–11.15, p = 0.003) and death (HR = 3.08, 95%CI: 1.11–8.56, p = 0.031), were significantly higher for dual users compared to VHA‐exclusive users. Results were similar in inverse probability of treatment weighted analyses and in sensitivity analyses that excluded veterans enrolled in a Medicare managed care plan and that used a revised wound resolution date based on Medicare claims data, but were not always statistically significant. Overall, dual wound care use was associated with substantially poorer wound healing compared to VHA‐exclusive wound care use. VHA may need to design programs or policies that support and improve care coordination for veterans needing chronic wound care.     

Surgical quality programs in the Veterans Health Administration

This review describes the development, implementation, and current status of programs that promote and maintain surgical quality performance within the Department of Veterans Affairs, Veterans Health Administration (VHA). It also considers evolving initiatives to improve surgical outcomes and enhance patient safety. The VHA is a nationwide health care system operated and funded by the federal government. It consists of 154 federal hospitals and 875 clinics staffed by 16,000 nurses, 33,000 other health care professionals, 15,000 doctors, and 25,000 university-affiliated faculty physicians. The VHA trains 90,000 health care professionals, and additionally its activities are supported by 140,000 dedicated volunteers. More than 1000 surgeons in all specialties serve in its facilities. Since these programs began more than 19 years ago, there has been a steady decrease in both risk-adjusted and actual mortality rates tracked annually.     

Agenda for women's health research. Improving women's musculoskeletal health

Increased attention and resources focused on women's health during the past decade have resulted in new offices, policies, and programs of the Federal government. The Office of Research on Women's Health, established by the National Institutes of Health in 1990, is a focal point for all National Institutes of Health-supported efforts to improve women's health through biomedical and behavioral research. The Office of Research on Women's Health ensures women's appropriate inclusion in research studies supported by the National Institutes of Health. Through the development of a comprehensive agenda for research on women's health, the Office of Research on Women's Health encourages the consideration of gender issues and gender differences in health and disease in research sponsored by the National Institutes of Health. The importance of research to study and improve women's musculoskeletal health has become increasingly recognized. Clinicians, researchers, and representatives of professional and advocacy organizations concerned with women's musculoskeletal health participated in the development of the initial research agenda on women's health in 1991 and participated in the meetings to update and revise the agenda in 1996 and 1997. As a result of meetings convened to review and revise the agenda on women's health for the twenty-first century, many recommendations for additional research on women's musculoskeletal health have been developed and now are being implemented across the National Institutes of Health.     

Experimental approaches to chronic wounds

The pathogenesis of most chronic wounds is unknown. In this report, we summarize several areas of investigation which appear ready for further progress and which were discussed at a recent National Institutes of Health workshop on this subject. Of note were presentations of research on the role of fibrosis in wound healing, interaction of cytokines, hypoxia, extracellular matrix formation, keratinocyte migration, and involvement of proteases and neuropeptides in chronic wounds.     

The VA Transplant Program: A rebuttal to criticism and a look to the future

The Department of Veterans Affairs (VA) Transplant Program was established decades ago, is well resourced, and provides timely and high quality solid organ transplant care and services to a Nation of Veterans. In the past few years, the VA Transplant Program has received criticism that can be characterized as follows: the location of VA Transplant Centers (VATCs) requires Veterans to travel considerable distances for transplant care and services; the National Surgery Office (NSO) that provides oversight limits the number of active VATCs; Veterans Health Administration (VHA) policy limits referral of Veterans to non‐VA transplant centers (community care); and the VA Transplant Program does not provide living donor transplant procedures. The MISSION Act of 2018 (Public Law 115‐182) was enacted in part to address these themes by promoting community care and living donation. This article provides perspective regarding the VA Transplant Program and rebuttal to stated criticism: Travel to a transplant center is not isolated to the VA; the NSO does not limit VATC activation; current VHA policy authorizes community care; and the VA Transplant Program currently performs living donor procedures. The MISSION Act, as intended, has the potential to decrease referrals to the VA Transplant Program by 30%.     

Prevalence of a Positive Screen for PTSD Among OEF/OIF and OEF/OIF‐Era Veterans in a Large Population‐Based Cohort

Multiple studies have reported the prevalence of posttraumatic stress disorder (PTSD) in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans; however, these studies have been limited to populations who use the Department of Veterans Affairs (VA) for health care, specialty clinic populations, or veterans who deployed. The 3 aims of this study were to report weighted prevalence estimates of a positive screen for PTSD among OEF/OIF and nondeployed veterans, demographic subgroups, and VA health care system users and nonusers. The study analyzed data from the National Health Study for a New Generation of U.S. Veterans, a large population‐based cohort of OEF/OIF and OEF/OIF‐era veterans. The overall weighted prevalence of a positive screen for PTSD in the study population was 13.5%: 15.8% among OEF/OIF veterans and 10.9% in nondeployed veterans. Among OEF/OIF veterans, there was increased risk of a positive screen for PTSD among VA health care users (OR = 2.71), African Americans (OR = 1.61), those who served in the Army (OR = 2.67), and those on active duty (OR = 1.69). The same trend with decreased magnitude was observed in nondeployed veterans. PTSD is a significant public health problem in OEF/OIF‐era veterans, and should not be considered an outcome solely related to deployment.     

High‐dose folic acid and its effect on early stage diabetic foot ulcer wound healing

High‐dose folic acid (HDFA; vitamin B9)—5 mg, given daily, has not been evaluated as a treatment to improve early stage‐diabetic foot ulcer (ES‐DFU) wound healing. However, HDFA has been demonstrated to correct: (a) endothelial dysfunction and decreased nitric oxide (NO) bioavailability, associated with type‐2 diabetes mellitus (T2DM); and (b) hyperhomocysteinemia (HHcy) that may promote impaired DFU‐wound healing. Measures of wound area (cm²) reduction (wound closure; WC), over a 4‐week period (4 W‐WC), greater than 50% of the wound area, have been reported as a robust indicator of the potential for DFU‐wound healing. By using this model, we examined the effectiveness of a wound treatment in promoting progressive healing and complete wound closure for the chronic, nonhealing DFU‐wound. To investigate this possible relationship between HDFA and ES‐DFU wound healing, a retrospective cohort study of medical records, between November 2018 and April 2019, was performed for Veterans with T2DM and ES‐DFUs following treatment with HDFA. During the study period 29 (n = 29) Veterans with ES‐DFU wounds who received HDFA treatment were identified. Medical record reviews of this retrospective cohort of ES‐DFU Veterans receiving HDFA report 90% (26/29) experiencing complete DFU‐wound closure during the study period. Of the 29 Veterans with ES‐DFUs receiving HDFA, the medical records of nine (30%), with healed wounds, provided documentation suitable for 4 W‐WC, pre‐ and post‐HDFA treatment study comparisons. This study documents significant (P < .05) improvements comparing 4 W‐WC values for standard treatment for Veterans with poorly progressing, worsening or stagnating ES‐DFU‐wounds to those for the same subjects following HDFA treatment. These observations suggest that chronic ES‐DFUs treated with HDFA may experience significantly improved wound closure and complete healing (re‐epithelialization) when compared with standard treatments without HDFA. With validation from RCTs, HDFA may be established as an effective treatment to promote wound healing and closure for nonhealing ES‐DFUs.     

The pediatric surgeon's road to research independence: utility of mentor-based National Institutes of Health grants

Background

The current research environment for academic surgeons demands that extramural funding be obtained. Financial support from the National Institutes of Health (NIH) is historically the gold standard for funding in the biomedical research community, with the R01 funding mechanism viewed as indicator of research independence. The NIH also supports a mentor-based career development mechanism (K-series awards) in order to support early-stage investigators. The goal of this study was to investigate the grants successfully awarded to pediatric surgeon-scientists and then determine the success of the K-series award recipients at achieving research independence.

Methods

In July 2012, all current members of the American Pediatric Surgery Association (APSA) were queried in the NIH database from 1988–2012 through the NIH Research Portfolio Online Reporting Tools. The following factors were analyzed: type of grant, institution, amount of funding, and funding institute or center.

Results

Among current APSA members, there have been 83 independent investigators receiving grants, representing 13% of the current APSA membership, with 171 independent grants funded through various mechanisms. Six percent currently have active NIH funding, with $7.2 million distributed in 2012. There have been 28 K-series grants awarded. Of the recipients of expired K08 awards, 39% recipients were subsequently awarded an R01 grant. A total of 63% of these K-awarded investigators transitioned to an independent NIH award mechanism.

Conclusions

Pediatric surgeon-scientists successfully compete for NIH funding. Our data suggest that although the K-series funding mechanism is not the only path to research independence, over half of the pediatric surgeons who receive a K-award are successful in the transition to independent investigator.     

Cost‐effectiveness of becaplermin gel on wound healing of diabetic foot ulcers

We sought to determine the long‐term cost effectiveness (payer's perspective) of becaplermin gel plus good wound care (BGWC) vs. good wound care (GWC) alone in terms of wound healing and risk of amputation in patients with diabetic foot ulcers (DFUs). Outcomes data were derived from a propensity score‐matched cohort from the Curative Health Services database between 1998 and 2004, which was followed for 20 weeks. A four‐state Markov model was used to predict costs and outcomes of wound healing and risk of amputation for BGWC vs. GWC alone over 1 year in patients with DFU. The primary outcome was closed‐wound weeks. Transition probabilities for healing and amputation were derived from the aforementioned propensity score‐matched cohorts. Ulcer recurrence was estimated from the medical literature. Utilization for becaplermin was calculated using the dosing algorithm in the product labeling. Of 24,898 eligible patients, 9.6% received BGWC. Based on the model, patients treated with BGWC had substantially more closed‐wound weeks compared with GWC (16.1 vs. 12.5 weeks, respectively). More patients receiving BGWC had healed wounds at 1 year compared with those receiving GWC (48.1% vs. 38.3%). Risk of amputation was lower in the BGWC cohort (6.8% vs. 9.8%). Expected annual direct costs for DFU were $21,920 for BGWC and $24,640 for GWC. BGWC was economically dominant over GWC, providing better outcomes at a lower cost in patients with DFU. Compared with GWC alone, BGWC is more effective in healing wounds and lowering amputation risk, thereby decreasing long‐term costs for DFU.     

Research at US colleges of osteopathic medicine: a decade of growth

Although research is a critical component of academic medicine, it has not been a significant component of osteopathic medicine. For years, leaders in the osteopathic medical profession have called for increased research in osteopathic medical schools. The need for cost-effective clinical practice leading to improved clinical outcomes creates a necessity for conducting well-designed clinical outcomes research related to osteopathic practice. The authors assess the growth in research at osteopathic academic medical centers from 1989-1999. The amounts of extramural funding at each school, sources of funding, types of research funded, departments funded, and investigators' degree types are also assessed. During the 10 years analyzed, total research funding increased 37%. Twenty-five percent of the grants and 55% of the funding to colleges of osteopathic medicine were from the National Institutes of Health. Most (63%) grants were awarded to PhD faculty. Most research was conducted in the basic biomedical sciences. Clinical research related to osteopathic practices appears to be a relatively minor component of research at osteopathic medical centers.     

Validation of a laser‐assisted wound measurement device in a wound healing model

In the treatment and monitoring of a diabetic or chronic wound, accurate and repeatable measurement of the wound provides indispensable data for the patient's medical record. This study aims to measure the accuracy of the laser‐assisted wound measurement (LAWM) device against traditional methods in the measurement of area, depth and volume. We measured four ‘healing’ wounds in a Play‐Doh^®‐based model over five subsequent states of wound healing progression in which the model was irregularly filled in to replicate the healing process. We evaluated the LAWM device against traditional methods including digital photograph assessment with National Institutes of Health ImageJ software, measurements of depth with a ruler and weight‐to‐volume assessment with dental paste. Statistical analyses included analysis of variance (ANOVA) and paired t‐tests. We demonstrate that there are significantly different and nearly statistically significant differences between traditional ruler depth measurement and LAWM device measurement, but there are no statistically significant differences in area measurement. Volume measurements were found to be significantly different in two of the wounds. Rate of percentage change was analysed for volume and depth in the wound healing model, and the LAWM device was not significantly different than the traditional measurement technique. While occasionally inaccurate in its absolute measurement, the LAWM device is a useful tool in the clinician's arsenal as it reliably measures rate of percentage change in depth and volume and offers a potentially aseptic alternative to traditional measurement techniques.     

TBI model system grants

The Traumatic Brain Injury (TBI) Model Systems Program has been funded by the National Institute on Disability and Rehabilitation Research (NIDRR) since 1987. Until recently, this program has consisted of four centers that conducted priority-focused research on specific aspects of TBI and analyzed data on the basis of a uniform, comprehensive national database. In 1997, $5 million in additional funding was allocated for the expansion of this program. In October 1998, after a competitive renewal process, a total of 12 new centers were awarded, bringing the total TBI Model Systems to 17. In addition to the creation of new centers, funding was provided for specific collaborative research projects and increased resources for the TBI National Data Center. Below are the abstracts for both the newly funded systems and the existing systems.     

Defense and Veterans Head Injury Program: background and overview

Traumatic brain injury (TBI) is the principal cause of death and disability for young Americans, with an estimated societal cost of over $39 billion per year. The Defense and Veterans Head Injury Program (DVHIP) represents a close collaboration among the Departments of Defense (DoD) and Veterans Affairs (DVA), the Brain Injury Association (BIA), and the International Brain Injury Association (IBIA). Its principal mission is to ensure that military and veteran patients with head injury receive TBI-specific evaluation, treatment, rehabilitation, and follow-up, while at the same time addressing the readiness mission of the military and helping to define optimal care for victims of TBI nationwide. Defense and Veterans Head Injury Program activities can be grouped into three broad classes: (1) TBI education, community service, and primary prevention projects; (2) combined TBI clinical treatment, rehabilitation, and clinical research projects; and (3) clinically linked TBI laboratory research projects. It is thus based on a prudent integration of clinical care and follow-up with programmatic clinical and clinically related laboratory research, TBI prevention, and education. This previously nonexistent clinical infrastructure now offers a valuable base for ongoing TBI clinical research.     

An evaluation of postdoctoral research training and trainees supported by the National Institutes of Health in the Division of Kidney, Urologic and Hematologic Diseases

The interest of young MDs and PhDs in research careers was assessed by determining the number of former trainees who applied for and (or) received research support from the Public Health Service. Thirty-two percent of trainees supported by Institutional Training Grants between 1977 and 1981 made a subsequent application. Seventy-six percent of all those who submitted applications to the National Institutes of Health (NIH) for research project support received awards. Examination of the success rate for individual applications submitted by former trainees showed that 56% of all applications submitted by MD scientists were awarded, and 57% of all applications submitted by PhD scientists were awarded. This compares to an NIH-wide average of 33.3% for the same period. The number of appointments made to Institutional Training Grants for a full year remained fairly constant over a 6-year period, as did the number appointed to individual fellowships over an 8-year period. The dollars expended on Institutional Training Grants increased 33% from 1982 to 1986 for a similar number of trainees, and increased 30% from 1981 to 1988 for a similar number of individual fellowships. The number of Research Career Development Award (RCDA) applications declined by 66% for MDs and by 53% for PhDs, accounting for a 32% reduction in the number of active RCDAs held by MDs and a 60% reduction in active RCDAs held by PhDs from 1985 to 1988. MD scientists submitted more applications, had higher award rates, and received more RCDA awards than did PhD scientists.(ABSTRACT TRUNCATED AT 250 WORDS)     

The history of research training and career awards in urological science supported in the National Institute of Diabetes and Digestive and Kidney Diseases.

Urology research and training grants were placed into a separate research program in 1979. Research emphasis and the context of training programs have changed from a focus on urolithiasis in the 1970s to a broader range of urological disorders in the 1980s. From 1977 to 1990, 49 applications were submitted by 47 applicants for research training/career development support and 39% of the applications were successful. From 1977 to 1987 medical doctors applying for research/career training had a 75% success rate in subsequent National Institutes of Health research grant applications, and basic scientists had a 67% success rate. Of the 33 former trainees supported on institutional training grants during the last 14 years 76% were medical doctors and 24% were basic scientists. From 1977 to 1987, no former medical doctors or basic scientists from institutional training grants have a record of applying to the National Institutes of Health for research grant support. The urology community needs to capitalize on the available opportunities to expand the training programs to increase the number of physician and urological research scientists.     

The impact of combat trauma across the family life cycle: Clinical considerations

Clinical experience and research with veterans of the Second World War and subsequent military conflicts have demonstrated the longstanding nature of combat-related post-traumatic stress disorder and the reverberating effects upon the families of traumatized individuals. The consequences of combat trauma during various stages of family life are discussed. Specifically, the impact upon (a) courtship and mate selection, (b) marriage, (c) childbirth and childrearing, (d) marriage in mid-life, (e) children leaving home, and (f) retirement in late life are reviewed. Finally, clinical considerations for the practice of family psychotherapy in this area are presented.Portions of this paper were presented at the First European Congress of Psychology, Amsterdam, The Netherlands, July 6, 1989. Support for the preparation of this paper was provided by the Medical Research Service of the Department of Veterans Affairs. The opinions expressed in this article are those of the authors and do not necessarily represent those of the Department of Veterans Affairs. The authors extend their gratitude to Drs. Barbara McClure and Harvey A. Taub for their editorial assistance on an earlier version of this article.     

Delivery of plasmid DNA expression vector for keratinocyte growth factor-1 using electroporation to improve cutaneous wound healing in a septic rat model

We have previously shown that wound healing was improved in a diabetic mouse model of impaired wound healing following transfection with keratinocyte growth factor-1 (KGF-1) cDNA. We now extend these findings to the characterization of the effects of DNA plasmid vectors delivered to rats using electroporation (EP) in vivo in a sepsis-based model of impaired wound healing. To assess plasmid transfection and wound healing, gWIZ luciferase and PCDNA3.1/KGF-1 expression vectors were used, respectively. Cutaneous wounds were produced using an 8 mm-punch biopsy in Sprague-Dawley rats in which healing was impaired by cecal ligation-induced sepsis. We used National Institutes of Health image analysis software and histologic assessment to analyze wound closure and found that EP increased expression of gWIZ luciferase vector up to 53-fold compared with transfection without EP (p < 0.001). EP-assisted plasmid transfection was found to be localized to skin. Septic rats had a 4.7 times larger average wound area on day 9 compared with control (p < 0.001). Rats that underwent PCDNA3.1/KGF-1 transfection with EP had 60% smaller wounds on day 12 compared with vector without EP (p < 0.009). Quality of healing with KGF-1 vector plus EP scored 3.0 +/- 0.3 and was significantly better than that of 1.8 +/- 0.3 for treatment with vector alone (p < 0.05). We conclude that both the rate and quality of healing were improved with DNA plasmid expression vector for growth factor delivered with EP to septic rats.     

Halothane hepatitis with renal failure treated with hemodialysis and exchange transfusion

A 38-year-old white female, hepatitis B antigen negative, developed fluminating hepatic failure associated with oliguria and severe azotemia after two halothane anesthesia and without exposure to other hepatotoxic drugs or blood transfusions. She was treated with multiple hemodialysis and exchange blood transfusion. The combined treatment corrected the uremic abnormalities and improved her level of consciousness. The liver and kidney function gradually improved, and she made a complete recovery, the first recorded with hepatic and renal failure under these post-anesthetic conditions. Further evaluation of this combined treatment used for this patient is warranted. Supported by grants from the Veterans Administration; by grants RR-00051 and RR-00069 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health; and by grants AM-07772 and AI-AM-08898 of the United States Public Health Service.