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Natural killer cells (NK) have been associated with the pathophysiology of atopic dermatitis (AD). NK function is regulated by killer cell Ig-like receptor family (KIR) receptors that interact with HLA ligands. The study goal was to focus on allelic variation in genes KIR2DL5, KIR2DS5, and KIR2DS1 with respect to AD. This was a case–control study of individuals with (n = 313) and without (n = 176) AD. Associations were estimated using logistic regression. The prevalence of KIR2DL5 was 52.5% (95% CI 48.0,57.0), KIR2DS5 was 33.0% (28.8,37.3), and KIR2DS1 was 33.6% (29.4,38.0). The presence of the KIR2DL5*001:01 increased the odds of having AD by about 86% (odds ratio (OR): 1.86(1.23,2.82) p = 0.003). The risk for individuals homozygous for KIR2DL5*001:01 was even greater (OR: 2.16 (95% CI 1.31,3.53) p = 0.0023). The odds of having AD with KIR2DL5*001:01 was similar in Whites and Blacks. Allelic variation in KIR2DS5 and KIR2DS1 was not associated with AD. There is no known HLA binding ligand for KIR2DL5. The effect of KIR2DL5*001:01 increased in the presence of HLA-B*-21TT leader sequence (2.46(1.37,4.41) p = 0.0025) and the HLA-C2 ligand (2.07 (1.37,4.41, p = 0.000002). Our study shows an independent association of the KIR2DL5*001:01 with AD and is the first study to associate AD with KIR allelic variation. [ABSTRACT FROM AUTHOR]

The goal of this multicentre study was to evaluate whether circulating endothelial precursor cells and microparticles can predict diabetic foot ulcer healing by the 16th week of care. We enrolled 207 subjects, and 40.0% (28.4, 41.5) healed by the 16th week of care. Using flow cytometry analysis, several circulating endothelial precursor cells measured at the first week of care were associated with healing after adjustment for wound area and wound duration. For example, CD34+CD45dim, the univariate odds ratio was 1.19 (95% confidence interval: 0.88, 1.61) and after adjustment for wound area and wound duration, the odds ratio was (1.67 (1.16, 2.42) p = 0.006). A prognostic model using CD34+ CD45dim, wound area, and wound duration had an area under the curve of 0.75 (0.67, 0.82) and CD34+ CD45dim per initial wound area, an area under the curve of 0.72 (0.64, 0.79). Microparticles were not associated with a healed wound. Previous studies have indicated that circulating endothelial precursor cells measured at the first office visit are associated with a healed diabetic foot ulcer. In this multicentred prospective study, we confirm this finding, show the importance of adjusting circulating endothelial precursor cells measurements by wound area, and show circulating endothelial precursor cells per wound area is highly predictive of a healed diabetic foot ulcer by 16th week of care. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU) are a critical problem for those with diabetes mellitus. Predicting the healing likelihood of a DFU is important to implementing appropriate care, allocating resources, having access to advanced therapies, having successful clinical trials, calibrating clinical trial results, and providing information to administrative entities on patient and provider outcomes. Prognostic modelling can also be important when attempting to compare results across trials or care centres. In a prospective cohort study, we demonstrate and replicate that simple wound characteristics like wound area and wound duration can be used to predict wound healing by the 16th week of care. The models were based on previous literature and replicated using a machine learning algorithm. The use of wound duration and wound area in a prognostic model continues to be important when comparing study results, centre‐based outcomes, as well as designing clinical trials. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a multifactorial pathophysiology. The filaggrin gene (FLG) has particularly been implicated given loss of function (LoF) mutations in this gene lead to skin barrier dysfunction and such mutations can increase a patient's likelihood of developing AD. FLG has intragenic copy number variation (CNV), which impacts the total amount of filaggrin produced. Previous research reported a dose‐dependent effect such that as amount of FLG increases, risk of AD decreases. To gain a better understanding, we evaluated FLG CNV in a large case‐control study of Whites and Blacks with and without AD. The goal of our study was to determine whether FLG CNV has a dose‐dependent effect on the risk of developing AD and to determine whether FLG CNV varies by race. The frequencies and odds ratios comparing a given CNV by race or race within those with AD did not significantly vary. It had been thought that FLG CNV might vary by race and represent an important association with AD in Black AD subjects. However, our work suggests that while there are racial differences with respect to CNV, these differences do not appear to explain AD risk. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a disease of immune dysregulation and skin barrier dysfunction with a relapsing, remitting course and has been associated with several different genetic risk variants. HLA represent a highly variable set of genes that code for cell surface protein molecules involved in the Ag-specific immune response, including the regulation or functioning of T cells, NK cells, and APCs. The purpose of this study was to evaluate associations between HLA class I polymorphisms and the progression of AD over time. We evaluated the associations of AD symptoms and HLA class I polymorphisms based on high-resolution two-field typing in a longitudinal cohort of children with AD (up to 10 y of follow-up). Seven hundred and ninety-two children were evaluated every 6 mo, resulting in 12,752 AD evaluations. Using generalized estimating equations and correctedp values, B*44:02 was found to be associated with AD remission (1.83 [1.35, 2.47];p = 0.0015). The HLA-B residues at position 116 (D-aspartate) and 80 (T-threonine) were associated with remission (1.42 [1.13,1.76],p = 0.003; correctedp = 0.028) and (1.45 [1.17,1.80],p = 0.0008; corrected p = 0.0024), respectively. B80T is a killer-cell Ig-like receptor (KIR) site. Our findings reveal that two axes of immune response (T cell and NK cell) may influence disease progression. Identifying binding pocket changes in addition to other factors (e.g., allergens) that increase the risk or severity of AD can improve our understanding of the immunologic mechanisms associated with AD and may lead to personalized therapies for improving patient care. [ABSTRACT FROM AUTHOR]

Seborrheic dermatitis (SD) is a highly prevalent dermatological condition globally. The condition demonstrates bimodal presentation with what is commonly thought to be two subtypes: adult/adolescent seborrheic dermatitis (ASD) and infantile seborrheic dermatitis (ISD). Despite the common prevalence of ASD and ISD, there remains uncertainty around the underlying pathogenetic mechanisms, risk factors, and appropriate classification of the disease(s). This narrative review summarizes the current understanding of the epidemiology, presentation, and pathogenetic factors like epidermal barrier dysfunction, lipid abnormalities, and cutaneous microbiome for ASD and ISD. Elements such as immune responsiveness, neuroendocrine factors, and genetics in these disease states are also investigated. Throughout our review, we highlight shared features and discrepancies between ASD and ISD that are present in the literature and discuss potential avenues for future research that explore these disease states. We aim to contribute to the medical discourse on ASD and ISD and increase awareness of the need for additional research around these conditions, ultimately informing better targeting of therapeutics moving forward. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a skin disease that results from a combination of skin barrier dysfunction and immune dysregulation. The immune dysregulation is often associated with IgE sensitivity. There is also evidence that autoallergens Hom s 1, 2, 3, and 4 play a role in AD; it is possible that patients with specific HLA subtypes are predisposed to autoreactivity due to increased presentation of autoallergen peptides. The goal of our study was to use in silico epitope prediction platforms as an approach to identify HLA subtypes that may preferentially bind autoallergen peptides and are thus candidates for further study. Considering the previously described association of DRB1 alleles with AD and progression of disease, emphasis was placed on DRB1. Certain DRB1 alleles (08:04, 11:01, and 11:04) were identified by both algorithms to bind a significant percent of the generated autoallergen peptides. Conversely, autoallergen core peptide sequences FRQLSHRFH and IRAKLRLQA (Hom s 1), IRKSKNILF (Hom s 2), FKWVPVTDS and MAAIEKVRK (Hom s 3), and FRYFATLKV (Hom s 4) were predicted to bind many DRB1 alleles and, thus, may play a role in the pathogenesis of AD. Our findings provide candidate DRB1 alleles and autoallergen epitopes that will guide future studies exploring the relationship between DRB1 subtype and autoreactivity in AD. A similar approach can be used for any antigen that has been associated with an IgE response and AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common illness that most commonly originates in childhood, but can be seen in all ages. Filaggrin (FLG) loss of function variants have been associated with the onset and severity of atopic dermatitis and are the most common genetic association with AD. Previous studies have shown variability in the frequency of FLG variants. We have recently demonstrated that previous FLG genotyping methods were inadequate for proper genotyping. In this concise report, we show that genotyping using a popular older informatics program is problematic. In fact, publications that used the older program likely do not properly capture all FLG variants. [ABSTRACT FROM AUTHOR]

Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold‐water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full‐thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double‐blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75–3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, itchy inflammatory skin disorder associated with multiple genetic risk loci [[1]]. The most widely replicated genetic risk factor for AD is loss-of-function (LoF) variants in the filaggrin gene (FLG; NM 002016.2). FLG sequencing from the Genetics of Atopic Dermatitis cohort identified 15 FLG LoF. [Extracted from the article]

Neural imaging benefits from optical access to widespread brain areas. A recent study (Ghanbari et al. Nat. Commun. 2019;10;1500) introduces See-Shell, a transparent polymer skull that reveals the entire dorsal cortex in mice. See-Shells are 3D-printed, customizable, and modifiable for combined neural recording and manipulation, offering advantages for high-resolution, multiscale measures of in vivo brain function. [ABSTRACT FROM AUTHOR]

It is unclear why many with diabetes develop foot ulcers (DFU) and why some do not heal. It could be associated with genetic variation. We have previously shown that NOS1AP variation is associated with lower extremity amputation in those with diabetes and that circulating stem progenitor cell concentration (SPC) is associated with impaired foot ulcer healing in those with diabetes. The goal of this study was to determine if NOS1AP variation is associated with impaired wound healing and with SPC mobilization in those with DFU. In longitudinal cohort study we demonstrate that NOS1AP variants rs16849113 and rs19649113 are associated with impaired wound healing and with SPC mobilization in those with DFU. We believe that further study of NOS1AP is merited and that it NOS1AP might be associated with a functional impairment. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6 months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p = 0.003) for residue 78, 0.27 (0.10, 0.69; p = 0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children. [ABSTRACT FROM AUTHOR]

In the mammalian brain, sensory cortices exhibit plasticity during task learning, but how this alters information transferred between connected cortical areas remains unknown. We found that divergent subpopulations of cortico-cortical neurons in mouse whisker primary somatosensory cortex (S1) undergo functional changes reflecting learned behavior. We chronically imaged activity of S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice learning a texture discrimination task. Mice adopted an active whisking strategy that enhanced texture-related whisker kinematics, correlating with task performance. M1-projecting neurons reliably encoded basic kinematics features, and an additional subset of touch-related neurons was recruited that persisted past training. The number of S2-projecting touch neurons remained constant, but improved their discrimination of trial types through reorganization while developing activity patterns capable of discriminating the animal's decision. We propose that learning-related changes in S1 enhance sensory representations in a pathway-specific manner, providing downstream areas with task-relevant information for behavior. [ABSTRACT FROM AUTHOR]

The burnout literature is replete with burnout score results from quantitative surveys. There is a paucity of qualitative research that seeks to understand the impact of physician stressors on work–life balance and burnout. This study aimed to identify factors that support and disrupt work–life balance, drivers of burnout, and potential solutions among academic dermatologists. The objective was to better understand factors that promote wellness and ameliorate burnout. Concurrent explanatory mixed methods consisted of scores on the Abbreviated Maslach Burnout Inventory and open-ended semi-structured telephone interviews. The results were that positive factors, such as supportive home life and satisfaction derived from academic endeavors, compete with ongoing feelings of exhaustion, frustration, and apathy. Negative stressors include the electronic medical record, insufficient staffing, administrative and clinical task burden, and perceived lack of interest from mid-level and senior health system leadership in addressing clinicians' needs. This was a single-center academic study. As with all qualitative studies, these results may not be generalizable to all dermatologists. In addition, some participants were concerned about their anonymity. Modifiable root causes of burnout require institutional commitment to sustain the pace required by academic dermatologists. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine whether regional variation in the rate of lower-extremity amputation (LEA) is associated with health behaviors. RESEARCH DESIGN AND METHODS This was a cross-sectional prevalence study of merged data from the U.S. Census, Medicare parts A and B, and the Behavioral Risk Factor Surveillance System. We used regression models to determine whether previously described regional variation in LEA incidence was associated with responses to the Behavioral Risk Factor Surveillance System. Regions were created using Dartmouth Atlas Health Referral Regions. RESULTS The mean and median incidence of LEA was 4.5 per 1,000 persons with diabetes; the rate varied from 2.4 to 7.9 LEA per 1,000 persons by health referral region. Statistically significant inverse associations were found between LEA and the rate of patients reporting colorectal screening (P < 0.0001) or the participation in diabetes management classes (P = 0.018). Most other factors, including daily foot evaluations, were not associated with a decreased risk of LEA. These findings were also found to be associated with geographically clustered regions known for increased risk of LEA. CONCLUSIONS LEA is known to vary by region in the U.S., and regions with higher rates of LEA tend to be clustered together. Some of this variation may be explained by health behaviors in those regions, such as attending diabetes education classes or better health prevention habits (e.g., colon cancer screening). It should be possible to prevent unwanted LEAs by educating individuals with diabetes and foot ulcers about the need for participation in foot ulcer treatment. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chronic imaging and electrophysiology offer new insight into cortical map plasticity. [•] Plasticity effects are diverse within local cortical populations. [•] Distinct activity redistributions result from sensory deprivation and learning. [•] Diverse synaptic, intrinsic and compensatory mechanisms likely operate in parallel. [ABSTRACT FROM AUTHOR]

Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs) in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator. [ABSTRACT FROM AUTHOR]

Highlights: [•] We review in vivo chronic extracellular recording and two-photon calcium-imaging studies that address the question of the stability of neuronal population activity. [•] Chronic two-photon calcium imaging has become a powerful tool for analyzing the long-term stability and plasticity of neuronal activity. [•] Sensory cortex contains stable subnetworks of highly active neurons embedded in a sea of relatively unresponsive cells. [•] Throughout the cortex, neuronal activity may be adaptively stabilized by learning. [ABSTRACT FROM AUTHOR]

Objective: Hyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation.Research Design and Methods: This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the "propensity" that an individual was selected to receive HBO.Results: We studied 6,259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care. In the propensity score-adjusted models, individuals receiving HBO were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95% CI 0.63-0.73]) and more likely to have an amputation (2.37 [1.84-3.04]). Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of our results to unmeasured confounding. HBO was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses.Conclusions: Use of HBO neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The usefulness of HBO in the treatment of diabetic foot ulcers needs to be reevaluated. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Hyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation. RESEARCH DESIGN AND METHODS--This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the "propensity" that an individual was selected to receive HBO. RESULTS--We studied 6,259 individuals with diabetes, adequate lower limb arterial perfu-sion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care. In the propensity score-adjusted models, individuals receiving HBO were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95% CI 0.63-0.73]) and more likely to have an amputation (2.37 [1.84-3.04]). Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of our results to unmeasured confounding. HBO was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses. CONCLUSIONS--Use of HBO neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The usefulness of HBO in the treatment of diabetic foot ulcers needs to be reevaluated. [ABSTRACT FROM AUTHOR]

Chronic leg ulcers (as differentiated from wound of the foot) are most often due to venous disease, arterial insufficiency (peripheral arterial disease), or a combination of both. Treatment modalities vary depending on the etiology of the ulcer, so it is important to make an appropriate diagnosis of the wound. Like for most medical illnesses, the determination of the etiology of these wounds is based on history, physical examination, and testing. [ABSTRACT FROM AUTHOR]

Lower extremity amputation ( LEA) is a life-altering complication of diabetes. The goal of our study was to investigate the possibility that genetic variation in neuronal nitric oxide synthase associated protein ( NOS1AP ) is associated with LEA and diabetic peripheral neuropathy ( DPN). Our work used data from the Chronic Renal Insufficiency Cohort ( CRIC) study. CRIC is a multicenter investigation undertaken to pursue the relationship between chronic renal insufficiency and cardiovascular disease. We evaluated 3,040 CRIC study subjects; 1,490 individuals were African Americans and 1,550 were whites. LEA occurred in 162 (5.3%) subjects, 93 (6.2%) of African Americans and 69 (4.4%) of whites. In whites, NOS1AP single nucleotide polymorphism rs1963645 was most strongly associated with LEA (1.73 [1.23, 2.44]). In African Americans three NOS1AP single nucleotide polymorphisms were associated with LEA: rs6659759 (1.65 [1.21, 2.24]); rs16849113 (1.58 [1.16, 2.14]); rs880296 (1.54 [1.14, 2.10]). We tested a subset of 100 CRIC participants for DPN using Semmes- Weinstein filaments. DPN in those with diabetes was associated with rs1963645 (16.97 [2.38, 120.97]) in whites and rs16849113 and rs6659759 (3.62 [1.11, 11.83] and 3.02 [0.82, 11.12], respectively) in African Americans. In conclusion, this is one of the first studies to show that NOS1AP gene variants are associated with DPN and LEA. [ABSTRACT FROM AUTHOR]

Sensory maps are reshaped by experience. It is unknown how map plasticity occurs in vivo in functionally diverse neuronal populations because activity of the same cells has not been tracked over long time periods. Here we used repeated two-photon imaging of a genetic calcium indicator to measure whisker-evoked responsiveness of the same layer 2/3 neurons in adult mouse barrel cortex over weeks, first with whiskers intact, then during continued trimming of all but one whisker. Across the baseline period, neurons displayed heterogeneous yet stable responsiveness. During sensory deprivation, responses to trimmed whisker stimulation globally decreased, whereas responses to spared whisker stimulation increased for the least active neurons and decreased for the most active neurons. These findings suggest that recruitment of inactive, 'silent' neurons is part of a convergent redistribution of population activity underlying sensory map plasticity. Sensory-driven responsiveness is a key property controlling experience-dependent activity changes in individual neurons. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Lower-extremity amputation (LEA) is common among persons with diabetes. The goal of this study was to identify geographic variation and the influence of location on the incidence of LEA among U.S. Medicare beneficiaries with diabetes. RESEARCH DESIGN AND METHODS--We conducted a cohort study of beneficiaries of Medicare. The geographic unit of analysis was hospital referral regions (HRRs). Tests of spatial autocorrelation and geographically weighted regression were used to evaluate the incidence of LEA by HRRs as a function of geographic location in the U.S. Evaluated covariates covered socio-demographic factors, risk factors for LEA, diabetes severity, provider access, and cost of care. RESULTS--Among persons with diabetes, the annual incidence per 1,000 of LEA was 5.0 in 2006, 4.6 in 2007, and 4.5 in 2008 and varied by the HRR. The incidence of LEA was highly concentrated in neighboring HRRs. High rates of LEA clustered in contiguous portions of Texas, Oklahoma, Louisiana, Arkansas, and Mississippi. Accounting for geographic location greatly improved our ability to understand the variability in LEA. Additionally, covariates associated with LEA per HRR included socioeconomic status, prevalence of African Americans, age, diabetes, and mortality rate associated with having a foot ulcer. CONCLUSIONS--There is profound "region-correlated" variation in the rate of LEA among Medicare beneficiaries with diabetes. In other words, location matters and where as the likelihood of an amputation varies dramatically across the U.S. overall, neighboring locations have unexpectedly similar amputation rates, some being uniformly high and others uniformly low. [ABSTRACT FROM AUTHOR]

Chronic venous disease, a disorder involving venous return from the legs, is a growing epidemic in the developed world. Numerous studies have been conducted in the past two decades in an attempt to elucidate its underlying pathophysiology. Many theories have been proposed to address the profound inflammatory dysregulation, with the majority focusing on fibrin trap, inflammatory trap, cytokines, growth factors, and matrix metalloproteinases. Although many of these theories have obtained great momentum, much of the data are contradictory. Moreover, many treatments built on these theories have claimed overwhelming success despite insufficient evidence. At the same time, there are few reviews that critically analyze and evaluate these data. Therefore, in this paper, we will provide summaries of the background data and evolution of these theories and examine their supporting evidence. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Previous studies have shown an association between isotretinoin and inflammatory bowel disease (IBD). The majority of patients prescribed isotretinoin for their acne are previously on an extended course of antibiotics. Therefore, it is important to consider antibiotic use as a confounding variable for the development of IBD.METHODS:We performed a retrospective cohort study using The Health Improvement Network database of the United Kingdom. We identified 94,487 individuals with acne who were followed up by a general practitioner for 406,294 person-years.RESULTS:>A prescription for minocycline was received by 24,085 individuals, for tetracycline/oxytetracycline by 38,603 individuals, and doxycycline by 15,032 individuals. IBD was noted in 41 individuals exposed to minocycline, 79 individuals exposed to tetracycline/oxytetracycline, 32 individuals exposed to doxycycline, and 55 (0.11%) individuals not exposed to any of these antibiotics. The hazard ratio (HR) for developing IBD for any exposure to a tetracycline antibiotic was 1.39 (1.02, 1.90). HRs for individual antibiotics were 1.19 (0.79, 1.79) for minocycline, 1.43 (1.02, 2.02) for tetracycline/oxytetracycline, and 1.63 (1.05, 2.52) for doxycycline. For ulcerative colitis, the associations (HR) were 1.10 (0.76, 1.82) for minocycline, 1.27 (0.78, 2.07) for tetracycline/oxytetracycline, and 1.06 (0.53, 2.13) for doxycycline. For Crohn's disease (CD), the associations (HR) were 1.28 (0.72, 2.30) for minocycline, 1.61 (0.995, 2.63) for tetracycline/oxytetracycline, and 2.25 (1.27 4.00) for doxycycline.CONCLUSIONS:Tetracycline class antibiotics, and particularly doxycycline use may be associated with the development of IBD, particularly CD. Potential confounding by previous doxycycline exposure should be considered when assessing whether treatment with other acne medications increases the risk of IBD. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU) or lower extremity amputation (LEA) are complications of diabetes. In those with diabetes, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are commonly used to prevent the progression of kidney disease. Recent studies have indicated that angiotensin may affect angiogenesis and wound repair. Our goal was to evaluate in those with diabetes the likelihood of developing a DFU or LEA among users of ACEi or ARB using a retrospective cohort design of general practices in the United Kingdom. We studied 40,342 individuals at least 35 years of age with diabetes who were first prescribed ACEi or ARB between 1995 and 2006. A total of 35,153 individuals were treated with ACEi, 12,437 individuals with ARB, and 7,310 both. The hazard ratio for DFU was 0.50 (95% confidence intervals: 0.43, 0.59), showing an increased risk of DFU for those using ACEi vs. ARB. The hazard ratio for LEA was 0.72 (0.48, 1.01). However, among those with lower extremity peripheral arterial disease the hazard ratio was 0.45 (0.22, 0.91) for the new onset of a LEA. In conclusion, among those with diabetes, exposure to ACEi as compared with ARB increases the risk of developing a DFU or LEA. [ABSTRACT FROM AUTHOR]

Retinal ganglion cells (RGCs) are the output cells of the retina; they convert synaptic input into spike output that carries visual information to the brain. Synaptic inputs are received, integrated and communicated to the spike initiation zone of the axon by dendrites whose properties are poorly understood. Here simultaneous patch-clamp recording and 2-photon Ca2+ imaging are used to study voltage- and light-evoked Ca2+signals in the dendrites of identified types of mouse RGCs from parallel ONand OFF pathways, which encode the onset and offset of light, respectively. The results show pathway-specific differences in voltage-dependent Ca2+ signaling. While both ON and OFF cells express high-voltage-activated (HVA) Ca2+channels, only OFF RGCs also express low-voltage-activated (LVA) Ca2+channels. LVA Ca2+ channels in OFF cells are deinactivated by hyperpolarization from the resting potential and give rise to rebound excited Ca2+ spikes at the termination of a step of either hyperpolarizing current or light. This suggests that the differential expression of voltage-gated Ca2+ channels in ON and OFF RGC dendrites contributes to differences in the way the two cell types process visual stimuli. [ABSTRACT FROM AUTHOR]

Venous leg ulcers are a prevalent nonhealing wound of the lower extremity. Although topically applied growth factors successfully improve wound repair in animal studies, similar studies on humans with venous leg ulcers have not been successful. This study was designed to evaluate the acute safety and biologic feasibility of peri-ulcer injection of a replication-incompetent adenoviral construct expressing platelet-derived growth factor-β (PDGF-β). In this phase I study, we demonstrate the initial safety, feasibility, and biologic plausibility of using H5.020CMV.PDGF-β to treat venous leg ulcer disease. [ABSTRACT FROM AUTHOR]

Our objective was to create a practical standardized database of clinically relevant variables in the care of patients with diabetes and foot ulcers. Numerical clinical variables such as age, baseline laboratory values, and wound area were extracted from the wound electronic medical record (WEMR). A coding system was developed to translate narrative data, culture, and pathology reports into discrete, quantifiable variables. Using data extracted from the WEMR, a diabetic foot ulcer-specific database incorporated the following tables: (1) demographics, medical history, and baseline laboratory values; (2) vascular testing data; (3) radiology data; (4) wound characteristics; and (5) wound debridement data including pathology, culture results, and amputation data. The database contains variables that can be easily exported for analysis. Amputation was studied in 146 patients who had at least two visits (e.g., two entries in the database). Analysis revealed that 19 (13%) patients underwent 32 amputations (nine major and 23 minor) in 23 limbs. There was a decreased risk of amputation, 0.87 (0.78, 1.00), using a proportional hazards model, associated with an increased number of visits and entries in the WEMR. Further analysis revealed no significant difference in age, gender, HbA1c%, cholesterol, white blood cell count, or prealbumin at baseline, whereas hemoglobin and albumin were significantly lower in the amputee group ( p<0.05) than the nonamputee group. Fifty-nine percent of amputees had histological osteomyelitis based on operating room biopsy vs. 45% of nonamputees. In conclusion, tracking patients with a WEMR is a tool that could potentially increase patient safety and quality of care, allowing clinicians to more easily identify a nonhealing wound and intervene. This report describes a method of capturing data relevant to clinical care of a patient with a diabetic foot ulcer, and may enable clinicians to adapt such a system to their own patient population. [ABSTRACT FROM AUTHOR]

The article presents a study on the functional effects of pulmonary artery pressure (PAP) in patients with severe chronic obstructive pulmonary disease (COPD). The study utilized cross-sectional and multivariate analysis on 362 COPD patients and measurement of the pulmonary hemodynamics of some test-patients was performed through cardiac catheterization. Results show that functional impact of PAP on COPD patients was observed in their reduced exercise function.

OBJECTIVES: To identify care settings associated with greater pressure ulcer risk in elderly patients with hip fracture in the postfracture period. DESIGN: Prospective cohort study. SETTING: Nine hospitals that participate in the Baltimore Hip Studies network and 105 postacute facilities to which patients from these hospitals were discharged. PARTICIPANTS: Hip fracture patients aged 65 and older who underwent surgery for hip fracture. MEASUREMENTS: A full-body skin examination was conducted at baseline (as soon as possible after hospital admission) and repeated on alternating days for 21 days. Patients were deemed to have an acquired pressure ulcer (APU) if they developed one or more new stage 2 or higher pressure ulcers after hospital admission. RESULTS: In 658 study participants, the APU cumulative incidence at 32 days after initial hospital admission was 36.1% (standard error 2.5%). The adjusted APU incidence rate was highest during the initial acute hospital stay (relative risk (RR)=2.2, 95% confidence interval (CI)=1.3–3.7) and during re-admission to the acute hospital (RR=2.2, 95% CI=1.1–4.2). The relative risks in rehabilitation and nursing home settings were 1.4 (95% CI=0.8–2.3) and 1.3 (95% CI=0.8–2.1), respectively. CONCLUSION: Approximately one-third of hip fracture patients developed an APU during the study period. The rate was highest in the acute setting, a finding that is significant in light of Medicare's policy of not reimbursing hospitals for the treatment of hospital-APUs. Hip fracture patients constitute an important group to target for pressure ulcer prevention in hospitals. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the validity of digital photographs for the assessment of the presence of pressure ulcers stage 2 or higher. Participants were 48 patients (28 white and 20 black) with pressure ulcers identified in the course of a wound specialist's routine clinical practice at the University of Maryland Medical Center. One pressure ulcer and one unaffected skin area were photographed on each participating patient. The gold standard diagnosis (stage 2 pressure ulcer vs. stage 1 or no pressure ulcer) was recorded by the wound specialist based on bedside examination. The photographs were reviewed blindly by another wound expert. The sensitivity of the blinded assessment was 97% (95% confidence interval [CI] 91–100%). The specificity was 97% (95% CI 92–100%). The sensitivity and specificity were both 100% in the white patients. In black patients, the sensitivity and specificity were 92% (95% CI 75–100%) and 93% (95% CI 82–100%), respectively. These results suggest that the use of photographic images to assess the presence or absence of a pressure ulcer stage 2 or higher has a high degree of validity. Since blinded outcome assessment is one of the cornerstones of good clinical trial design, photography offers the potential to strengthen future studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The objective of this study was to evaluate the association between foot ulcers (DFU) and lower-extremity anaputation (LEA) and chronic kidney disease (CKD) in patients with diabetes. RESARCH DESIGN AND METHODS -- This was a retrospective cohort study of individuals enrolled between 2002 and 2006 who were aged ≥35 years, had a history of diabetes, and were cared for in general practice. The physicians participated in The Health Information Network of the U.K. RESULTS -- The presence of DFU or LEA and estimated glomerular filtration rate (eGFR) were evaluated in 90,617 individuals with a median time of observation of 2.4 years. Of these individuals 378 had an LEA and 2,619 had a DFU. CKD (eGFR <60 ml/min per 1.73 m²) was noted in 23,350 (26%) individuals in our cohort. For the development of DFU compared with our reference group (group 1 [eGFR ≥60 ml/min per 1.73 m²]), the hazard ratio (HR) for group 2 (eGFR ≥30 and <60 ml/min per 1.73 m²) was 1.85 (95% CI 1.71-2.01) and for group 3 (eGFR <30 ml/min per 1.73 m²) was 3.92 (3.23-4.75) (all P < 0.001). For LEA, the HR for group 2 was 2.08 (1.68-2.58) and for group 3 was 7.71 (5.29-11.26) (all P < 0.001). CONCLUSIONS -- In this observational study, there is a strong association between stage of CKD and DFU or LEA that is probably not just related to the presence of peripheral arterial disease. Individuals with even moderate CKD (eGFR <60 ml/min per 1.73 m²) have an increased risk for DFU and LEA. [ABSTRACT FROM AUTHOR]

Glutamate released from photoreceptors controls the activity and output of parallel pathways in the retina. When photoreceptors die because of degenerative diseases, surviving retinal networks are left without their major source of input, but little is known about how photoreceptor loss affects ongoing synaptic activity and retinal output. Here, we use patch-clamp recording and two-photon microscopy to investigate morphological and physiological properties of identified types of ON and OFF retinal ganglion cells (RGCs) in the adult (36 -210 d old) retinal degeneration rd-1/rd-1 mouse. We find that strong rhythmic synaptic input drives ongoing oscillatory spike activity in both ON and OFF RGCs at a fundamental "beating" frequency of -10 Hz. Despite this aberrant activity, ON and OFF cells maintain their characteristic dendritic stratification, intrinsic firing properties, including rebound firing in OFF cells, balance of synaptic excitation and inhibition, and dendritic calcium signaling. Thus,RGCs are inherently stable during degeneration-induced retinal activity. [ABSTRACT FROM AUTHOR]

Background. Little is known about the impact of extrinsic factors on pressure ulcer risk. The objective of this study was to determine whether risk of pressure ulcers early in the hospital stay is associated with extrinsic factors such as longer emergency department (ED) stays, night or weekend admission, potentially immobilizing procedures and medications, and admission to an intensive care unit (ICU). Methods. A nested case-control study was performed in two teaching hospitals in Philadelphia, Pennsylvania. Participants were medical patients age ≥65 years admitted through the ED. Cases (n = 195) had ≥ 1 possibly or definitely hospital-acquired pressure ulcers. Three controls per case were sampled randomly from among noncases at the same hospital in the same month (n = 597). Pressure ulcer status was determined by a research nurse on the third day of hospitalization. Pressure ulcers were classified as preexisting, possibly hospital-acquired, or definitely hospital-acquired. Information on extrinsic factors was obtained by chart review. Results. The odds of pressure ulcers were twice as high for those with an ICU stay as for those without (adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI], 1.2-3.5). The aOR was 0.6 (95% CI, 0.3-.9) for use of any potentially immobilizing medications during the early inpatient period. Conclusions. Many of the procedures experienced by patients in the ED and early in the inpatient stay do not confer excess pressure ulcer risk. Having an ICU stay is associated with a doubling of risk. This finding emphasizes the importance of developing and evaluating interventions to prevent pressure ulcers among patients in the ICU. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess alternative statistical methods for estimating relative risks and their confidence intervals from multivariable binary regression when outcomes are common. Study Design and Setting: We performed simulations on two hypothetical groups of patients in a single-center study, either randomized or cohort, and reanalyzed a published observational study. Outcomes of interest were the bias of relative risk estimates, coverage of 95% confidence intervals, and the Akaike information criterion. Results: According to simulations, a commonly used method of computing confidence intervals for relative risk substantially overstates statistical significance in typical applications when outcomes are common. Generalized linear models other than logistic regression sometimes failed to converge, or produced estimated risks that exceeded 1.0. Conditional or marginal standardization using logistic regression and bootstrap resampling estimated risks within the [0,1] bounds and relative risks with appropriate confidence intervals. Conclusion: Especially when outcomes are common, relative risks and confidence intervals are easily computed indirectly from multivariable logistic regression. Log-linear regression models, by contrast, are problematic when outcomes are common. [Copyright &y& Elsevier]

Neuronal discharge is driven by either synaptic input or cell-autonomous intrinsic pacemaker activity. It is commonly assumed that the resting spike activity of retinal ganglion cells (RGCs), the output cells of the retina, is driven synaptically, because retinal photoreceptors and second-order cells tonically release neurotransmitter. Here we show that ON and OFF RGCs generate maintained activity through different mechanisms: ON cells depend on tonic excitatory input to drive resting activity, whereas OFF cells continue to fire in the absence of synaptic input. In addition to spontaneous activity, OFF cells exhibit other properties of pacemaker neurons, including subthreshold oscillations, burst firing, and rebound excitation. Thus, variable weighting of synaptic mechanisms and intrinsic properties underlies differences in the generation of maintained activity in these parallel retinal pathways. [ABSTRACT FROM AUTHOR]

To evaluate the ability of research nurses to identify pressure ulcers, the authors assembled digital photographs of the skin of 160 consenting elderly patients (80% African American, 63% women). The series included 39 photos of pressure ulcers, 109 of normal skin, and 12 of other skin conditions, determined by consensus by two experts (D.J.M. and S.H.K.). Photos were packaged electronically into eight blocks of 20, with pressure ulcer prevalence ranging from 20% to 30% per block. The eight blocks were duplicated to create two sets of 160 photos each. Each of six raters (experienced clinical research nurses), working independently, evaluated the 320 photos as if each photo depicted a different patient. For analysis, the ratings were collapsed into binary determinations (any pressure ulcer vs. none). The overall sensitivity and specificity of the ratings were 0.97 (95% confidence interval: 0.94, 0.98) and 0.81 (95% confidence interval: 0.77, 0.86), respectively. Rater-specific prevalence (range: 31.8–47.5%) exceeded the true prevalence (24.4%). Inter- and intrarater reliability coefficients were 0.69 and 0.84, respectively. Trained research nurses can accurately classify pressure ulcers from photographs, even when patients are largely non-White and the photographs depict pressure ulcers spanning all pressure ulcer stages. [ABSTRACT FROM AUTHOR]

Background. Pressure ulcers among elderly hospital patients diminish quality of life and increase the cost of hospital care. Evidence suggests that pressure ulcers can arise after only a few hours of immobility. The goals of this study were to estimate the incidence of hospital-acquired pressure ulcers in the first 2 days of the hospital stay and to identify patient characteristics associated with higher incidence. Methods. A prospective cohort study was performed between 1998 and 2001. A total of 3233 patients 65 years old or older admitted through the Emergency Department to the inpatient Medical Service at two study hospitals were examined by a research nurse on the third day of hospitalization. Pressure ulcers were ascertained using standard criteria and were classified as either preexisting, possibly hospital-acquired, or definitely hospital-acquired. Results. There were 201 patients with one or more possibly or definitely hospital-acquired pressure ulcers for a cumulative incidence of 6.2% (95% confidence interval, 5.4%-7.1%). Most of the pressure ulcers were stage 2, and the majority were in the sacral area or on the heels. In multivariable analysis, pressure ulcer incidence was significantly associated with increasing age, male gender, dry skin, urinary and fecal incontinence, difficulty turning in bed, nursing home residence prior to admission, recent hospitalization, and poor nutritional status. Conclusions. A small but significant proportion of elderly emergently admitted hospital patients acquire pressure ulcers soon after their admission. New models of care may be required to ensure that preventive interventions are provided very early in the elderly person's hospital stay. [ABSTRACT FROM AUTHOR]

The goal of this study was to estimate the effectiveness in actual clinical practice of recombinant human platelet-derived growth factor (rhPDGF) for the treatment of diabetic neuropathic foot ulcer (DNFU). Previously published pivotal trials have shown that by the 20th week of care 35 percent more ulcers healed in the group randomized to receive rhPDGF than those who did not receive rhPDGF (i.e., a relative risk [RR] of about 1.35). This represents an estimate of the efficacy of rhPDGF under the tightly controlled conditions of randomized clinical trials. Treatment effectiveness under standard clinical practice was estimated in a retrospective cohort study, controlling for treatment selection bias using propensity scores. We noted 24,898 individuals with a DNFU, of whom 9.6 percent received rhPDGF. We successfully created a propensity score model that evenly balanced many wound characteristics between those who received rhPDGF and those who did not. We created five groups, which varied from those least likely to receive rhPDGF to those most likely to receive rhPDGF. The RR, controlling for the propensity, to receive rhPDGF for a healed wound after treatment with rhPDGF as compared with standard care was 1.32 (1.22, 1.38). With respect to amputation, the RR for undergoing amputation after receiving rhPDGF was 0.65 (0.54, 0.78) as compared with those who did not receive rhPDGF. Within the limitations of our study, rhPDGF is more effective than standard therapy in both helping a wound to heal and preventing amputation, and its effect is similar to the efficacy estimates from previously published randomized controlled trials. [ABSTRACT FROM AUTHOR]

A neuropathic foot ulcer is a severe complication of diabetes that can result in a more severe complication, a lower extremity amputation. We conducted a cohort study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within a multicenter wound care network. A total of 1653 (6.7%) individuals had an amputation and 46.3% of these amputations were of a toe or ray (minor amputation). In the more than 10-year follow-up period that we studied, the percentage of those who had an amputation varied between 5.6% and 8.4%. Of those who had an amputation, the percentage that had a minor amputation increased over time from 4.0% in the earliest years to more than 60% in the later years of observation. The single most important determinant of amputation was the observation of fascia, tendon, and bone at the initial assessment. In conclusion, about 7% of those with a diabetic neuropathic foot ulcer will have an amputation and in the past 10 years there has been a remarkable increase in the number of minor as compared to major amputations. [ABSTRACT FROM AUTHOR]

Venous leg ulcers are among the most common chronic wounds. Treatment is commonly with a limb compression bandage. Previous small, often single-center, studies have shown that it is possible to predict which wounds are likely to respond to compression therapy. We designed this cohort study using a dataset of over 20,000 individuals with a venous leg ulcer to investigate the accuracy of several prognostic models. Creating complex models using logistic regression, as well as simply counting prognostic factors, we show that initial measures of wound size and duration accurately predict, as measured by area under the receiver operator curve and Brier score, who will heal by the 24th week of care. For example, a wound that is less than 10 cm2 and less than 12 months old at the first visit has a 29 percent chance of not healing by the 24th week of care, while a wound greater than 10 cm2 and greater than 12 months old has a 78 percent chance of not healing. Ultimately, these models can be applied by a clinician to help determine whom to continue to treat with standard care and perhaps whom to treat with adjuvant therapies. They may also aid in the design of clinical trials. [ABSTRACT FROM AUTHOR]

: PurposeNeuropathic foot ulcers are a serious complication of diabetes. The purpose of this study was to develop a clinically useful prognostic model for identifying ulcers that are not likely to heal.: MethodsUsing an administrative and medical records database from a large wound care system, we designed a cohort study of patients with diabetic neuropathic foot ulcer. Clinicians followed a standard algorithm of good wound care, wound de´bridement, and wound offloading. The outcome was a healed wound by week 20 of care. For patients with more than one wound, we investigate the wound labeled as the primary wound. We evaluated several prognostic models of varying mathematical complexity.: ResultsWe studied 27,630 patients with a diabetic neuropathic foot ulcer, of whom 12,983 (47%) healed by week 20 of care. The simplest model counted 1 point each if the wound was older than 2 months, larger than 2 cm2, or had a grade ≥3 (on a 6-point scale). The likelihood that a wound would not heal was 0.35 for a count of 0, 0.47 for a count of 1, 0.66 for a count of 2, and 0.81 for a count of 3 in the validation data set.: ConclusionA simple prognostic model can be developed using prognostic factors that are already part of the wound care examination. Applications of this model could include determining who will do well with standard care and as an aid in the design of clinical trials. [Copyright &y& Elsevier]

Objective: The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care.Research Design and Methods: This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated.Results: Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care.Conclusions: The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful. [ABSTRACT FROM AUTHOR]

Evaluates the association of certain medical conditions in older ambulatory patients with the risk of developing a pressure ulcer. Methodology; Results of the study; Discussion of study findings.

OBJECTIVE -- The goal of this study was to evaluate whether simple risk factors can be identified that successfully characterize who will heal and who will not heal among patients who have received standard therapy for diabetic neuropathic foot ulcers. RESEARCH DESIGN AND METHODS -- For this cohort study, we evaluated >31,000 individuals with a diabetic neuropathic foot ulcer seen in the Curative Health Services System. Using multivariate logistic regression, we evaluated the association between wound size, wound duration, wound grade, and other variables and their effect on whether a patient would heal by the 20th week of care. RESULTS -- We demonstrated that wound size, wound duration, and wound grade are all significantly associated with the likelihood of a wound healing by the 20th week of care. In addition, we noted that these associations were not significantly affected by the treating wound care center, whether the unit of analysis was one wound on a patient or all of their wounds, or current adjuvant therapies. CONCLUSIONS -- We have shown that three easy-to-measure risk factors are associated with a wound healing. These results should help clinicians understand the likelihood that a wound will heal and help those conducting clinical investigations to design better trials. [ABSTRACT FROM AUTHOR]

PURPOSE: The objective of this study was to estimate the period prevalence and incidence of pressure ulcer among those 65 years of age and older.METHODS: We used a patient-record database called the General Practice Research Database (GPRD). Subjects were 65 years of age and older and cases were ascertained based on strict inclusion and exclusion criteria. The accuracy of the ascertainment strategy was estimated using mailed physician-answered questionnaires. Annual period prevalence and age-specific incidence were estimated per 100 person-years with exact 95% confidence intervals (CI).RESULTS: The accuracy of our ascertainment strategy was excellent, with a positive predictive value of 100% (95% CI: 92%,100%) and negative predictive value of 95% (85%, 95%). Over 200,000 person-years of data were analyzed. The annual period prevalence of pressure ulcer among those 65 years of age and older varied from 0.31% to 0.70%. The incidence varied significantly with advancing patient age from 0.18 to 3.36 per 100-person years (p < 0.001) but was not associated with gender (p = 0.95).CONCLUSIONS: Pressure ulcers are seen in the general practice setting. They are most likely to occur in those over 85 years of age. Preventative strategies within the general practice setting should concentrate on the oldest of the elderly. [Copyright &y& Elsevier]