Topical α-Gal Nanoparticles Enhance Wound Healing in Radiated Skin.

PURPOSE: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galß1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues. METHODS: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding. RESULTS: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration. CONCLUSIONS: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.

Examining Cross-Country and Sex Differences on a Comprehensive Assessment of Protective Behavioral Strategies for Alcohol.

OBJECTIVE: Use of protective behavioral strategies (PBS) has been associated with reduced alcohol-related harms among college students. However, most of this research has been conducted among U.S. samples. The present study examines the use of PBS in an international context. METHOD: Participants (n = 1512) were recruited from universities in Spain (n = 298), Argentina (n = 439), and the U.S. (n = 775) to determine if there are differences in PBS use across countries and/or across sex. Further, we examined whether the association between PBS use and negative consequences differ across country and sex. RESULTS: We found that U.S. students reported the most frequent use of Stopping/Limiting Drinking PBS (M = 3.32, SD = 1.23) compared to Argentine (M = 2.89, SD = 0.97) and Spanish (M = 2.83, SD = 0.94) students. Argentine students reported the least frequent use of Serious Harm Reduction PBS (M = 4.57, SD = 0.99) compared to U.S. (M = 5.09, SD = 0.98) and Spanish (M = 5.03, SD = 0.78) students. Elastic net regression analyses stratified by country indicated most individual PBS predicted decreased negative alcohol-related consequences, although two items consistently predicted increased consequences and we observed some variability in the most predictive specific strategies in each country. Across each subscale and for 32 of 40 individual items, females reported more frequent use of PBS than males (ps<.05). CONCLUSIONS: From the perspective of developing and adapting interventions, we recommend the cultural context in which PBS are used is taken into account. Although future work is needed to delineate cultural factors underlying the country-level differences we found, these findings have implications for the most promising PBS to target for college students in each country.

Dynamic sensory cues shape song structure in Drosophila.

The generation of acoustic communication signals is widespread across the animal kingdom, and males of many species, including Drosophilidae, produce patterned courtship songs to increase their chance of success with a female. For some animals, song structure can vary considerably from one rendition to the next; neural noise within pattern generating circuits is widely assumed to be the primary source of such variability, and statistical models that incorporate neural noise are successful at reproducing the full variation present in natural songs. In direct contrast, here we demonstrate that much of the pattern variability in Drosophila courtship song can be explained by taking into account the dynamic sensory experience of the male. In particular, using a quantitative behavioural assay combined with computational modelling, we find that males use fast modulations in visual and self-motion signals to pattern their songs, a relationship that we show is evolutionarily conserved. Using neural circuit manipulations, we also identify the pathways involved in song patterning choices and show that females are sensitive to song features. Our data not only demonstrate that Drosophila song production is not a fixed action pattern, but establish Drosophila as a valuable new model for studies of rapid decision-making under both social and naturalistic conditions.

The Price of Aesthetics After Nipple-Sparring Mastectomy: A Cost-Minimization Analysis of Skin Banking With Deep Inferior Epigastric Perforator Flap.

BACKGROUND: Skin necrosis after nipple-sparing mastectomy (NSM) and deep inferior epigastric perforator (DIEP) breast reconstruction impacts cosmesis and patient satisfaction. Skin grafting might mitigate these sequelae, but oftentimes creates a color and texture mismatch with native breast skin. In contrast, abdominal skin on the DIEP flap is an excellent match and can be banked. The purposes of this study are to review our experience with skin banking of DIEP flaps and determine the cost-benefit of skin banking compared with other reconstructive options. METHODS: This was a retrospective review study conducted from 2011 to 2014 to examine patients undergoing staged DIEP reconstruction immediately after NSM. Medicare reimbursement costs using Current Procedural Terminology codes, and provider and facilities fees for conventional reconstructions options versus skin banking were obtained with subsequent cost-minimization and sensitivity analyses. RESULTS: The proportion of patients who developed mastectomy skin necrosis was 12.1%, and that of those who had a positive retroareolar biopsy corresponding to an average surface area of 58.3 cm was 3.0%. Average per patient cost of skin banking was $1224, $844 more than split-thickness skin graft (STSG) without Integra, $420 more than STSG with Integra, and $839.01 more than full-thickness skin graft. Sensitivity analysis demonstrates that skin banking was less than managing mastectomy skin loss with STSG and Integra when the incidence of necrosis >10 cm exceeded 25.3%. CONCLUSIONS: Skin banking maximizes aesthetic outcomes after skin loss from either positive margins or skin flap necrosis. Use of this technique should occur especially in select patients at increased risk of mastectomy skin flap/nipple-areola complex (NAC) necrosis and/or suspicion for occult NAC carcinoma. Furthermore, among reconstructive plastic surgeons whose rate of mastectomy flap/NAC necrosis >10 cm exceeds 25.3%, sensitive analysis favors undergoing a staged reconstruction after NSM.

The importance of indocyanine green near-infrared fluorescence angiography in perfusion assessment in vascularized omentum lymphatic transplant.

BACKGROUND AND OBJECTIVE: Vascularized omentum lymphatic transplant (VOLT) for treatment of lymphedema has become popular because of no risk of iatrogenic lymphedema and abundant lymphatic tissue. However, perfusion to the omentum can be difficult to assess clinically. The purpose of this study was to clarify the incidence and degree of ischemia in the omentum. METHODS: A retrospective study was conducted to review indocyanine green perfusion findings on patients undergoing VOLT. Patients were placed into 4 categories based on the percentage surface area of omentum that was ischemic: normal, less than 25%, between 25% and 50%, and greater than 50% ischemic. Spearman correlation was performed to determine whether an association exists between prior abdominal surgery and the presence of ischemia. RESULTS: Twenty-six patients underwent VOLT for treatment of extremity lymphedema. Twelve (46.2%) patients had normal perfusion, 8 patients (30.8%) had less than 25% ischemia, and 6 patients (23.1%) had 25% to 50% ischemia. Prior abdominal surgery was not significantly associated with the presence of ischemia. CONCLUSIONS: Normal flap perfusion is a requisite for successful VOLT harvest. However, over half the patients had some degree of abnormal perfusion irrespective of prior abdominal surgery. Indocyanine green angiography is an important tool in ensuring a healthy lymphatic reconstruction.

Risk factors of infected sternal wounds versus sterile wound dehiscence.

BACKGROUND: Sterile sternal dehiscence (SSD) and sternal wound infections (SWIs) are two complications of median sternotomy with high rates of morbidity. Sternal wound complications also carry significant economic burden, almost tripling patients' hospital costs and are considered a nonreimbursable "never event" for Medicare. Historically, SDD and SWI have been recognized as discrete entities, but nonetheless continue to be categorized as a singular complication in literature. The purpose of this study was to determine specific patient demographic and perioperative predictors of SSD and SWI. MATERIALS AND METHODS: An institutional review board-approved, retrospective study of 8098 consecutive patients who underwent cardiac surgery at Columbia University Medical Center between January 2008 and December 2013 was conducted. Patients were categorized into three groups: no sternal wound complication, SSD, or SWI. Statistical analysis was performed using univariate and multivariate logistic regression analysis. RESULTS: Of 8098 patients, there were 73 patients (0.9%) with SSD and 40 (0.5%) with SWI who required plastic surgical consultation, debridement, and flap closure. In univariate analysis of SSD, positive predictors (i.e., "risk" factors) were age >42 years, prior surgery this admission, ≥2 arterial conduits, internal mammary artery (IMA) grafting with or without previous IMA grafting, body mass index (BMI) >30 (obese), CHF, diabetes requiring medication, respiratory failure, and unplanned cardiac reoperation; negative predictors (i.e., "protective" factors) were no arterial conduits and extubation within 24 h. In univariate analysis of SWI, positive predictors were IMA grafting with or without previous IMA grafting, postoperative hematocrit urgent/emergent surgical priority, BMI >30 (obese), cardiac ejection fraction <40%, and respiratory failure; negative predictors were no arterial conduits and elective surgical priority. In multivariate regression, BMI >30, diabetes requiring medication, and respiratory failure were determined to be significant positive predictors of SSD, and IMA grafting with or without prior IMA grafting and respiratory failure were significant positive predictors for SWI; no significant negative predictors were identified. CONCLUSIONS: This study found that SSD and SWI have many common significant predictors consistent with findings that increased BMI, use of IMA grafts, poor cardiac reserve, and postoperative respiratory failure confer increased risk of sternal wound complications. Additionally, this study also found that there were predictors unique to each entity supporting that SSD and SWI may be related but are not a singular entity. Recognition and prevention of significant positive and negative predictors of SSD and SWI may be valuable in preoperative counseling, operative planning, and postoperative management. Although sternal wound complications can be successfully managed by plastic surgical intervention, preventing the development of median sternotomy complications may curb costs incurred by both patients and health care systems.

Perioperative Antibiotics in the Setting of Oropharyngeal Reconstruction: Less Is More.

BACKGROUND: Recipient-site infection after oropharyngeal reconstruction is a potentially disastrous complication. Although studies suggest that perioperative antibiotics reduces infection rates in these patients from 87% to 20%, there is no consensus regarding what constitutes the most appropriate antibiotic regimen and duration of treatment. METHODS: A retrospective review of perioperative antibiotic administration was performed of all patients who underwent local, pedicled, or free flap oropharyngeal reconstruction after oncologic resection by a single surgeon at a single institution between 2007 and 2013 to assess for recipient-site complications. RESULTS: Ninety-seven patients underwent 100 reconstructions (61 free flap reconstructions, 39 pedicled/local flap reconstructions) and all received a combination of intravenous (IV) antibiotic agents designed to cover oral flora. There were 23 (23%) recipient-site complications, which included cellulitis (9%), mucocutaneous fistula (5%), abscess (5%), and wound dehiscence (4%). Duration of antibiotic prophylaxis, defined as less than 48 hours (short-course) or greater than 48 hours (long-course), was not a significant predictor of recipient-site complication. Significant risk factors for recipient-site complications were clindamycin prophylaxis (P < 0.008), increased duration of surgery (P < 0.047), and advanced age (P < 0.034). Recipient-site complication was found to be a significant predictor of both increased length of hospital stay (P < 0.001) and increased time to the resumption of enteral feeds (P < 0.035). CONCLUSIONS: These data suggest that extended courses of perioperative antibiotics do not confer additional benefits in patients undergoing oropharyngeal reconstruction. We recommend a limited 48-hour course of prophylactic antibiotics with sufficient aerobic and anaerobic coverage to help minimize the incidence of antibiotic-related morbidities.

Improving adherence to asthma therapies.

PURPOSE OF REVIEW: Adherence to asthma therapies is poor leading to unnecessary morbidity and increased use of emergency and hospital resources. Strategies to improve adherence have not been successful. RECENT FINDINGS: Asthma adherence disease management is a clinical method to improve adherence for asthma patients. The method includes: diagnosing adherence status; identifying patient barriers leading to nonadherence; selecting specific strategies for the clinician for each barrier identified; use of patient-centered communication skills to enhance the effectiveness of the strategies employed. This approach is now being tested in multiple controlled trials. SUMMARY: Clinicians may want to consider these strategies, in whole or in part, to improve asthma patient adherence.

Acellular dermal matrix-based gene therapy augments graft incorporation.

BACKGROUND: Acellular dermal matrix (ADM) is widely used for structural or dermal replacement purposes. Given its innate biocompatibility and its potential to vascularize, we explored the possibility of ADM to function as a small interfering RNA (siRNA) delivery system. Specifically, we sought to improve ADM vascularization by siRNA-mediated inhibition of prolyl hydroxylase domain-2 (PHD2), a cytoplasmic protein that regulates hypoxia inducible factor-1α, and improve neovascularization. MATERIALS AND METHODS: Fluorescently labeled siRNA was used to rehydrate thin implantable ADM. Pharmacokinetic release of siRNA was determined. Twelve millimeter sections of ADM reconstituted with PHD2 siRNA (nonsense siRNA as control) and applied to dorsal wounds of 40 FVB mice. Grafts were sewn in, bolstered, and covered with occlusive dressings. Photographs were taken at 0, 7, and 14 d. Wounds were harvested at 7 and 14 d and analyzed (messenger RNA, protein, histology, and immunohistochemistry). RESULTS: Release kinetics was first-order with 80% release by 12 h. By day 14, PHD2-containing ADM appeared viable and adherent, whereas controls appeared nonviable and nonadherent. Real-time reverse transcription-polymerase chain reaction demonstrated near-complete knockdown of PHD2, whereas vascular endothelial growth factor and FGF-2 were increased 2.3- and 4.7-fold. On enzyme-linked immunosorbent assay, vascular endothelial growth factor was increased more than fourfold and stromal cell-derived factor doubled. Histology demonstrated improved graft incorporation in treated groups. Immunohistochemical demonstrated increased vascularity measured by CD31 staining and increased new cell proliferation by denser proliferating cell nuclear antigen staining in treated versus controls. CONCLUSIONS: We concluded that ADM is an effective matrix for local delivery of siRNA. Strategies to improve the matrix and/or genetically alter the local tissue environment can be envisioned.

Normalizing dysfunctional purine metabolism accelerates diabetic wound healing.

Diabetic patients exhibit dysfunction of the normal wound healing process, leading to local ischemia by vascular occlusive disease as well as sustained increases in the proinflammatory cytokines and overproduction of reactive oxygen species (ROS). Of the many sources of ROS, the enzyme xanthine oxidase (XO) has been linked to overproduction of ROS in diabetic environment, and studies have shown that treatment with XO inhibitors decreases XO overactivity and XO-generated ROS. This study evaluates the role of XO in the diabetic wound and the impact of specifically inhibiting its activity on wound healing. Treatment of diabetic wounds with siXDH (xanthine dehydrogenase siRNA) decreased XDH mRNA expression by 51.6%, XO activity by 35.9%, ROS levels by 78.1%, pathologic wound burden by 31.5%, and accelerated wound healing by 7 days (23.3%). Polymerase chain reaction analysis showed that increased XO activity in wild-type wound may be due to XDH to XO conversion and/or XO phosphorylation, but not to gene transcription, whereas increased XO activity in diabetic wounds may also be from gene transcription. These results suggest that XO may be responsible for large proportion of elevated oxidative stress in the diabetic wound environment and that normalizing the metabolic activity of XO using targeted delivery of siXDH may decrease overproduction of ROS and accelerate wound healing in diabetic patients.

Postoperative Expansion is not a Primary Cause of Infection in Immediate Breast Reconstruction with Tissue Expanders.

Perioperative infection is the most common and dreaded complication associated with tissue expander (TE) breast reconstruction. Historically, the expansion period was thought to be the time of greatest hazard to the implant. However, recent institutional observations suggest infectious complications occur prior to expansion. This investigation, therefore, was conducted to determine the timing of infectious complications associated with two-stage TE breast reconstructions. Following IRB approval, a retrospective review of all consecutive two-stage immediate TE breast reconstructions at a single institution from November 2007 to November 2011 was conducted. Reconstructions were then divided into two cohorts: those suffering infectious complications and those that did not. Infectious complications including minor cellulitis, major cellulitis, abscess drainage, and explantation were identified. Various operative and patient variables were evaluated in comparison. Eight hundred ninety immediate two-stage TE breast reconstructions met inclusion criteria. Patients suffering infection were older (55.4 years versus 49.3 years; p < 0.001), and more likely to have therapeutic mastectomy (94% versus 61%; p < 0.0001), the use of acellular dermal matrix (ADM; 72.5% versus 54.9%; p = 0.001), and greater initial TE fill (448.6 mL versus 404.7 mL; p = 0.0078). The average time to developing of infectious symptoms was 29.6 days (range 9-142 days), with 94.6% (n = 87) of infections prior to the start of expansion. Perioperative infections in immediate two-stage TE to implant breast reconstructions are significant and occur mostly prior to the start of expansion. Thus, challenging the conventional wisdom that instrumentation during expander filling as the primary cause of implant infections. Possible etiologic factors include greater age, therapeutic mastectomy versus prophylactic mastectomy, larger initial TE fill, and the use of ADM.

Thrombin and topical local anesthetic for postoperative pain management.

PURPOSE: Local anesthetic is often used for perioperative pain control. Thrombin serves as a carrying medium for sustained release of antibiotics, chemotherapy, and growth factors. We tested the hypothesis that local anesthetic pain relief can be prolonged with the adjunct use of thrombin. METHODS: A prospective single-blinded clinical study was performed. Patients undergoing elective hand surgery inclusive of carpal tunnel release, excision of ganglion cyst, trigger finger release, and excision of mucous cyst under local block were enlisted. Before closure, patients received 1 of the following combinations: (1) control with oral analgesics, (2) 5 mL of 2% xylocaine, (3) 5 mL of 0.5% bupivacaine, (4) 2.5 mL of 2% xylocaine with 2.5 mL of 0.5% bupivacaine (XB), (5) thrombin with 5 mL of 2% xylocaine (XT), (6) thrombin with 5 mL of 0.5% bupivacaine (BT), and (7) thrombin with 2.5 mL of 2% xylocaine and 2.5 mL of 0.5% bupivacaine (XBT). There were 7 patients in each group, and patient demographics were similar between groups. Outcome measures included postanesthesia care unit (PACU) time, pain level, and number of pain pills required. RESULTS: Compared with oral analgesics alone, mean (SD) postoperative pain levels were reduced by 33.3% (8.9%) by xylocaine, 69.1% (8.7%) by bupivacaine, and 45.7% (9.4%) by XB. When thrombin was added, pain levels were further reduced by 69.9% by XT (P < 0.001), 23.1% by BT (P = 0.071), and 50.5% by XBT (P < 0.001) compared with their nonthrombin counterparts. In addition, PACU time was decreased by 34.8% by XT (P = 0.003) and 19.7% by XBT (P = 0.013) compared with xylocaine and XB, respectively. However, there was no difference in total pain pills needed between xylocaine, bupivacaine, and XB when administered with and without thrombin. CONCLUSIONS: The addition of topical thrombin to local anesthetic at the end of elective hand surgery provides for sustained postoperative pain control. Patients in this study who received thrombin and local anesthetic before wound closure had lower pain levels and were discharged from the PACU sooner than those who received local anesthetic alone. LEVEL OF EVIDENCE: Therapeutic level 2.

A prospective analysis of the association between indwelling surgical drains and surgical site infection in plastic surgery.

INTRODUCTION: Many surgeons fear that closed-suction drains serve as a portal for bacterial entry into surgical spaces. Despite a lack of supporting evidence, postoperative antibiotics are often prolonged while drains remain in place. METHODS: Medical records of all patients who underwent intraoperative Jackson-Pratt drain placement and sterile removal over a 12-month period were prospectively analyzed. RESULTS: Fifty-four patients with 101 drains were included. Drains were in place for 5 to 43 days [mean (SD), 13.5 (6.3) days]. Sixty-three percent of drains had positive cultures. All patients received perioperative antibiotics. Thirty-nine patients received postoperative antibiotics [mean (SD), 13.8 (13.8) days]. There were 2 cases of cellulitis. One patient required reoperation. CONCLUSIONS: Sixty-six drains (65.3%) were placed in the presence of prosthetic material. Although nearly two thirds of drains were colonized with bacteria, our wound infection rate was extremely low (5.6%). Thus, closed-suction drains may be left in place for an extended period without increasing the risk of infection, even in the presence of prosthetic material.

Religion and drinking: Differences between two campuses.

Levels of religiousness vary by geographic location, but studies of the relationship between religiousness and alcohol are often limited to one region. For our participants (N = 1124; 57.5% female), location was significantly associated with both religiousness and alcohol use. Active religiousness was associated with drinking outcomes. The indirect effects of location on drinks per week through active religiousness were significant. At Campus S, subjective religiousness was associated with more drinks per week, whereas active religiousness was associated with fewer drinks per week. Findings indicate active religiousness is especially relevant when exploring drinking, and location is important when exploring religiousness and alcohol use.

Therapeutic delivery of hydrogen sulfide for salvage of ischemic skeletal muscle after the onset of critical ischemia.

BACKGROUND: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury (IRI). METHODS: This study evaluated the potential utility of hydrogen sulfide in preventing IRI in skeletal muscle by using in vitro (cultured myotubes subjected to sequential hypoxia and normoxia) and in vivo (mouse hind limb ischemia, followed by reperfusion) models to determine whether intravenous hydrogen sulfide delivered after the ischemic event had occurred (pharmacologic postconditioning) conferred protection against IRI. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotide transferase-mediated deoxy-uridine triphosphate nick-end labeling, respectively. RESULTS: In vitro, hydrogen sulfide reduced the apoptotic index after 1, 3, or 5 hours of hypoxia by as much as 75% (P = .002), 80% (P = .006), and 83% (P < .001), respectively. In vivo, hydrogen sulfide delivered after the onset of hind limb ischemia and before reperfusion resulted in protection against IRI-induced cellular changes, which was validated by significant decreases in the injury score and apoptotic index. The timing of hydrogen sulfide delivery was crucial: when delivered 20 minutes before reperfusion, hydrogen sulfide conferred significant cytoprotection (P < .001), but treatment 1 minute before reperfusion did not provide protection (P = NS). CONCLUSIONS: These findings confirm that hydrogen sulfide limits IRI-induced cellular damage in myotubes and skeletal muscle, even when delivered after the onset of ischemia in this murine model. These data suggest that when given in the appropriate dose and within the proper time frame, hydrogen sulfide may have significant therapeutic applications in multiple clinical scenarios.

Topical prolyl hydroxylase domain-2 silencing improves diabetic murine wound closure.

Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia-inducible factor (HIF)-1α stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1α, rendering it inactive. However, in hypoxia, PHD2 is inactive, HIF-1α is stabilized and downstream effectors such as vascular endothelial growth factor and fibroblast growth factor-2 are produced to promote angiogenesis. In the present study we utilize RNA interference to PHD2 to promote therapeutic angiogenesis in a diabetic wound model, presumably by the stabilization of HIF-1α. Stented wounds were created on the dorsum of diabetic Lepr db/db mice. Mice were treated with PHD2 small interfering RNA (siRNA) or nonsense siRNA. Wounds were measured photometrically on days 0-28. Wounds were harvested for histology, protein, and RNA analysis. Diabetic wounds treated with siRNA closed within 21±1.2 days; sham-treated closed in 28±1.5 days. By day 7, Western blot revealed near complete suppression of PHD protein and corresponding increased HIF-1α. Angiogenic mediators vascular endothelial growth factor and fibroblast growth factor-2 were elevated, corresponding to increased CD31 staining in the treated groups. siRNA-mediated silencing of PHD2 increases HIF-1α and several mediators of angiogenesis. This corresponded to improved time to closure in diabetic wounds compared with sham-treated wounds. These findings suggest that impaired wound healing in diabetes can be ameliorated with therapeutic angiogenesis.

The potential of asthma adherence management to enhance asthma guidelines.

OBJECTIVE: Expert Panel Report 3 Guidelines recommend that physicians use adherence management strategies; however, the evidence for these interventions is weak. Clinicians need effective proven adherence interventions, because approximately 50% of patients with asthma do not follow physician medication recommendations, resulting in unnecessary morbidity. This review examines components of an organized adherence management program that has been successful in uncontrolled trials promoting adherence and reducing morbidity and cost. DATA SOURCES: Literature review was undertaken in the following areas of asthma management: guidelines, cost; morbidity; adherence, monitoring; and communication skills. STUDY SELECTIONS: Studies that examined outcomes from psychoeducational, behavioral, monitoring, and communication interventions. RESULTS: Studies using individual interventions by themselves were modestly effective in promoting adherence. Two uncontrolled studies of children with severe asthma, treated in both inpatient and outpatient rehabilitation settings, used 4 intervention strategies to achieve marked reduction in morbidity and cost. These strategies included: (1) objective adherence monitoring; (2) identification of the cause(s) of nonadherence; (3) delivery of specific strategies for each cause; and (4) use of motivational interviewing communication skills to enhance the delivery of the strategy. CONCLUSION: Nonadherence continues to be a significant problem. Physicians need a proven organized approach to improve adherence and reduce morbidity and cost. Evaluation of effective methods in a controlled fashion is warranted to increase adherence management evidence for future asthma guidelines.