Anxiety and depressive symptoms and migraine-related outcomes in children and adolescents.

OBJECTIVE: The objective of this study was to explore the longitudinal relationship between anxiety and depressive symptoms and migraine outcomes in children and adolescents. BACKGROUND: Children and adolescents with migraine experience more anxiety and depressive symptoms than their peers without migraine, but it is unknown if these symptoms are associated with differential migraine outcomes. METHODS: In this prospective clinical cohort study, children and adolescents aged 8.0-18.0 years with migraine completed headache questionnaires and validated measures of anxiety and depressive symptoms (Patient-Reported Outcomes Measurement Information System) at an initial consultation and at their first follow-up visit with a neurologist. Changes in monthly headache frequency and changes in migraine-related disability (Pediatric Migraine Disability Assessment) were tracked at each time point. The relationships between these migraine outcomes and anxiety and depressive symptoms were estimated using models controlling for sex, age, headache frequency, and treatment type. RESULTS: There were 123 consenting participants. In models adjusted for age, sex, baseline disability score, and treatment type, baseline anxiety and depressive symptom levels were not significantly associated with change in headache frequency (for anxiety symptoms: ß = -0.05, 95% confidence interval [CI] = -0.268 to 0.166, p = 0.639; for depressive symptoms: ß = 0.14, 95% CI = -0.079 to 0.359, p = 0.209). Similarly, in models adjusted for age, sex, baseline headache frequency, and treatment type, the change in disability was not associated with baseline anxiety (ß = -0.45, 95% CI = -1.69 to 0.78, p = 0.470), nor with baseline depressive symptom scores (ß = 0.16, 95% CI = -1.07 to 1.40, p = 0.796). In post hoc exploratory analyses (N = 84 with anxiety and N = 82 with depressive symptom data at both visits), there were also no significant associations between change in mental health symptoms and change in headache frequency (for anxiety symptoms: ß = -0.084, 95% CI = -0.246 to 0.078, p = 0.306; for depressive symptoms: ß = -0.013, 95% CI = -0.164 to 0.138, p = 0.865). Similarly, the change in disability scores between visits was not related to the change in anxiety (ß = 0.85, 95% CI = -0.095 to 1.78, p = 0.077) nor depressive symptom scores (ß = 0.32, 95% CI = -0.51 to 1.15, p = 0.446). CONCLUSION: Baseline anxiety and depressive symptom levels were not associated with longitudinal migraine outcomes and neither were longitudinal changes in anxiety and depressive symptom levels; this contradicts popular clinical belief that mental health symptoms predict or consistently change in tandem with migraine outcomes.

A Diagnostic-Driven Prospective Clinical Study Evaluating the Combination of an Antibiofilm Agent and Negative Pressure Wound Therapy.

BACKGROUND: Each year, millions of Americans develop truncal pressure ulcers (PUs) which can persist for months, years, or until the end of life. Despite the negative impact on quality of life and escalating costs associated with PUs, there is sparse evidence supporting validated and efficacious treatment options. As a result, treatment is based on opinion and extrapolation from other wound etiologies. The ideal reconstructive plan maximizes the patient's nutritional status, incorporates the basic tenets of wound bed preparation (debridement, offloading, proper moisture balance, reduction of bacterial burden), and employs diagnostics to guide therapeutic intervention. The use of combination therapies can potentially overcome several of the barriers to wound healing. Negative pressure wound therapy (NPWT), a commonly used modality in the management of PUs, facilitates healing by stimulating the formation of granulation tissue and promoting wound contraction; however, NPWT alone is not always effective. Clinical studies examining microbial bioburden in PUs determined that most ulcers contain bacteria at levels that impede wound healing (>104 CFU/g). OBJECTIVE: Thus, we hypothesized that adding an anti-microbial agent to decrease both planktonic and biofilm bacteria in the wound would increase the efficacy of NPWT. METHOD: In this prospective study, twenty patients with recalcitrant PUs that previously failed NPWT were treated with a biofilm-disrupting agent (Blast-X, Next Science, Jacksonville, FL, USA) in combination with NPWT. Fluorescence imaging was used to follow bacterial burden and guide therapy. RESULTS: In total, 45% of the PUs reduced in size over the course of the four-week study, with a resolution of bacterial fluorescence in the NPWT dressing and wound bed seen in an average of three weeks. CONCLUSION: The combination of an antibiofilm agent and NPWT reduced bacterial levels and improved wound healing in recalcitrant PUs.

A double-blind trial comparing an antimicrobial combination to standard care in hard-to-heal wounds.

OBJECTIVE: Excessive numbers of bacteria in hard-to-heal wounds impede wound healing. Numerous topical antiseptics have demonstrated effectiveness in benchtop studies; however, few clinical studies have demonstrated efficacy in the target population: patients with hard-to-heal wounds. This study addressed the clinical efficacy of a novel antibiofilm cleanser and gel in reducing bacterial load and improving wound outcomes. METHOD: Hard-to-heal wounds were photographed, measured and evaluated for bacterial load using fluorescence imaging weekly for four weeks. The target ulcers were randomised to be cleaned and treated with either a synergistic antibiofilm cleanser and antibiofilm gel with standard of care (AMC-AMG + SoC) or normal saline wash and an amorphous gel with standard of care (NSS-HG + SoC). RESULTS: A Chi-squared test of independence determined that the relationship between the treatment and the patient reaching 40% percentage area reduction (PAR) in four weeks was not significant (χ2(1, n=54)=0.73; p=0.39 at a significance level of 0.05); however, there was a strong trend favouring the antibiofilm cleanser and gel. A significant reduction (p<0.05) in bacterial load was observed in the antibiofilm group. CONCLUSION: This randomised controlled double-blind proof-of-concept study suggests that the performance of antibiofilm agents in vivo is comparable to that in vitro studies.

A prospective clinical pilot study comparing two post-operative dressings in the treatment of surgical incisions in volunteers.

OBJECTIVE: Surgical site infections (SSIs) are one of the leading causes of post-operative morbidity and mortality worldwide. The original post-operative dressing, gauze taped in place, did not protect the incision from contamination. A recent clinical trial demonstrated that transparent films were superior to gauze in reducing SSIs. Transparent films are semi-occlusive (semi-permeable, transparent). They protect the incision from contamination; however, one of the drawbacks of current films is that they may become dislodged during daily activities, such as showering. Patients may not realise that the integrity of the dressing has been compromised, leading to soiling of the incision and possible infection. DrySee (DrySee Inc., US) is a novel film dressing with a colorimetric indicator that alerts the patient when the dressing has been compromised. METHOD: This trial compared the film dressing with the indicator (DSD) to a commonly used post-operative dressing comparator (Tegaderm + Pad; 3M, US). A 1.5cm incision was made in the volar forearm of volunteers. The incisions were randomly treated with the DSD or comparator dressing. RESULTS: A cohort of 20 volunteer patients was recruited. The DSD had a greater wear time and patients reported that the DSD dressing stayed in place better during activities compared to the comparator. CONCLUSION: Overall, 75% of patients preferred DSD and 25% preferred the comparator.

The efficacy of sodium hypochlorite antiseptic: a double-blind, randomised controlled pilot study.

OBJECTIVE: According to a recent clinical trial, 82% of hard-to-heal wounds harbour levels of bacteria that impede healing. A follow-up analysis of trial data revealed that the use of antiseptic cleansers did not correlate with bacterial burden. At a minimum, these findings suggest the need for clinical research into the efficacy of antiseptics in reducing bacterial burden. Evidence supporting the bacterial killing ability of antiseptics is largely derived from preclinical and laboratory studies. Few clinical trials have examined bacterial levels and healing rates in hard-to-heal wounds. Fortunately, the advent of fluorescence imaging to detect bacterial burden has simplified the conduct of clinical research examining the effectiveness of antiseptics in the clinic setting. The aim of this study was to evaluate the efficacy of a modified sodium hypochlorite (NaOCl) solution in reducing wound size and bacterial load in hard-to-heal wounds. METHOD: In this randomised, double-blind pilot study, patients were randomised to one of two groups: daily wound cleansing with either normal saline solution (NSS) or NaOCl. Patients and investigators were blinded to the allocation. All wound types were included. RESULTS: A total of 16 patients consented to participate. At the initial visit, the target ulcer was measured and a fluorescence image to evaluate bacterial load obtained. The wound was then cleansed with either NSS or NaOCl and fluorescence imaging repeated. Patients cleansed the wound daily in accordance with the randomisation schedule. They returned to the clinic weekly for four weeks, and on each visit the wound was measured and a fluorescence image captured. Patients receiving NaOCl had a greater percent reduction in wound area versus NSS; although the first phase of the study was not powered for statistical significance, there was a strong trend favouring NaOCl. In addition, there was greater bacterial reduction in the NaOCl group. CONCLUSION: Based on the results of this pilot study, enrolment has continued in order to increase the study's power. This pilot study suggests that sodium hypochlorite is efficacious in reducing bacterial burden and promoting healing.

Uncovering the high prevalence of bacterial burden in surgical site wounds with point-of-care fluorescence imaging.

Detection of bacterial burden within or near surgical wounds is critical to reducing the occurrence of surgical site infection (SSI). A distinct lack of reliable methods to identify postoperative bioburden has forced reliance on clinical signs and symptoms of infection (CSS). As a result, infection management has been reactive, rather than proactive. Fluorescence imaging of bacterial burden (FL) is positioned to potentially flip that paradigm. This post hoc analysis evaluated 58 imaged and biopsied surgical site wounds from the multi-centre fluorescence imaging assessment and guidance clinical trial. Diagnostic accuracy measures of CSS and FL were evaluated. A reader study investigated the impact of advanced image interpretation experience on imaging sensitivity. Forty-four of fifty-eight surgical site wounds (75.8%) had bacterial loads >104  CFU/g (median = 3.11 × 105  CFU/g); however, only 3 of 44 were CSS positive (sensitivity of 6.8%). FL improved sensitivity of bacterial detection by 5.7-fold compared with CSS alone (P = .0005). Sensitivity improved by 11.3-fold over CSS among clinicians highly experienced with FL interpretation (P < .0001). Surgical sites that reach the stage of referral to a wound specialist frequently harbour asymptomatic high bacterial loads that delay healing and increase infection risk. Advanced imaging of pathological bacterial burden improves surgical site monitoring and may reduce the rate of SSIs.

A novel debridement device for the treatment of hard-to-heal wounds: a prospective trial.

OBJECTIVE: Debridement, the removal of nonviable tissue, forms the foundation of wound care practice. Clinicians have a variety of debridement methods at their disposal: sharp, biologic, enzymatic, autolytic and mechanical. The choice of debridement technique depends on the patient care setting, ulcer type and the clinician's experience, training, comfort level and licensure. This prospective study evaluated a novel debridement instrument, EZ-Debride (MDM Ventures, US). Cutting flutes on the head of the tool permit uniform removal of dead tissue while lessening the risk of deeper injury. It may also minimise pain during the debridement procedure. METHOD: Subjects with hard-to-heal wounds, drawn from a single wound care centre, participated in this institutional review board-approved prospective clinical study. Pain was measured before, during and after debridement using a numerical scale. Assessment of bacterial burden using fluorescence imaging (MolecuLight, Canada) was performed before and after debridement. RESULTS: Enrolment of 10 male and 12 female subjects, with a total of 28 wounds, was carried out over a two-month period by two investigators at a single institution. The average age of subjects was 64 years (range: 22-95 years). The average wound duration was 29 weeks (range: 6-142 weeks). Wound types included diabetic foot, venous leg and pressure ulcers, post-surgical and traumatic wounds. The average pain score at the time of enrolment was 3.9. Subjects reported an average increase in pain with debridement of 0.6 points (range: 0-8). Fluorescence imaging demonstrated a reduction in bacterial load in 69% of cases, with complete resolution in 19% of wounds. Haemostasis was achieved with direct pressure in all cases and the only adverse event was a wound infection that occurred four days after debridement. CONCLUSION: The results suggest that this novel debridement tool can safely remove nonviable tissue with minimal discomfort and reduce bacterial burden similar to results achieved by sharp debridement.

Efficacy and safety of a porcine peritoneum-derived matrix in diabetic foot ulcer treatment: a pilot study.

OBJECTIVE: A third of people with diabetes will develop a foot ulcer during their lifetime. The absence of pain secondary to neuropathy often leads to a delay in diagnosis and treatment. Diabetic foot ulcer (DFU) complications, such as infection and amputation, increase mortality and strain the financial resources of health systems across the world. Cellular and/or tissue products (CTPs) have played an important role in the closure of DFUs. Investigators continue to search for new CTPs that facilitate healing. The aim of this study was to assess the efficacy and safety of a porcine peritoneum-derived matrix in DFU treatment. METHOD: Patients with longstanding DFUs participated in this institutional review board-approved, multicentre, prospective pilot study evaluating the time to healing over 12 weeks. In addition to weekly assessments for wound size, investigators analysed bacterial burden using the MolecuLight procedure (MLiX) and bacterial protease (BPA) testing. Participants received a weekly application of Meso Wound Matrix Scaffold (MWM), a lyophilised porcine peritoneum-derived matrix (DSM Biomedical Inc., Exton, PA, US) for up to eight weeks. Descriptive statistics were chosen for this analysis. RESULTS: A total of 12 male patients and three female patients with an average age of 57 years were enrolled over a two-month period. The average wound duration was 30 weeks. Due to unrelated health issues, four participants were withdrawn. For the study endpoint of complete wound closure at 12 weeks, six (55%) of the remaining 11 patients achieved complete closure, and four (36%) patients healed during the 8-week treatment period. The average number of CTP applications was six. Patients who healed all had negative BPA by nine weeks and no fluorescence on MLiX, indicating low bacterial load. CONCLUSION: This small pilot study indicates that patients with longstanding DFUs may respond to a porcine peritoneal-derived CTP. In this study, the CTP appears to have inhibited bacterial growth in the wound; however, further research is needed.

Evaluation of the combination of a biofilm-disrupting agent and negative pressure wound therapy: a case series.

OBJECTIVE: Approximately three million people in the US have hard-to-heal pressure ulcers (PUs), including 10% of hospitalised patients. Healing depends on ulcer stage and patient comorbidities. Despite advances in nutrition and wound care, PUs can take months or years to reach complete closure. To date, clinical studies have focused on single modality therapy. However, there is no one therapy that can address all of the deficits in these complex, hard-to-heal wounds. A commonly used treatment for PUs, negative pressure wound therapy (NPWT), has demonstrated improved healing in Stage 3 and 4 PUs. NPWT entails applying suction to a porous sponge fitted into the wound cavity and sealed with an occlusive dressing. Negative pressure facilitates wound healing by removing wound fluid containing harmful proteases, stimulating the formation of granulation tissue and promoting wound contracture. However, it does not affect biofilm formation. We hypothesised that adding an antibiofilm agent might increase the effectiveness of NPWT in recalcitrant PUs. METHOD: A prospective case series was conducted in outpatient wound care centres and a skilled nursing facility to examine the combination of a biofilm-disrupting antimicrobial agent (Blast-X, Next Science, US) in combination with NPWT (VAC, 3M, US) in healing and reducing bacterial burden in treatment-resistant pressure ulcers. Patients consented to application of the antibiofilm agent and NPWT three times per week for four weeks. The wounds were measured, imaged for bacteria and tested for host and bacterial protease activity weekly. RESULTS: Of the 10 patients, four dropped out of the study before the end of the four weeks. Of the remaining six, four patients experienced a reduction in wound surface area and volume, reduced protease activity and lower bacterial levels. CONCLUSION: The results of this study showed that multimodal therapy, including NPWT and biofilm disruption, may restart the healing of stagnant treatment-resistant PUs.

Comparing near infrared spectroscopy and transcutaneous oxygen measurement in hard-to-heal wounds: a pilot study.

OBJECTIVE: Oxygen plays an integral role in all phases of the wound healing process and tissue oxygenation is a key determinant of wound healing. A comprehensive evaluation of patients with hard-to-heal wounds must include measurement of oxygenation in and around the area of skin breakdown. The current gold standard, transcutaneous oxygen measurement (TCOM), has numerous drawbacks and as a result has fallen into disuse. METHOD: This study compared measurement of tissue oxygenation of near infrared spectroscopy (NIRS) with TCOM in patients with acute and hard-to-heal wounds. The Shapiro-Wilk test was used to evaluate the normality of the data. The level of agreement between NIRS and TCOM was determined using Bland-Altman analysis. The relationship between TCOM and NIRS was examined using Pearson correlation. RESULTS: A total of 24 observations were obtained from 10 patients using TCOM and NIRS. The weighted mean partial pressure of oxygen (pO2) in the study population was 39.54mmHg (8.96 standard deviation). Bland-Altman analysis showed that mean difference was positive (18.75), suggesting an overestimation of oxygen measurements using TCOM compared with NIRS. The oxygen levels measured by TCOM and NIRS showed a strong correlation (r=0.74). CONCLUSION: The wound and hyperbaric community would benefit from a simplified procedure for measuring tissue oxygenation. These findings suggest a strong trend toward correlation between NIRS and TCOM. A further study in a larger population is recommended. NIRS offers several advantages over TCOM. Clinicians have immediate point-of-care visualisation of tissue oxygenation using a handheld device. The procedure takes minutes to perform and is less operator-dependent than TCOM. Finally, NIRS allows measurement of oxygenation in the wound bed, while TCOM does not.

Family Perspectives on Visiting the Pediatric Emergency Department for Migraine: A Qualitative Study.

OBJECTIVE: The aim of this study was to explore the perspectives of families regarding their expectations and experience of visiting the emergency department (ED) for migraine. METHODS: This was a qualitative study involving the families of 25 patients aged 10 to 18 years receiving ED care for acute migraine. Following their visit, independent semistructured telephone interviews were conducted with both the patient and parent or guardian. Questions were designed to explore factors pertaining to the family's perspective regarding their visit to the ED and expectations for the ED visit. RESULTS: Families reported a variety of reasons for visiting the ED. The majority of participants reported that they were worried about their headaches. Families more commonly had expectations for treatment than they did for investigations. As compared with patients, parents more commonly reported specific expectations for investigations and less commonly expressed concerns about intravenous treatments. Expectations for treatment efficacy varied: whereas some parents expected complete pain relief, for others, lesser degrees of relief were considered satisfactory. The experience of treatment efficacy was related to willingness to receive the same treatment again. CONCLUSIONS: Given that a high frequency of families endorsed that they were worried about the headache when presenting to the ED, clinicians should strive to make a diagnosis of migraine in the ED setting and to educate families about this diagnosis. Because of divergent parent and patient perspectives, health care providers should inquire about family expectations, especially in relation to expectations for investigations and concerns surrounding intravenous interventions, and ensure that both the patient's and parent's perspectives are considered when developing a management plan for pediatric migraine.

Real-time bacterial fluorescence imaging accurately identifies wounds with moderate-to-heavy bacterial burden.

OBJECTIVE: Clinical evaluation of signs and symptoms (CSS) of infection is imperative to the diagnostic process. However, patients with heavily colonised and infected wounds are often asymptomatic, leading to poor diagnostic accuracy. Point-of-care fluorescence imaging rapidly provides information on the presence and location of bacteria. This clinical trial (#NCT03540004) aimed to evaluate diagnostic accuracy when bacterial fluorescence imaging was used in combination with CSS for identifying wounds with moderate-to-heavy bacterial loads. METHODS: Wounds were assessed by study clinicians using NERDS and STONEES CSS criteria to determine the presence or absence of moderate-to-heavy bacterial loads, after which the clinician prescribed and reported a detailed treatment plan. Only then were fluorescence images of the wound acquired, bacterial fluorescence determined to be present or absent and treatment plan adjusted if necessary. RESULTS: We examined 17 VLUs/2 DFUs. Compared with CSS alone, use of bacterial fluorescence imaging in combination with CSS significantly improved sensitivity (22% versus 72%) and accuracy (26% versus 74%) for identifying wounds with moderate-to-heavy bacterial loads (≥104 CFU/g, p=0.002). Clinicians reported added value of fluorescence images in >90% of study wounds, including identification of wounds incorrectly diagnosed by CSS (47% of study wounds) and treatment plan modifications guided by fluorescence (73% of study wounds). Modifications included image-guided cleaning, treatment selection, debridement and antimicrobial stewardship. CONCLUSION: Findings from this pilot study suggest that when used in combination with CSS, bacterial fluorescence may: (1) improve the diagnostic accuracy of identifying patients with wounds containing moderate-to-heavy bacterial loads and (2) guide more timely and appropriate treatment decisions at the point-of-care.

Novel Multivalent Wound-Healing Ointment Provides Bioburden Control and Moisture Management: A Retrospective Registry Data Analysis.

OBJECTIVE: The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds. DESIGN: Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry. SETTING: Wound clinics in the United States were asked to participate in the registry. PATIENTS: Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry. INTERVENTIONS: Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up. MAIN OUTCOME MEASURES: Physicians calculated each patient's percentage wound reduction at each visit. MAIN RESULTS: Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment. CONCLUSION: The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.