Patch Removal Research Articles

Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.

BackgroundDonepezil is an acetylcholinesterase inhibitor indicated for Alzheimer’s disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects.MethodsEach healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, or 175 mg/50 cm2. Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study.ResultsThe study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal), and mean t1/2β was ~63.77–93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%–86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period.ConclusionThe donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.

Optical Coherence Tomography in Cultivated Limbal Epithelial Stem Cell Transplantation Surgery.

Cultivated limbal epithelial stem cell transplantation (CLET) is a surgical approach reserved for severe stem cell deficiency and anterior segment pathology. The recipient cornea typically displays a highly vascularized pannus that must be dissected before graft placement. Extensive pannus dissection, however, can result in corneal thinning and increase the risk of ectasia and ultimately, of perforation. We aimed to examine the value of anterior segment optical coherence tomography (AS-OCT) intraoperatively during pannus resection and long-term postoperative follow-up of CLET surgery. This was a prospective observational case series. This study was performed on 8 eyes of 8 patients who underwent CLET surgery. Intraoperative OCT was performed before dissection and at several time points during dissection and after placement of the ex vivo cultivated graft. During the postoperative follow-up period, OCT was performed to image the graft integration and corneal thickness. Anterior segment optical coherence tomography provided high-resolution images of the corneal pannus, including the blood vessel lumen. Imaging of the pannus depth and cleavage plane was possible intraoperatively, with the patient supine. Postoperative imaging displayed the transplanted graft, temporary amniotic membrane patch, and overlying bandage contact lens. The grafts were also visible after removal of the temporary membrane patch. Four months postoperatively, the grafts were integrated into the cornea, and all 8 participants showed the presence of an epithelial layer. During CLET surgery, AS-OCT offers a noncontact method for rapid, intraoperative scanning and pachymetry mapping. Intraoperative OCT guidance assists in the removal of the delicate fibrovascular pannus. Sparing the viable corneal stroma can reduce the risk of extreme thinning, iatrogenic ectasia, and wound dehiscence while providing a smooth recipient surface for the composite graft.

Application of Geoinformatics for Assessment of Tropical Deforestation, Slash-and-Burn Land and their Impact on Climate Change in Garo Hills, Northeast India

Application of Geoinformatics for Assessment of Tropical Deforestation, Slash-and- Burn Land and their Impact on Climate Change in Garo Hills, Northeast India Tree felling in tropical forests is done for the purpose of slashand- burn agriculture after which a forest may revive back to its natural condition or may lead to degraded land. The present study was carried out to assess the deforestation rates due to slashand- burn agriculture using temporal remote sensing data. The design framework is motivated by spatial analysis of deforestation and slash-and-burn driven by indiscriminate tropical forest patch removal. In the current study it is revealed that the area under slash-and-burn increased by many folds during the last two decades (0.83% in 1991 and 5.15% in 2010). During the decades again a large chunk of forests estimated about 2,585 sq km were lost due to burning of biomass for shifting cultivation. The rate of forest degradation in all the three districts of Garo hills are identical in both the decades, but due to the efforts made by agencies there was gain of forest areas in one of the Garo hills districts in the later decade. There is no doubt about the increase of CO2 and other greenhouse gases due to burning of the tropical biomass in the Garo hills region of India. There are plenty of scopes left for undertaking scientific research in this field.

Connectivity conservation priorities for individual patches evaluated in the present landscape: how durable and effective are they in the long term?

One of the most widespread approaches for setting spatially‐explicit priorities for connectivity conservation consists in evaluating the effects of the individual removal of each habitat patch (one at a time) from the landscape. It however remains unknown the degree to which such priorities are valid and reliable in the longer term, as subsequent habitat losses and other disruptions accumulate in the landscape. We compared the patch prioritizations and estimated connectivity losses resulting from individual patch removals and from a more exhaustive assessment accounting for the potentially synergistic impacts of multiple habitat losses by testing all possible combinations of patch removals. Habitat availability (reachability) metrics and metapopulation capacity were calculated in purposefully simulated landscapes and in habitat distribution data for three bird species (NE Spain). We found that 1) individual patch removals allowed identifying areas of low contribution to connectivity that remained so after subsequent network modifications, 2) the most important patches identified through individual removals often did not coincide with those patches whose removal would actually be most detrimental after multiple habitat losses. However, these differences were smaller for the habitat reachability metrics, as well as for very mobile species that were largely insensitive to habitat spatial arrangement. If many patch losses over time are likely, it might be a more robust and fruitful conservation strategy for managers to pinpoint those patches that, with a low negative impact on connectivity, can be converted to other land uses, instead of trying to elucidate through individual patch removals which subset of protected patches would be the most effective for conserving as much connectivity as possible in the long term. Individual patch removals provide useful but non‐permanent guidelines that may need to be reassessed when substantial landscape modifications occur, which requires dynamic strategies for connectivity conservation in the face of global change.

On the almost-complete contact of elastic rough surfaces: The removal of tensile patches

The “almost-complete” contact of elastic rough surfaces is studied by the method introduced by Johnson of reducing the mean pressure below the value needed for full contact, and then removing the resulting patches of tensile stresses by superposition (Johnson et al., 1985). The procedure is examined for circular tensile patches using Sneddon’s (1946) equations, applied to a variety of (tensile) pressure distributions: Sneddon’s analysis is extended slightly to find the associated pressure distributions. It is found that the removal of circular patches of tensile stress does not alter the total load. The total out-of-contact area is always greater than the total area of tensile stress, but the increase depends on the behaviour of the pressures adjacent to the tensile region, and area increases of any amount from 14% upwards can be obtained with plausible pressure distributions: the hope that the increase will always be close to 50% is unwarranted.

Dermatopharmacokinetic bioequivalence study of two types of topical patches containing loxoprofen sodium.

This study evaluated the bioequivalence of two types of topical loxoprofen patches, LX-A and LX-P, in healthy Chinese volunteers through a dermatopharmacokinetic approach. Based on a pilot study, this study was designed as an open-label, self-controlled trial in 20 males. Subjects received application of two 3.2 x 3.2 cm(2) pieces of LX-A and LX-P patches on their backs at randomly assigned positions simultaneously. Stratum corneum (SC) samples were taken with adhesive stripping tapes prior to patch application and at 20 hours and 24 hours postdose following removal of each loxoprofen patch, respectively. Bioassay was performed with a validated high performance liquid chromatography-tandem mass spectrometry method. Bioequivalence was evaluated through a power model on the total amount of loxoprofen at each post-application point and on the percentage change of SC loxoprofen content between the two time-points. Mean (± standard deviation) total amount of SC-sampled loxoprofen was similar between LX-A and LX-P at 20 hours (38,722 ± 7,171 ng vs. 39,309 ± 9,688 ng) and 24 hours (36,638 ± 8,149 ng vs. 37,426 ± 9,029 ng) post-administration. The corresponding point estimate (90% confidence interval, 90%CI) of LX-P to LX-A was 1.00 (0.92, 1.09) and 1.02 (0.93, 1.12), respectively. In addition, the 24 hour/20 hour ratio for SC content of loxoprofen was statistically comparable between LX-A and LX-P, with both the point estimate and the 90% CI falling into the range of (0.80, 1.25). Our study indicated that LX-P and LX-A are two bioequivalent topical formulations of loxoprofen.

Abdominal Closure in Oversized Pediatric Liver Transplantation - Description and Analysis of a Technique With Step Wise Reduced Patch.

Introduction Based on a lack of size matched donors most children undergoing liver transplantation (LTX) receive a technical variant graft from adult donors, resulting in a large-for-size situation especially in smaller children. To avoid complications of further graft reduction (e.g. monosegmental LTX) or complications of an oversized liver graft (e.g. reduced graft perfusion, elevated intraabdominal pressure) we use an interim mesh. Here we describe our technique of step wise abdominal closure by a silastic mesh. Methods Retrospective analysis of our prospective LTX database with review of all surgical reports from 2003 - 2012. Transplantations were divided based on primary abdominal closure versus usage of a silastic mesh. Results Overall 298 pediatric LTX were performed, thereof 23 LTX were excluded from the study (1 intraoperative death; 22 combined liver-kidney transplantations). Primary closure was possible after 187/275(68%) LTX, whereas after 88/275(32%) LTX closure was performed using a patch. Decision about usage and size oft the patch (size trimmed) was guided by doppler ultrasound (DU) (single investigator; DU after reperfusion and abdominal closure, guided by systolic peak flow, resistance index, maximum portal flow). DU-guided operative reduction of the patch was performed every 3 to 4 days. Successful patch removal with definitive closure could be achieved in all children after a median of 2 revisions (range 1-14), after median 6 days (range 1-67 days) with no abdominal hernia development long-term (median follow-up 89mo). Children with patch were significantly younger 0.7(0-14.9) versus 2.8(0-15.9)years and lighter 7(2-35) versus 12(3-62)kg and had higher GRWR 4.4(1-12.5) versus 2.8(0.7-12)% compared to children with primary closure(all p<0.001). Comparing donor age, weight, height, graft weight or kind of graft there was no significant difference. There was no significant difference in the graft (1-/5-y 78.3/71.5% versus 86.2/68.4%) or patient survival (1-/5-y 94.6/90.5% versus 95.1/90%) between children with or without patch (p=0.449/1). Conclusion Successful abdominal closure in pediatric LTX using a silastic mesh with step-wise reduction could be achieved without further graft modifying surgery even in children with very large-for-size grafts.

Optical imaging of disrupted functional connectivity following ischemic stroke in mice

Recent human neuroimaging studies indicate that spontaneous fluctuations in neural activity, as measured by functional connectivity magnetic resonance imaging (fcMRI), are significantly affected following stroke. Disrupted functional connectivity is associated with behavioral deficits and has been linked to long-term recovery potential. FcMRI studies of stroke in rats have generally produced similar findings, although subacute cortical reorganization following focal ischemia appears to be more rapid than in humans. Similar studies in mice have not been published, most likely because fMRI in the small mouse brain is technically challenging. Extending functional connectivity methods to mouse models of stroke could provide a valuable tool for understanding the link between molecular mechanisms of stroke repair and human fcMRI findings at the system level. We applied functional connectivity optical intrinsic signal imaging (fcOIS) to mice before and 72h after transient middle cerebral artery occlusion (tMCAO) to examine how graded ischemic injury affects the relationship between functional connectivity and infarct volume, stimulus-induced response, and behavior. Regional changes in functional connectivity within the MCA territory were largely proportional to infarct volume. However, subcortical damage affected functional connectivity in the somatosensory cortex as much as larger infarcts of cortex and subcortex. The extent of injury correlated with cortical activations following electrical stimulation of the affected forelimb and with functional connectivity in the somatosensory cortex. Regional homotopic functional connectivity in motor cortex correlated with behavioral deficits measured using an adhesive patch removal test. Spontaneous hemodynamic activity within the infarct exhibited altered temporal and spectral features in comparison to intact tissue; failing to account for these regional differences significantly affected apparent post-stroke functional connectivity measures. Thus, several results were strongly dependent on how the resting-state data were processed. Specifically, global signal regression alone resulted in apparently distorted functional connectivity measures in the intact hemisphere. These distortions were corrected by regressing out multiple sources of variance, as performed in human fcMRI. We conclude that fcOIS provides a sensitive imaging modality in the murine stroke model; however, it is necessary to properly account for altered hemodynamics in injured brain to obtain accurate measures of functional connectivity.

Hydrogel-Forming Microneedles Increase in Volume During Swelling in Skin, but Skin Barrier Function Recovery is Unaffected

We describe, for the first time, quantification of in-skin swelling and fluid uptake by hydrogel-forming microneedle (MN) arrays and skin barrier recovery in human volunteers. Such MN arrays, prepared from aqueous blends of hydrolyzed poly(methylvinylether/maleic anhydride) (15%, w/w) and the cross-linker poly(ethyleneglycol) 10,000 Da (7.5%, w/w), were inserted into the skin of human volunteers (n = 15) to depths of approximately 300 μm by gentle hand pressure. The MN arrays swelled in skin, taking up skin interstitial fluid, such that their mass had increased by approximately 30% after 6 h in skin. Importantly, however, skin barrier function recovered within 24 h after MN removal, regardless of how long the MN had been in skin or how much their volume had increased with swelling. Further research on closure of MN-induced micropores is required because transepidermal water loss measurements suggested micropore closure, whereas optical coherence tomography indicated that MN-induced micropores had not closed over, even 24 h after MN had been removed. There were no complaints of skin reactions, adverse events, or strong views against MN use by any of the volunteers. Only some minor erythema was noted after patch removal, although this always resolved within 48 h, and no adverse events were present on follow-up.

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: A multicentre, randomized, assessor‐blinded study

BackgroundApplication of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming.MethodsWe conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment.ResultsOverall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and −1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms.ConclusionsCapsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment.What's already known about this topic?Application of topical capsaicin, a treatment for peripheral neuropathic pain conditions associated with allodynia, can cause painful discomfort.Therefore, a 60-min application of local anaesthetic cream before capsaicin 8% patch treatment was originally recommended.What does this study add?Oral analgesic pretreatment may reduce overall capsaicin patch treatment time and potential unpleasantness associated with applying a topical agent to an allodynic area.Based on LIFT data showing similar tolerability to capsaicin patch regardless of pretreatment method, the European Medicines Agency has issued a type II variation stating: treatment area may be pretreated with a topical anaesthetic or an oral analgesic may be given prior to patch application.

AN AUDIT OF REPORTED OPIATE ERRORS IN NORTHUMBRIA HEALTHCARE TRUST, 2012

BackgroundOpiates are frequently identified in medication incidents resulting in severe harm or death. The National Patient Safety Agency (NPSA) collects data pertaining to this and has made relevant recommendations.AimsTo identify...

Transdermal Therapy for Attention-Deficit Hyperactivity Disorder with the Methylphenidate Patch (MTS)

Transdermal technology is currently approved in the US for the administration of more than 20 medications. This current review describes the clinical research pertaining to the use of a methylphenidate patch in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents. PubMed searches were conducted using the search term ‘methylphenidate transdermal system’, and were limited to clinical trials. No limits were set for dates of publication. A total of 21 citations were identified. Studies evaluating the safety and efficacy of the methylphenidate transdermal system (MTS) in children and adolescents were included in this review. Additional studies were identified from bibliographies and the ‘Related Citations’ section of PubMed searches. The MTS delivers a range of methylphenidate doses using a drug-in-adhesive matrix patch. According to current labeling, the patch should be applied to the hip once daily for a maximum of 9 h. Serum methylphenidate levels increase over wear time, with mean time to maximum concentration (t max) reached between 8 and 10 h for a 9-h wear time, and the elimination half-life for methylphenidate is 3–4 h after patch removal. In clinical trials, ADHD symptoms were measured using the ADHD Rating Scale, Version IV, and several parent-, teacher-, and patient-rated scales. Treatment effects show statistically significant differences from baseline symptom scores starting at the first evaluation, 2 h after the patch is applied, with significant benefit lasting up to 12 h with a 9-h wear time. Adverse events with the MTS are similar to those seen with other formulations of methylphenidate, with the exception of skin-related reactions at the site of application, which were generally mild to moderate in severity. The incidence of contact allergic dermatitis with MTS is <1 %. Statistically significant improvements in health-related quality of life and medication satisfaction were also observed with the MTS compared with placebo, and after switching from oral extended-release (ER) methylphenidate. Transdermal drug delivery is an effective and safe means of administering methylphenidate for patients with ADHD.

Treatment of Weight Regain Following Roux-en-Y Gastric Bypass: Revision of Pouch, Creation of New Gastrojejunostomy and Placement of Proximal Pericardial Patch Ring

In the literature, weight regain or failure of weight loss has been reported in up to 35% of patients after Roux-en-Y gastric bypass (RYGB). Several revisional procedures have been suggested to reinitiate further weight loss in this group of patients, and placing a silastic ring around the pouch proximal to the gastrojejunostomy is one among those procedures. The aim of our study is to evaluate and compare the safety and efficacy of salvage banding using a pericardial patch after RYGB for further weight loss. Between December 2009 and April 2013, a total of 46 patients underwent revision with pericardial patch ring after RYGB for weight regain/failure of weight loss. A retrospective review of a prospectively collected database was performed, noting the outcomes and complications of the procedure. The mean body mass index at the time of revision was 40.1 ± 6.8 kg/m2. Mean percentage of excess weight loss was 23.4 ± 15.7%, 39.0 ± 27.4%, and 18.9 ± 20.5% at 6, 12 and 24 months after revision, respectively. Eight (17.4%) patients required a total of 11 readmissions due to nausea, vomiting, dysphagia and abdominal pain. Six (13.0%) patients underwent a total of six reoperations, including four patients with laparoscopic removal of the pericardial patch and another revision of RYGB, and two patients with repair of perforated ulcers. Revision with pericardial patch ring after gastric bypass for weight regain or failure of weight loss may not be feasible, safe and effective.

Flow regimes in the emptying of pipes filled with a Herschel–Bulkley fluid

The emptying of pipework from fluids of high viscosity is a significant multiphase flow problem in many food and personal care industries. Maximising product recovery whilst minimising cleaning time and effluent volume is important in minimising the environmental footprint of the plant. The cleaning of pipework fully filled by toothpaste by water under different process conditions has been studied and monitored by weighing pipes at intervals. Three flow regimes have been identified; a short core removal stage of product recovery, before water breaks through the filled pipe, and two in subsequent cleaning, film removal when there is a continuous wavy annular film on the wall, and patch removal in which the material is present as patches on the wall. The amount of product recovered in core removal is here not a function of flow conditions; however, conditions during core removal significantly affect the overall cleaning time. Overall cleaning time can be reduced by at least 25% by selecting the best removal conditions in the different stages. It is hypothesised that this is due to changes in the wall layer induced during core removal, with a very wavy wall layer leading to rapid subsequent removal. If this effect could be understood and scaled up it may be possible to improve commercial cleaning processes.

Nipple Eczema: A Diagnostic Challenge of Allergic Contact Dermatitis

Dear Editor: Nipple eczema, considered mostly as a minor manifestation of atopic dermatitis, may have unknown causes. However, its clinical course and pattern often make it difficult to differentiate its underlying causes such as irritation or sensitization. Nevertheless, allergic contact dermatitis must be considered an important cause of nipple eczema. In the present study, we analyzed the patch test results from pateints of nipple eczema by using the Korean standard series comprising 25 antigens (Chemotechnique Diagnostics, Malmo, Sweden). Antigens were carefully added into an IQ Ultra chamber® (Chemotechnique Diagnostics) which is made of additive-free polyethylene plastic foam with a filter paper incorporated, and stuck to the backs of the patients. Results were recorded 30 minutes after patch removal (as usual), and the patients were re-evaluated 48 hours later. On the basis of the recommendations of the International Contact Dermatitis Research Group, a reading of +1 (patients with erythematous papules and edema but without any vesicles) or higher was deemed a positive response. Among a total of 12 patients (all women) who were patch tested, 5 were clearly diagnosed with atopic dermatitis on the basis of their medical history and physical examination results. Nine patients showed a positive response to more than 1 antigen. Of 5 patients with a history of atopic dermatitis, 4 patients (80%) showed a positive response. Antigens with a high frequency of positive responses were, in decreasing order of frequency, Cl+Me-isothiazolinone, cobalt chloride, thimerosal, nickel sulfate, and 4-tert-butylphenol-formaldehyde resin (Table 1). Table 1 Patch test results for 12 patients with nipple eczema Of 9 patients who had positive patch test responses, 7 (77.78%) had a bilateral distribution of lesions, and 8 patients (88.89%) showed spreading of lesions over the periareolar skin. With respect to the progression of eczema, 8 patients (88.89%) had acute lesions. However, 3 patients with negative patch test responses showed only unilateral lesions, which were restricted to the nipple and areola rather than the periareolar skin. Thus, there was a significant difference with respect to the involved area and distribution of the lesions (p<0.05) (Table 2). Table 2 Clinical characteristics of nipple eczema according to distribution of lesion and history where the positive patch test reaction indicated allergic contact dermatitis Nine patients with a positive patch test were advised to avoid the use of products containing the positive antigens, after which 5 patients (56%) showed reduced recurrence of nipple eczema. Nipple eczema is a characteristic minor dermatologic finding indicating atopic dermatitis1. Nevertheless, cases in which nipple eczema was not a characteristic finding of atopic dermatitis have been reported2,3. If nipple eczema does not improve after conventional treatment for atopic dermatitis, or if active symptoms of eczema such as severe erythema and exudation are limited to areas that are frequently affected by atopic dermatitis, allergic contact dermatitis should always be considered first. In this study, positive patch tests to ≥1 antigens were found in 9 of 12 patients (75%). According to an epidemiological survey by the Korean Contact Dermatitis Research Group, Cl+Me-isothiazolinone is not considered a frequent antigen; however, in the present study, this antigen provoked positive responses as frequently as metal ions did. Cl+Me-isothiazolinone is commonly found in preservatives, deterge nts, and fabric softeners; therefore, traceable amounts remaining in undergarments after washing or in personal-care products may act as antigens. Both repeated contact, even at the subclinical threshold, and a weak barrier function in skin affected by atopic dermatitis can contribute to the development of contact sensitization. To prevent chronic recurrent contact dermatitis, the causative antigens should be identified by screening with patch test series, and an avoidance-learning program should be followed4. We found considerable clinical improvements and reduced recurrence in 5 of the 9 patients who had positive patch tests and followed an avoidance-learning program. In conclusion, allergic contact dermatitis should be considered first in the differential diagnosis of nipple eczema, especially in patients showing bilateral lesions and lesions extending into the periareolar skin.

Treatment of Neuropathic Pain with the Capsaicin 8% Patch: Is Pretreatment with Lidocaine Necessary?

The capsaicin 8% patch can effectively treat neuropathic pain, but application can cause discomfort or a burning sensation. Until March 2013, it was recommended that patients be pretreated with a topical anesthetic, for example lidocaine, before capsaicin patch application. However, speculation existed over the need for pretreatment and its effectiveness in alleviating treatment-associated discomfort. This article compares tolerability to and efficacy of the capsaicin patch in pretreated and non-pretreated patients. All patients received a single capsaicin patch application. Pretreated patients received a lidocaine plaster before and intravenous lidocaine and metamizole infusions during capsaicin patch application. Pain levels, assessed using a Numeric Rating Scale (NRS), were used to determine tolerability and efficacy. All patients (pretreated n = 32; non-pretreated n = 26) completed 100% of the intended capsaicin patch application duration. At the time of capsaicin patch removal, 69% of pretreated and 88% of non-pretreated patients reported an NRS score increase, which returned to baseline by 6 hours post-treatment. There was no significant difference in mean NRS score between patient groups at any time during or after capsaicin patch treatment. Response was similar between patient groups; capsaicin patch treatment provided rapid and significant pain reductions that were sustained over 12 weeks. The same proportion of pretreated and non-pretreated patients reported willingness to receive retreatment with the capsaicin patch. This analysis shows that the capsaicin 8% patch is generally tolerable, and the small discomfort associated with patch application is short-lived. Lidocaine pretreatment does not have a significant effect on tolerability, efficacy, or patient willingness to receive retreatment.

Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor

Natural moisturizing factor (NMF) serves as the primary humectant of the stratum corneum (SC), principally comprised of hygroscopic amino acids and derivatives that absorb moisture. Barrier disruption has been shown to differentially affect the levels of specific NMF components, though the kinetics of NMF component restoration following disruption have not been examined. Here, we investigated the impact of barrier disruption caused by surfactant exposure on a subset of NMF components immediately following exposure and out to 10days post-exposure. Volunteers wore patches containing either 1% w/v sodium lauryl sulphate (SLS) or distilled water on their forearms for 24h. Measurements of transepidermal water loss, erythema, SC water content and a subset of SC NMF and lipid components were obtained at both sites before treatment, the day of patch removal, and 1, 2, 3, 6, and 10days following treatment. Most measured NMF components decreased in response to SLS exposure. Exceptions were increases in lactate, ornithine and urea, and no difference in proline levels. In the days following exposure, reduced levels of several NMF components continued at the SLS site; however, all measured NMF components demonstrated equivalence to the vehicle control within 10days. Histidine pH 7, lactate, ornithine and urea were the first to achieve levels equivalent to the vehicle control site, normalizing within 1day after patch removal. Results imply that NMF components derived from sweat and urea cycling are least impacted by SLS exposure whereas NMF components derived from degradation of filaggrin and/or other S-100 proteins are most impacted. This implies the restoration of the processes responsible for S-100 protein processing into free amino acids takes several days to return to normal. Further examination of the enzymes involved in S-100 protein processing following barrier disruption would provide insight into the pathway(s) for NMF restoration during SC recovery.

Primary irritation index and safety zone of cosmetics: retrospective analysis of skin patch tests in 7440Korean women during 12 years

Cosmetics are products used over long periods by the public, and their safety is very important. Several types of human tests are used widely for the evaluation of cosmetics including single patch tests, in-use tests, human repeated insult patch test (HRIPT). However, there is no clear and well-defined published objective and standardized criteria for primary skin irritation in regard to the large variety of cosmetic products. This study analysed human patch tests conducted from May 2001 to December 2012 with 4606 materials of prototype or finished cosmetic products on 7440 normal Korean women aged 18-60years. The tested products were patched under occlusion for 24 or 48h, and skin tolerance was assessed twice at 30min and 24h after patch removal using a 5-step scale according to the CTFA guidelines. Human patch tests for cosmetics were performed of 4606 cases, and 30-33 subjects participated in each case. The response in each case was calculated based on total subject number, skin reaction intensity and the number of respondents. The calculated response was standardized using the z-score, and a safety zone was provided in terms of human primary irritation in accordance with the human skin reaction evaluation criteria and usage or formula of cosmetics. This study established the safety criteria for irritation in the cosmetics field.

Native Pulmonary Valve Restoration After Remote Tetralogy of Fallot Repair

Methods to repair tetralogy of Fallot have evolved from large ventriculotomy, large transannular patch placement techniques to smaller, transatrial approaches with valve-sparing strategies in select patients. Despite these advances, there continue to be patients in whom transannular patch is inevitable, and the management of the resulting pulmonary insufficiency that develops from this has been the source of considerable discussion. Techniques aimed at restoring pulmonary valve competence utilizing the remaining valve leaflets after transannular patch placement have recently been proposed for very select patient populations. We review the technical aspects of the operation including removal of the transannular patch and bicuspidization of a formerly tricuspid pulmonary valve, which results in a competent, nonstenotic valve. This report confirms the feasibility of these operative details and highlights the importance of planning before initial repair of tetralogy of Fallot as a way to prepare for a future valve restoration procedure and therefore avoid prosthetic valve placement.

Bacterial cellulose membranes as drug delivery systems: An in vivo skin compatibility study

Bacterial cellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane by several bacteria that demonstrated to be able to modulate the skin release of model drugs. In the present study, the skin irritation potential of BC was evaluated in human subjects. BC membranes with and without glycerin (acting as plasticizer) were tested. No significant differences were observed for transepidermal water loss (TEWL) measurements in comparison with negative control, 2 and 24h after patch removal, which is an indicator of an absence of barrier disruption. Similar results were found for erythema. Clinical scores were zero at both times for all volunteers, with the exception of five volunteers that exhibited weak reactions. BC with glycerin provided a skin moisturizing effect statistically higher than the negative control (p=0.044), which was not observed for BC alone. The good skin tolerance found after a single application under occlusion reinforces the putative interest of BC membranes as supports for drug topical delivery. Besides modifying the mechanical properties, the inclusion of glycerin results in a skin moisturizing effect which could be clinically relevant for the treatment for skin diseases characterized by dryness, such as psoriasis and atopic dermatitis.