Laser therapy for genital lichen sclerosus: A systematic review of the current evidence base.

Background: Lichen sclerosus (LS) is a chronic, inflammatory dermatosis. Initial treatment with superpotent topical corticosteroids is the accepted and evidence-based first-line therapy. For those who do not respond after exclusion of other potentiating factors, the best second-line therapy is unclear. Laser therapy is an emerging treatment for genital LS and despite uncertain efficacy its use is gaining popularity in the private sector. Objectives: We aimed to review the effectiveness of laser therapy for genital LS in men, women and children. Methods: We conducted a systematic review of all primary studies reporting the use of laser in genital LS. Ovid MEDLINE, PubMed, Ovid Embase, Cochrane CENTRAL, Web of Science, CINAHL and PsycINFO were searched from inception to February 2021. The quality of the studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials, ROBINS-I tool for non-randomized trials and Joanna Briggs Institute checklist for case studies. Results: A total of 24 studies, involving 616 adults, met inclusion criteria. These were six randomized controlled trials (RCTs), one non-randomized trial, nine single arm trials and eight case series. Where assessed, most studies suggest that laser therapy in patients with LS may improve symptoms, clinical signs, quality of life and sexual function. However, results were highly heterogeneous and methodological quality was very low, therefore meta-analysis was not possible. Conclusions: There is poor evidence to support the use of laser therapy for genital LS at present. Effectiveness of laser needs to be robustly investigated in well-conducted RCTs.

Determination of suvorexant in human plasma using 96-well liquid-liquid extraction and HPLC with tandem mass spectrometric detection.

A method, using liquid chromatography with tandem mass spectrometric detection (LC-MS/MS), was developed for the determination of suvorexant (MK-4305, Belsomra(®)), a selective dual orexin receptor antagonist for the treatment insomnia, in human plasma over the concentration range of 1-1000ng/mL. Stable isotope labeled (13)C(2)H3-suvorexant was used as an internal standard. The sample preparation procedure utilized liquid-liquid extraction, in the 96-well format, of a 100µL plasma sample with methyl t-butyl ether. The compounds were chromatographed under isocratic conditions on a Waters dC18 (50×2.1mm, 3µm) column with a mobile phase consisting of 30/70 (v/v %) 10mM ammonium formate, pH3/acetonitrile at a flow rate of 0.3mL/min. Multiple reaction monitoring of the precursor-to-product ion pairs for suvorexant (m/z 451→186) and (13)C(2)H3-suvorexant (m/z 455→190) on an Applied Biosystems API 4000 tandem mass spectrometer was used for quantitation. Intraday assay precision, assessed in six different lots of control plasma, was within 10% CV at all concentrations, while assay accuracy ranged from 95.6 to 105.0% of nominal. Quality control (QC) samples in plasma were stored at -20°C. Initial within day analysis of QCs after one freeze-thaw cycle showed accuracy within 9.5% of nominal with precision (CV) of 6.7% or less. The plasma QC samples were demonstrated to be stable for up to 25 months at -20°C. The method described has been used to support clinical studies during Phase I through III of clinical development.

Outcome measures for vulval skin conditions: a systematic review of randomized controlled trials.

Symptoms and signs of vulval skin disorders are common. These conditions can have a considerable impact on quality of life, restricting physical activities and causing difficulty in everyday activities and may also affect social, psychosexual and psychological well-being. There are no standardized measures routinely used to assess the impact of vulval disease on daily life. To report outcome measures used in clinically based randomized controlled trials (RCTs) investigating therapeutic interventions in vulval disease. The Medline, EMBASE and CENTRAL databases were searched to identify RCTs of vulval skin conditions written in English. Studies with laboratory tests or survival rates as the primary outcome, or those investigating menopausal symptoms or infections were excluded. Twenty-eight published RCTs were included. The vulval conditions represented were vulvodynia (n = 14), lichen sclerosus (n = 9), vulval intraepithelial neoplasia (n = 2), vulval pruritus (n = 2) and lichen planus (n = 1). The 28 RCTs measured 25 different outcomes, using 49 different scales. The method of outcome assessment was lacking on nine occasions. Only 21% (six of 28) of included trials had a clearly stated primary outcome. Patient-reported outcomes were more commonly reported than clinician-related outcome measures. The most commonly reported patient-rated outcome measure was a reduction in pain (measured 15 times) and an overall improvement in symptoms using a patient global assessment (measured 11 times). The most commonly reported clinician-rated outcome was an overall assessment of the appearance of affected sites (measured 13 times). There were no agreed standard scales used for the global assessments. Only nine of the recorded outcome measure tools were designed to assess vulval disease or sexual functioning, the remainder were general measures. There is heterogeneity in the outcome measures used when reporting therapeutic interventions in vulval disease. This field of dermatology would benefit from development of a vulval-specific outcome measure and the establishment of a core outcome measure set.

Diagnostic criteria for erosive lichen planus affecting the vulva: an international electronic-Delphi consensus exercise.

BACKGROUND: There is no defined set of criteria for diagnosing erosive lichen planus affecting the vulva (ELPV) and there is geographical variation in management. OBJECTIVES: To reach consensus on clinicopathological diagnostic criteria for ELPV. METHODS: This was a three-stage international electronic-Delphi exercise with a subsequent formal feedback process. In the first two rounds participants were asked to rate the importance of a list of clinicopathological criteria. Responses from round 1 were summarized and presented in round 2, along with additional criteria suggested by participants. In round 3, participants were asked to rate the items that had reached consensus as 'essential' or 'supportive' features in diagnosing ELPV. Consensus was defined as being reached if 75% of participants agreed on the importance of an item. RESULTS: A total of 73 experts representing dermatology, gynaecology, histopathology and genitourinary medicine participated; 69 (95%) completed all three rounds. Consensus was achieved for the following 'supportive' diagnostic criteria: (i) well-demarcated erosions/erythematous areas at the vaginal introitus; (ii) presence of a hyperkeratotic border to lesions and/or Wickham striae in surrounding skin; (iii) symptoms of pain/burning; (iv) scarring/loss of normal architecture; (v) presence of vaginal inflammation; (vi) involvement of other mucosal surfaces; (vii) presence of a well-defined inflammatory band involving the dermoepidermo junction; (viii) presence of an inflammatory band consisting predominantly of lymphocytes; and (ix) signs of basal layer degeneration. It was suggested that at least three supportive features should be present to make a diagnosis of ELPV, although this number is subject to further discussion. CONCLUSIONS: This study has identified a diagnostic dataset for ELPV that can be adopted into clinical practice and clinical trials.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

BACKGROUND: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K. practice against an agreed audit standard. METHODS: Criteria for standards of care for which to evaluate current service provision were set following communication with experts from the British Society for the Study of Vulval Disease. Participants from 10 U.K. centres included nine dermatologists and one gynaecologist who run specialist vulval clinics. Standards examined the documentation of disease severity/impact measures, the use of diagnostic biopsies, treatments used and assessment of treatment response. RESULTS: Audit data were collected from 172 patients. Documentation of symptoms/clinical findings was excellent (99%, 170/172). A schematic diagram was present in the notes of 87% (150/172). Patient-related disease impact measures including Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172) were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135) showed histological features consistent with erosive lichen planus. Squamous cell carcinoma developed in four patients (two vulval, two oral) and vulval intraepithelial neoplasia in two further patients. Recommended first-line treatment with a very potent topical steroid was used in 75% (129/172) with improvement in 66% (85/129). Significant variation in second-line therapy was seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of standardized guidance for treating ELPV and the need for vulval-specific outcomes. This audit should act as a framework towards improving ELPV management and to plan future research in this area.

What's new in acne? An analysis of systematic reviews and clinically significant trials published in 2010-11.

This review summarizes important clinical developments in acne treatment identified in five systematic reviews and two significant primary research studies, published between March 2010 and February 2011. Although evidence showing a direct link between development of bacterial resistance and oral antibiotic therapy for acne is not convincing, prescribers can still tailor their practice to minimize future risks by stopping treatment when appropriate, using benzoyl peroxide, and avoiding combining topical and systemic antimicrobials. A systematic review evaluating combination products containing benzoyl peroxide did not show convincing evidence that such products are superior to monotherapies. A systematic review of combined oral contraceptives confirmed their efficacy for acne in women. However, another systematic review of botanical products for acne failed to provide any good-quality evidence of benefit. A large, well-reported retrospective cohort study attempted to clarify the potential link between isotretinoin and depression/suicide. Although suicide risk peaked 6 months after isotretinoin treatment, an increased risk was present before initiation of isotretinoin, making it difficult to attribute the increased risk to isotretinoin alone. However, those with a history of suicide attempts before treatment made fewer new attempts than those whose behaviour started during treatment. This suggests that patients with severe acne with a history of attempted suicide should not automatically be refused isotretinoin. Another randomized controlled trial of 60 patients from Korea suggested that low-dose isotretinoin dose than might provide a better long-term outcome with minimal side-effects for people with moderate acne.

Positron emission tomography features of hidradenitis suppurativa.

A 35-year-old male with classical Hodgkin's lymphoma (nodular sclerosing, grade 1 histology, clinical stage 2A) underwent a positron emission tomography (PET) scan to assess response to treatment. Half body CT PET imaging was obtained using a Siemens Biograph scanner from eyes to thighs. 405 MBq of 18-fluorodeoxyglucose (FDG) was injected with acquisition starting at 60 min. There was unexpected intense focal uptake in the superficial subcutaneous tissues of the abdomen, pelvis and lateral chest wall with overlying skin thickening seen on the CT component. This was initially of concern, but the patient was known to have a history of hidradenitis suppurativa (HS). On further examination, the radiological abnormalities corresponded to the clinical sites of involvement. To the best of our knowledge, this is the first documentation of the appearance of HS on PET scan.

Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers.

TPA023, a GABA(A) alpha2,3 alphasubtype-selective partial agonist, is expected to have comparable anxiolytic efficacy as benzodiazepines with reduced sedating effects. The compound lacks efficacy at the alpha1 subtype, which is believed to mediate these effects. This study investigated the effects of 0.5 and 1.5 mg TPA023 and compared them with placebo and lorazepam 2 mg (therapeutic anxiolytic dose). Twelve healthy male volunteers participated in this placebo-controlled, double-blind, double-dummy, four-way, cross-over study. Saccadic eye movements and visual analogue scales (VAS) were used to assess the sedative properties of TPA023. The effects on posturaL stability and cognition were assessed using body sway and a standardized battery of neurophysiological memory tests. Lorazepam caused a significant reduction in saccadic peak velocity, the VAS alertness score and impairment of memory and body sway. TPA023 had significant dose dependent effects on saccadic peak velocity (85 deg/sec maximum reduction at the higher dose) that approximated the effects of lorazepam. In contrast to lorazepam, TPA023 had no detectabLe effects on saccadic latency or inaccuracy. Also unlike lorazepam, TPA023 did not affect VAS alertness, memory or body sway. These results show that the effect profile of TPA023 differs markedly from that of lorazepam, at doses that were equipotent with regard to effects on saccadic peak veLocity. Contrary to lorazepam, TPA023 caused no detectable memory impairment or postural imbalance. These differences reflect the selectivity of TPA023 for different GABA(A) receptor subtypes.

The NavChair Assistive Wheelchair Navigation System.

The NavChair Assistive Wheelchair Navigation System [19] is being developed to reduce the cognitive and physical requirements of operating a power wheelchair for people with wide ranging impairments that limit their access to powered mobility. The NavChair is based on a commercial wheelchair system with the addition of a DOS-based computer system, ultrasonic sensors, and an interface module interposed between the joystick and power module of the wheelchair. The obstacle avoidance routines used by the NavChair in conjunction with the ultrasonic sensors are modifications of methods originally used in mobile robotics research. The NavChair currently employs three operating modes: general obstacle avoidance, door passage, and automatic wall following. Results from performance testing of these three operating modes demonstrate their functionality. In additional to advancing the technology of smart wheelchairs, the NavChair has application to the development and testing of "shared control" systems where a human and machine share control of a system and the machine can automatically adapt to human behaviors.

Automatic adaptation in the NavChair Assistive Wheelchair Navigation System.

The NavChair Assistive Wheelchair Navigation System [7] is an adaptive shared control system being developed to provide mobility to those individuals who would otherwise find it difficult or impossible to use a power wheelchair due to cognitive, perceptual, or motor impairments. The NavChair provides task-specific navigation assistance to the wheelchair operator in the form of several distinct operating modes, each of which distributes control differently between the wheelchair and the operator. This paper describes the NavChair's mechanism for automatically selecting the most appropriate operating mode based on a combination of the wheelchair's immediate situation and its global location. Results from two experimental evaluations of the adaptation method are presented.