Effect of Keloid Properties on Treatment Efficacy, a Systematic Review.

BACKGROUND: The efficacy of keloid treatment in randomized studies is highly variable. However, no systematic review has been performed to evaluate the effect of different keloid properties on treatment efficacy. OBJECTIVE: To identify clinically relevant keloid properties that may influence treatment efficacy. MATERIALS AND METHODS: An electronic database search was conducted. Two reviewers independently selected randomized controlled trials (RCTs) and performed a methodologic quality assessment using the Cochrane risk-of-bias 2.0 tool. RESULTS: One thousand five hundred twenty studies were screened, and 16 RCTs, involving 1,113 patients, were included. The authors found lower efficacy in older keloids ( n = 3), keloids located on the chest, extremities, pinna, and shoulder ( n = 3), larger keloids ( n = 2), lower baseline Vancouver Scar Scale score ( n = 1), and keloids with history of recurrence ( n = 1). Overall, most studies had a high risk of bias. CONCLUSION: Only a minority of studies specifically addressed keloid properties, which makes comparisons between studies challenging. The authors' results suggest that keloid location, duration prior to treatment, size, history of recurrence, and severity are clinically relevant keloid properties that affect treatment efficacy. Further studies are crucial to corroborate the authors' findings, establish a clinically relevant keloid classification, and ultimately develop an evidence-based treatment algorithm that takes these properties into account.

Needle-free electronically-controlled jet injector treatment with bleomycin and lidocaine is effective and well-tolerated in patients with recalcitrant keloids.

OBJECTIVES: The treatment of recalcitrant keloids is challenging. Although intralesional bleomycin using conventional needle injectors (CNI) is effective, it has important drawbacks, such as the need for repetitive and painful injections. Therefore, we aimed to evaluate the effectiveness, tolerability and patient satisfaction of intralesional bleomycin with lidocaine administered with a needle-free electronically-controlled pneumatic jet-injector (EPI) in recalcitrant keloids. METHODS: This retrospective study included patients with recalcitrant keloids who had received three intralesional EPI-assisted treatments with bleomycin and lidocaine. Effectiveness was assessed using the Patient and Observer Scar Assessment Scale (POSAS) at baseline and four to six weeks after the third treatment. Additionally, treatment related pain scores numeric rating scale, adverse effects, patient satisfaction and Global Aesthetic Improvement Scale (GAIS) were assessed. RESULTS: Fifteen patients with a total of >148 recalcitrant keloids were included. The median total POSAS physician- and patient-scores were respectively 40 and 41 at baseline, and reduced with respectively 7 and 6-points at follow-up ( p < 0.001; p < 0.001). The median pain scores during EPI-assisted injections were significantly lower compared to CNI-assistant injections, (2.5 vs. 7.0, respectively ( p < 0.001)). Adverse effects were mild. Overall, patients were "satisfied" or "very satisfied" with the treatments (14/15, 93.3%). The GAIS was "very improved" in one patient, "improved" in nine patients and "unaltered" in four patients. CONCLUSIONS: EPI-assisted treatment with bleomycin and lidocaine is an effective, well tolerated, patient-friendly alternative for CNI in patients with recalcitrant keloid scars. Randomized controlled trials are warranted to confirm our findings and improve the clinical management of recalcitrant keloids.

Home-Use Hyaluronic Acid Jet Injectors: Unreliable and Unsafe.

BACKGROUND: Needle-free hyaluronic acid (HA) jet injectors are gaining popularity for rejuvenation treatment. The devices are widely available online and are used for self-injection or in beauty salons by nonphysicians. However, little is known about their performance and safety. OBJECTIVE: To explore the injection efficiency and cutaneous biodistribution patterns administered with home-use compared with medical jet injectors and to assess safety aspects. MATERIALS AND METHODS: The authors injected HA into ex vivo human skin with 4 home-use and 2 medical injectors. The intracutaneous dose of HA was calculated, and the cutaneous biodistribution of HA was assessed using a 3-dimensional Fluorescent Imaging Cryomicrotome System (3D-FICS). Safety aspects were evaluated based on the presence of a manual, CE (conformité européenne) mark, and sterility. RESULTS: The intracutaneous dose delivered by the home-use injectors was markedly lower compared with the medical injectors. 3D imaging for home-use injectors showed superficial epidermal distribution with low distribution volumes. For medical injectors, volumes were substantially larger and mainly middermal. All evaluated safety aspects were lacking. CONCLUSION: Results of this study suggest that the specific combinations of home-use injectors and HA used in this study are unreliable and unsafe, which casts doubts on the performance of these treatments in general.

Impact of skin hydration on patterns of microthermal injury produced by fractional CO2 laser.

OBJECTIVES: The impact of skin hydration on patterns of thermal injury produced by ablative fractional lasers (AFLs) is insufficiently examined under standardized conditions. Using skin with three different hydration levels, this study assessed the effect of hydration status on microchannel dimensions generated by a fractional CO2 laser. METHODS: A hydration model (hyperhydrated-, dehydrated- and control) was established in ex vivo porcine skin, validated by changes in surface conductance and sample mass. After, samples underwent AFL exposure using a CO2 laser (10,600 nm) at two examined pulse energies (10 and 30 mJ/mb, fixed 10% density, six repetitions per group). Histological assessment of distinct microchannels (n = 60) determined three standardized endpoints in H&E sections: (1) depth of microthermal treatment zones (MTZs), (2) depth of microscopic ablation zones (MAZs), and (3) coagulation zone (CZ) thickness. As a supplemental in vivo assessment, the same laser settings were applied to hyperhydrated- (7-h occlusion) and normohydrated forearm skin (no pretreatment) of a human volunteer. Blinded measurement of MAZ depth (n = 30) was performed using noninvasive optical coherence tomography (OCT). RESULTS: Modest differences in microchannel dimensions were shown between hyperhydrated, dehydrated and control skin at both high and low pulse energy. Compared to controls, hyperhydration led to median reductions in MTZ and MAZ depth ranging from 5% to 8% (control vs. hyperhydrated at 30 mJ/mb; 848 vs. 797 µm (p < 0.003) (MAZ); 928 vs. 856 µm (p < 0.003) (MTZ)), while 14%-16% reductions were shown in dehydrated skin (control vs. dehydrated at 30 mJ/mb; MAZ: 848 vs. 727 µm (p < 0.003); MTZ: 928 vs. 782 µm (p < 0.003)). The impact of skin hydration on CZ thickness was in contrast limited. Corresponding with ex vivo findings, hyperhydration was similarly associated with lower ablative depth in vivo skin. Thus, median MAZ depth in hydrated skin was 10% and 14% lower than in control areas at 10 and 30 mJ/mb pulse energy, respectively (10 mJ: 210 vs. 180 µm (p < 0.001); 30 mJ: 335 vs. 300 µm (p < 0.001)). CONCLUSION: Skin hydration status can exert a minimal impact on patterns of microthermal injury produced by fractional CO2 lasers, although the clinical implication in the context of laser therapy requires further study.

Characterization of Patient-Derived GNAQ Mutated Endothelial Cells from Capillary Malformations.

Capillary malformations (CM) (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and postcapillary venules. CMs are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cells of CMs, providing an opportunity for the development of targeted therapies. However, there is currently limited in-depth mechanistic insight into the pathophysiology and a lack of preclinical research approaches. In a monocenter exploratory study of 17 adult patients with CMs, we found somatic sequence variants in the GNAQ (p.R183Q, p.R183G, or p.Q209R) or GNA11 (p.R183C) genes. We applied an endothelial-selective cell isolation protocol to culture primary endothelial cells from skin biopsies from these patients. We successfully expanded patient-derived cells in culture in 3 of the 17 cases while maintaining endothelial specificity as demonstrated by vascular endothelial-cadherin immunostainings. In addition, we tested the angiogenic capacity of endothelial cells from a patient with a GNAQ (p.R183G) sequence substitution. These proof-of-principle results reveal that primary cells isolated from CMs may represent a functional research model to investigate the role of endothelial somatic mutations in the etiology of CMs, but improved isolation and culture methodologies are urgently needed to advance the field.

Current Practice in Keloid Treatment: a Survey of Dutch Dermatologists and Plastic Surgeons.

BACKGROUND: Several therapeutic options are available for the treatment of keloids, but it remains unclear which treatment options are most commonly used by practitioners. OBJECTIVE: To explore the prevailing treatment for different keloid phenotypes among dermatologists and plastic surgeons in the Netherlands. METHODS: Members of the Dutch society for Plastic surgery and the Dutch society for Dermatology and Venereology were asked to participate. Questions elaborated on the treatment for a small and a large keloid on the mandibula and multiple keloids on the chest. RESULTS: One hundred forty-three responses were obtained. Heterogeneity in treatment was extremely high for the small, large, and multiple keloids with 27, 35, and 33 various first choices, respectively. Intralesional corticosteroids were most often chosen for all 3 different keloid phenotypes. These were mostly (61%) administered as monotherapy for the small keloid and mostly combined with other treatments for the large keloid (19%) and multiple keloids (43%). Surgery was chosen regularly (22%) for the large keloid, mostly combined with intralesional corticosteroids (10%) or brachytherapy (8.4%). CONCLUSION: Keloid treatment is very heterogeneous among dermatologists and plastic surgeons, even in a relatively small country as the Netherlands. Moreover, the treatment choice depends on the keloid phenotype.

Trained immunity in the pathogenesis of vitiligo.

Vitiligo is caused by an autoimmune reaction against melanocytes leading to melanocyte loss. The cause of vitiligo is an interaction between genetic susceptibility and environmental factors. Both the adaptive immune system-through cytotoxic CD8+ T cells and melanocyte specific antibodies-and the innate immune system are involved in these immune processes in vitiligo. While recent data stressed the importance of innate immunity in vitiligo, the question remains why vitiligo patients' immune response becomes overly activated. Could a long-term increase in innate memory function, described as trained immunity after vaccination and in other inflammatory diseases, play a role as an enhancer and continuous trigger in the pathogenesis of vitiligo? After exposure to certain stimuli, innate immune system is able to show an enhanced immunological response to a secondary trigger, indicating a memory function of the innate immune system, a concept termed trained immunity. Trained immunity is regulated by epigenetic reprogramming, including histone chemical modifications and changes in chromatin accessibility that cause sustained changes in the transcription of specific genes. In responses to an infection, trained immunity is beneficial. However, there are indications of a pathogenic role of trained immunity in inflammatory and autoimmune diseases, with monocytes presenting features of a trained phenotype, resulting in increased cytokine production, altered cell metabolism through mTOR signaling, and epigenetic modifications. This hypothesis paper focusses on vitiligo studies that have shown these indications, suggesting the involvement of trained immunity in vitiligo. Future studies focusing on metabolic and epigenetic changes in innate immune cell populations in vitiligo could help in elucidating the potential role of trained immunity in vitiligo pathogenesis.

Efficacy and safety of needle-free jet injector-assisted intralesional treatments in dermatology-a systematic review.

Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle-Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations.

Intralesional corticosteroid administration in the treatment of keloids: a survey among Dutch dermatologists and plastic surgeons.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line therapy in keloid treatment. However, its clinical results are still highly variable and often suboptimal. Treatment results may strongly be influenced by various ways of ICA. OBJECTIVE: To explore the prevailing practice of ICA in keloid treatment among dermatologists and plastic surgeons in the Netherlands. METHODS: The survey was constructed based on a scoping review on ICA in keloid treatment. Members of the Dutch Society for Plastic surgery and the Dutch Society for Dermatology and Venereology were asked to participate. RESULTS: One hundred and thirty-six responses were obtained. One hundred and thirty (95.6%) participants used triamcinolone acetonide. The majority (54.7%) did not use local anesthesia for pain reduction. Reported corticosteroid dosing that one would inject in one specific keloid differed by a factor of 40. Treatment intervals varied from 1 week to more than 8 weeks. The keloid center was most often injected (46.9%), followed by subepidermal (18.0%). CONCLUSIONS: A wide variety in ICA for keloids is noted among dermatologists and plastic surgeons, even in a limited geographic region and when evidence points toward an optimal way of treatment. Future studies and better implementation of existing evidence may reduce variation in ICA and optimize its treatment results.

A core outcome domain set for clinical research on capillary malformations (the COSCAM project): an e-Delphi process and consensus meeting.

BACKGROUND: There is limited evidence on the best available treatment options for capillary malformations (CMs), mainly due to the absence of uniform outcome measures in trials on therapies. A core outcome set (COS) enables standard reporting of trial outcomes, which facilitates comparison of treatment results. OBJECTIVES: To develop a core outcome domain set (CDS), as part of a core outcome set (COS), for clinical research on CMs. METHODS: Sixty-seven potentially relevant outcome subdomains were recognized based on the literature, focus group sessions, and input from the COSCAM working group. These outcome subdomains were presented in an online Delphi study to CM experts (medical specialists and authors of relevant literature) and (parents of) patients with CM (international patient associations). During three e-Delphi study rounds, the participants repeatedly scored the importance of these outcome subdomains on a seven-point Likert scale. Participants could also propose other relevant outcome subdomains. Consensus was defined as ≥ 80% agreement as to the importance of an outcome subdomain among both stakeholder groups. The CDS was finalized during an online consensus meeting. RESULTS: In total 269 participants from 45 countries participated in the first e-Delphi study round. Of these, 106 were CM experts from 32 countries, made up predominantly of dermatologists (59%) and plastic surgeons (18%). Moreover, 163 (parents of) patients with CM from 28 countries participated, of whom 58% had Sturge-Weber syndrome. During the two subsequent e-Delphi study rounds, 189 and 148 participants participated, respectively. After the entire consensus process, consensus was reached on 11 outcome subdomains: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. CONCLUSIONS: We recommend the CDS to be used as a minimum reporting standard in all future trials of CM therapy. Our next step will be to select suitable outcome measurement instruments to score the core outcome subdomains. What is already known about this topic? Besides physical and functional sequelae, capillary malformations (CMs) often cause emotional and social burden. The lack of uniform outcome measures obstructs proper evaluation and comparison of treatment strategies. As a result, there is limited evidence on the best available treatment options. The development of a core outcome set (COS) may improve standardized reporting of trial outcomes. What does this study add? A core outcome domain set (CDS), as part of a COS, was developed for clinical research on CMs. International consensus was reached on the recommended core outcome subdomains to be measured in CM trials: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. This CDS enables the next step in the development of a COS, namely to reach consensus on the core outcome measurement instruments to score the core outcome subdomains. What are the clinical implications of this work? The obtained CDS will facilitate standardized reporting of treatment outcomes, thereby enabling proper comparison of treatment results. This comparison is likely to provide more reliable information for patients about the best available treatment options.

Clinical endpoints of needle-free jet injector treatment: An in depth understanding of immediate skin responses.

OBJECTIVES: Needle-free jet injectors have been used in dermatological practice for many years. However, predefined clinical endpoints that guide physicians to choose optimal device settings have not been clearly defined. Here, we evaluate immediate skin responses as clinical endpoints for needle-free jet injector treatments. METHODS: We injected methylene blue in ex vivo human skin using an electronically-controllable pneumatic injector (EPI; 3-6 bar, 50-130 µl; n = 63), and a spring-loaded jet injector (SLI) with fixed settings (100 µl; n = 9). We measured the immediate skin papule (3D-camera), residual surface fluid (pipette), dermal dye distribution by estimating depth and width, and subcutaneous dye deposition. RESULTS: EPI with 4 bar and 100 µl resulted in the largest skin papule of 48.7 mm3 (35.4-62.6 mm3 ) and widest dermal distribution of 8.0 mm (5.5-9.0 mm) compared to EPI with 6 bar and 100 µl (p < 0.001, p = 0.018, respectively). The skin papule volume showed a significant moderate to high positive correlation with the width and depth of dye distribution in the dermis (rs = 0.63, rs = 0.58, respectively; p < 0.001 for both correlations). SLI showed high variability for all outcome measures. Finally, a trend was observed that a small skin papule (≤7 mm) and little residual surface fluid (≤10% of injection volume) were warning signs for subcutaneous deposition. CONCLUSIONS: The immediate skin papule and residual surface fluid correspond with dermal drug deposition and are relevant clinical endpoints for needle-free jet injector treatments in dermatological practice.

Ultrafine particle concentrations during laser hair removal: Effectiveness of smoke evacuators.

BACKGROUND AND OBJECTIVES: Laser smoke is a biohazard that contains potentially dangerous toxic and biological components. In laser hair removal (LHR), practitioners undergo prolonged exposure as this procedure is widely used without protective measures. Little is known about the effect of smoke evacuators on ultrafine particle concentrations during LHR. This study aims to assess the effect of different laser devices and different smoke evacuators on the ultrafine particle concentrations in the room during LHR. STUDY DESIGN/MATERIALS AND METHODS: In a prospective observational study, we included patients with skin phototypes 2-4 for 755 nm Alexandrite LHR at two study sites, receiving treatment in axillae and pubic areas. Ultrafine particle concentrations were measured during LHR for two different alexandrite lasers, with and without an external smoke evacuator. Moreover, we assessed a device for LHR with a smoke evacuator integrated into the handpiece. Primary outcomes were the concentration of ultrafine particles (0.2-0.3 µm) per m3 at 1 min after initiation of treatment and maximum concentrations. RESULTS: A total of 15 patients were recruited for routine LHR. Without a smoke evacuator, already at 1 minute after treatment onset, ultrafine particle concentrations rapidly increased. Both external and integrated smoke evacuators were highly effective with a 3.7-7-fold decrease in maximal particle count. Similarly, maximal particle concentrations remained low with both smoke evacuators. At both study sites, particle concentrations decreased slowly (8 min for 50% reduction) when treatment stopped. CONCLUSION: LHR procedures generated an increase of ultrafine particles. Both the external and integrated smoke evacuators are highly effective in controlling ultrafine particle concentrations during LHR. Once particle concentrations are elevated and the process had been completed, clearance of ultrafine particles is rather slow.

Needle-free jet injection-induced small-droplet aerosol formation during intralesional bleomycin therapy.

OBJECTIVES: Needle-free jet injectors are frequently used in dermatological practice. Injection-generated small-droplet aerosols could be harmful upon inhalation when chemotherapeutics, like bleomycin, are used. Here, we aim to explore jet injector-induced small-droplet aerosol formation of bleomycin in relation to air ventilation and to provide safety measures for clinical practice. MATERIALS AND METHODS: With a professional particle sensor, we measured airborne aerosol particles (0.2-10.0 µm) after electronic pneumatic injection (EPI), spring-loaded jet injection (SLI), and needle injection (NI) of bleomycin and saline (100 µl) on ex vivo human skin. Three levels of air ventilation were explored: no ventilation, room ventilation, and room ventilation with an additional smoke evacuator. RESULTS: EPI and SLI induced significant small-droplet aerosol formation compared with none after NI (0.2-1.0 µm; no ventilation). The largest bleomycin aerosol generation was observed for the smallest particles (0.2-1.0 µm) with 673.170 (528.802-789.453) aerosol particles/liter air (EPI; no ventilation). Room ventilation and smoke evacuation led to a reduction of ≥99% and 100% of measured aerosols, respectively. CONCLUSION: Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel. Room ventilation and smoke evacuation are effective safety measures when chemotherapeutics are used in clinical practice.

Therapeutic Strategies for Untreated Capillary Malformations of the Head and Neck Region: A Systematic Review and Meta-Analyses.

BACKGROUND: Capillary malformations of the head and neck region often cause psychological and physical burden. As the effectiveness of modern laser and light therapies is still suboptimal, patients often seek different therapeutic strategies. Other recognized, but not routinely proposed therapies include cosmetic camouflage, surgery, and medical tattooing. Information on therapeutic outcomes is currently lacking for patients to adequately participate in the treatment decision-making process. OBJECTIVE: The objective of this systematic review was to review the effectiveness and safety of recognized therapies for untreated capillary malformations of the head and neck: laser and light treatment modalities, photodynamic therapy, cosmetic camouflage, medical tattooing, and surgery. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to 16 December, 2020 for observational and experimental studies examining recognized therapies for untreated capillary malformations of the head and neck. Two reviewers independently evaluated the risk of bias of included studies. Predefined treatment and safety outcomes of pooled data were scored using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 48 observational and three randomized studies (totaling 3068 patients), evaluating nine different therapies. No studies on surgery or cosmetic camouflage matched our inclusion criteria. The pooled proportion of patients reaching a ≥75% clearance was 43% (95% confidence interval 24-64%; I2 = 55%) for the pulsed dye laser after three to eight treatment sessions (GRADE score: very low). Other therapies were less effective. Hyperpigmentation was most frequently described after the pulsed dye laser (incidences up to 40%). Pain was most common after photodynamic therapy, yet the intensity was unreported. Substantial heterogeneity among studies as to patient characteristics and outcomes limited pooling and data comparisons. CONCLUSIONS: The pulsed dye laser seems preferable for treatment-naive capillary malformations of the head and neck region, yet demonstrates greater hyperpigmentation rates compared with other therapies. Our results are, however, based on low-quality evidence. Future studies using uniform outcome measures and validated metrics are warranted for study comparability. Based on this systematic review, clinicians and patients should be aware of the limited evidence about the available options when making (shared) treatment decisions for capillary malformations. TRIAL REGISTRATION: Review registration number PROSPERO database: CRD42020199445.

Treatment Outcome Measurement Instruments for Port Wine Stains: A Systematic Review of Their Measurement Properties.

BACKGROUND: A plethora of outcome measurement instruments (OMIs) are being used in port wine stain (PWS) studies. It is currently unclear how valid, responsive, and reliable these are. OBJECTIVES: The aim of this systematic review was to appraise the content validity and other measurement properties of OMIs for PWS treatment to identify the most appropriate instruments and future research priorities. METHODS: This study was performed using the updated Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology and adhered to PRISMA guidelines. Comprehensive searches in Medline and Embase were performed. Studies in which an OMI for PWS patients was developed or its measurement properties were evaluated were included. Two investigators independently extracted data and assessed the quality of included studies and instruments to perform qualitative synthesis of the evidence. RESULTS: In total, 1,034 articles were screened, and 77 full-text articles were reviewed. A total of 8 studies were included that reported on 6 physician-reported OMIs of clinical improvement and 6 parent- or patient-reported OMIs of life impact, of which 3 for health-related quality of life and 1 for perceived stigmatization. Overall, the quality of OMI development was inadequate (63%) or doubtful (37%). Each instrument has undergone a very limited evaluation in PWS patients. No content validity studies were performed. The quality of evidence for content validity was very low (78%), low (15%), or moderate (7%), with sufficient comprehensibility, mostly sufficient comprehensiveness, and mixed relevance. No studies on responsiveness, minimal important change, and cross-cultural validity were retrieved. There was moderate- to very low-quality evidence for sufficient inter-rater reliability for some clinical PWS OMIs. Internal consistency and measurement error were indeterminate in all studies. CONCLUSIONS: There was insufficient evidence to properly guide outcome selection. Additional assessment of the measurement properties of OMIs is needed, preferentially guided by a core domain set tailored to PWS.