Whipps Cross University Hospital

The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.

OBJECTIVES: To determine (i) risk factors in the development of third degree obstetric tears and (ii) the success of primary sphincter repair. DESIGN: (i) Retrospective analysis of obstetric variables in 50 women who had sustained a third degree tear, compared with the remaining 8553 vaginal deliveries during the same period. (ii) Women who had sustained a third degree tear and had primary sphincter repair and control subjects were interviewed and investigated with anal endosonography, anal manometry, and pudendal nerve terminal motor latency measurements. SETTING: Antenatal clinic in teaching hospital in inner London. SUBJECTS: (i) All women (n = 8603) who delivered vaginally over a 31 month period. (ii) 34 women who sustained a third degree tear and 88 matched controls. MAIN OUTCOME MEASURES: Obstetric risk factors, defecatory symptoms, sonographic sphincter defects, and pudendal nerve damage. RESULTS: (i) Factors significantly associated with development of a third degree tear were: forceps delivery (50% v 7% in controls; P = 0.00001), primiparous delivery (85% v 43%; P = 0.00001), birth weight > 4 kg (P = 0.00002), and occipito-posterior position at delivery (P = 0.003). No third degree tear occurred during 351 vacuum extractions. Eleven of 25 (44%) women who were delivered without instruments and had a third degree tear did so despite a posterolateral episiotomy. (ii) Anal incontinence or faecal urgency was present in 16 women with tears and 11 controls (47% v 13%; P = 0.00001). Sonographic sphincter defects were identified in 29 with tears and 29 controls (85% v 33%; P = 0.00001). Every symptomatic patient had persistent combined internal and external sphincter defects, and these were associated with significantly lower anal pressures. Pudendal nerve terminal motor latency measurements were not significantly different. CONCLUSIONS: Vacuum extraction is associated with fewer third degree tears than forceps delivery. An episiotomy does not always prevent a third degree tear. Primary repair is inadequate in most women who sustain third degree tears, most having residual sphincter defects and about half experiencing anal incontinence, which is caused by persistent mechanical sphincter disruption rather than pudendal nerve damage. Attention should be directed towards preventive obstetric practice and surgical techniques of repair.

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BACKGROUND: Children with bilateral permanent hearing impairment often have impaired language and speech abilities. However, the effects of universal newborn screening for permanent bilateral childhood hearing impairment and the effects of confirmation of hearing impairment by nine months of age on subsequent verbal abilities are uncertain. METHODS: We studied 120 children with bilateral permanent hearing impairment identified from a large birth cohort in southern England, at a mean of 7.9 years of age. Of the 120 children, 61 were born during periods with universal newborn screening and 57 had hearing impairment that was confirmed by nine months of age. The primary outcomes were language as compared with nonverbal ability and speech expressed as z scores (the number of standard deviations by which the score differed from the mean score among 63 age-matched children with normal hearing), adjusted for the severity of the hearing impairment and for maternal education. RESULTS: Confirmation of hearing impairment by nine months of age was associated with higher adjusted mean z scores for language as compared with nonverbal ability (adjusted mean difference for receptive language, 0.82; 95 percent confidence interval, 0.31 to 1.33; and adjusted mean difference for expressive language, 0.70; 95 percent confidence interval, 0.13 to 1.26). Birth during periods with universal newborn screening was also associated with higher adjusted z scores for receptive language as compared with nonverbal ability (adjusted mean difference, 0.60; 95 percent confidence interval, 0.07 to 1.13), although the z scores for expressive language as compared with nonverbal ability were not significantly higher. Speech scores did not differ significantly between those who were exposed to newborn screening or early confirmation and those who were not. CONCLUSIONS: Early detection of childhood hearing impairment was associated with higher scores for language but not for speech in midchildhood.

OBJECTIVE: To examine the natural history, role of risk factors, and incidence of knee osteoarthritis (OA) in a prospective study of women from a population cohort. METHODS: Women from the Chingford Study who had been recruited in 1989 were followed up with knee radiographs 4 years later. A total of 715 paired radiographs (71% of the original sample) were graded for osteophytes and 644 for joint space narrowing (JSN). Women whose radiographs had been graded as 0 in 1989 and as > or =14 years later were classified as having incident disease. Incident cases were compared with controls for associations with a number of risk factors. RESULTS: Eighty-one women (12.6%) developed JSN of the knee, equating to an incidence of 3.1% per year. No clear risk factors for JSN were identified. Reproducibility of measures of joint space is poor, however, leading to inaccuracy of definition. Incident knee osteophytes developed in 95 women (133%), equating to an incidence of 3.3% per year. Compared with controls, women with incident knee osteophytes were older, heavier, and had more hand OA and knee symptoms. Women in the top tertile of obesity (body mass index >26.4) had a significantly increased risk of incident knee osteophytes (odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.29-4.39). Incident knee osteophytes increased by 20% per 5-year age increase. A nonsignificant protective effect for incident knee osteophytes was seen with current estrogen replacement therapy (ERT) (OR 0.41, 95% CI 0.12-1.42). No effect was associated with smoking, physical activity, hysterectomy, or previous knee injury. CONCLUSION: Obesity and aging are associated with a high risk of new knee OA developing in women. Evidence of a protective effect of ERT was seen. No clear association was found for incident JSN, suggesting that different etiologic mechanisms are operating or that standard radiographs are an inaccurate measure of incident narrowing.

OBJECTIVE: To examine the role of low-grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee. METHODS: We used a new, high-sensitivity, automated monoclonal antibody immunoassay for the classic acute-phase protein, C-reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44-67) on entry into a population-based study of OA in Chingford, North London. In those defined radiologically as "cases," the knee radiographs were repeated after 4 years. RESULTS: Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren-Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0-5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3-1.8) (P < 0.001). Median levels of CRP were higher in the 31 women whose disease progressed at least 1 Kellgren-Lawrence grade (median 2.6 mg/liter, IQR 1.9-4.6), compared with the 39 whose disease did not (median 1.3 mg/liter, IQR 0.6-2.4) (P = 0.006) . The significance of these differences persisted after adjustment for age, weight, height, smoking, knee pain, or injury. Classifying disease by the presence of joint space narrowing or osteophytes alone produced similar results. CONCLUSION: CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low-grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.

OBJECTIVE: To estimate the risk of osteoarthritis (OA) of the hip and knee due to long-term weight-bearing sports activity in ex-elite athletes and the general population. METHODS: A retrospective cohort study was conducted of 81 female ex-elite athletes (67 middle- and long-distance runners, and 14 tennis players), currently ages 40-65, recruited from original playing records, and 977 age-matched female controls, taken from the age-sex register of the offices of a group general practice in Chingford, Northeast London, England. The definition of OA included radiologic changes (joint space narrowing and osteophytosis) in the hip joints, patellofemoral (PF) joints, and tibiofemoral (TF) joints. RESULTS: Compared with controls of similar age, the ex-athletes had greater rates of radiologic OA at all sites. This association increased further after adjustment for height and weight differences, and was strongest for the presence of osteophytes at the TF joints (odds ratio [OR] 3.57, 95% confidence interval [95% CI] 1.89-6.71), at the PF joints (OR 3.50, 95% CI 1.80-6.81), narrowing at the PF joints (OR 2.97, 95% CI 1.15-7.67), femoral osteophytes (OR 2.52, 95% CI 1.01-6.26), and hip joint narrowing (OR 1.60, 95% CI 0.73-3.48), and was weakest for narrowing at the TF joints (OR 1.17, 95% CI 0.71-1.94). No clear risk factors were seen within the ex-athlete groups, although the tennis players tended to have more osteophytes at the TF joints and hip, but the runners had more PF joint disease. Within the control group, a small subgroup of 22 women who reported long-term vigorous weight-bearing exercise had risks of OA similar to those of the ex-athletes. Ex-athletes had similar rates of symptom reporting but higher pain thresholds than controls, as measured by calibrated dolorimeter. CONCLUSION: Weight-bearing sports activity in women is associated with a 2-3-fold increased risk of radiologic OA (particularly the presence of osteophytes) of the knees and hips. The risk was similar in ex-elite athletes and in a subgroup from the general population who reported long-term sports activity, suggesting that duration rather than frequency of training is important.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

In many health care systems globally, cancer care is driven by multidisciplinary cancer teams (MDTs). A large number of studies in the past few years and across different literature have been performed to better understand how these teams work and how they manage patient care. The aim of our literature review is to synthesize current scientific and clinical understanding on cancer MDTs and their organization; this, in turn, should provide an up-to-date summary of the current knowledge that those planning or leading cancer services can use as a guide for service implementation or improvement. We describe the characteristics of an effective MDT and factors that influence how these teams work. A range of factors pertaining to teamwork, availability of patient information, leadership, team and meeting management, and workload can affect how well MDTs are implemented within patient care. We also review how to assess and improve these teams. We present a range of instruments designed to be used with cancer MDTs - including observational tools, self-assessments, and checklists. We conclude with a practical outline of what appears to be the best practices to implement (Dos) and practices to avoid (Don'ts) when setting up MDT-driven cancer care.

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Abstract Objective: To compare tension-free open mesh hernioplasty under local anaesthetic with transabdominal preperitoneal laparoscopic hernia repair under general anaesthetic. Design: A randomised controlled trial of 403 patients with inguinal hernias. Setting: Two acute general hospitals in London between May 1995 and December 1996. Subjects: 400 patients with a diagnosis of groin hernia, 200 in each group. Main outcome measures: Time until discharge, postoperative pain, and complications; patients' perceived health (SF-36), duration of convalescence, and patients' satisfaction with surgery; and health service costs. Results: More patients in the open group (96%) than in the laparoscopic group (89%) were discharged on the same day as the operation (χ 2 =6.7; 1 df; P=0.01). Although pain scores were lower in the open group while the effect of the local anaesthetic persisted (proportional odds ratio at 2 hours 3.5 (2.3 to 5.1)), scores after open repair were significantly higher for each day of the first week (0.5 (0.3 to 0.7) on day 7) and during the second week (0.7 (0.5 to 0.9)). At 1 month there was a greater improvement (or less deterioration) in mean SF-36 scores over baseline in the laparoscopic group compared with the open group on seven of eight dimensions, reaching significance on five. For every activity considered the median time until return to normal was significantly shorter for the laparoscopic group. Patients randomised to laparoscopic repair were more satisfied with surgery at 1 month and 3 months after surgery. The mean cost per patient of laparoscopic repair was £335 (95% confidence interval £228 to £441) more than the cost of open repair. Conclusion: This study confirms that laparoscopic hernia repair has considerable short term clinical advantages after discharge compared with open mesh hernioplasty, although it was more expensive. Key messages In the 4 hours after surgery laparoscopic hernia repair with general anaesthesia causes more pain than open repair with local anaesthesia (mainly because of the anaesthesia used) and necessitates longer stay in hospital. Laparoscopic hernia repair, however, causes less pain than open hernia repair during the first 2 weeks after discharge Laparoscopic hernia repair results in fewer episodes of wound infection, persistent local pain, genital swelling, numbness, and constipation than open repair. Urinary disturbances are more common after laparoscopic than after open repair Patients' perception of health 1 month after the operation (assessed with the SF-36) and satisfaction with treatment is superior for laparoscopic patients who also have a shorter period of convalescence after surgery The health service cost of day case laparoscopic repair is £335 more than the cost of open mesh hernioplasty performed on a day case basis

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

<h3>Objectives</h3> To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). <h3>Methods</h3> Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. <h3>Results</h3> Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p&lt;0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<i>&lt;</i>0.01 for 300 mg with LD and 150 mg without LD and p&lt;0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. <h3>Conclusion</h3> S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. <h3>Trial registration number</h3> NCT02404350; Results.

Hemorrhoidal disease (HD) is the most common proctological disease in the Western countries. However, its real prevalence is underestimated due to the frequent self-medication.The aim of this consensus statement is to provide evidence-based data to allow an individualized and appropriate management and treatment of HD. The strategy used to search for evidence was based on application of electronic sources such as MEDLINE, PubMed, Cochrane Review Library, CINAHL, and EMBASE.These guidelines are inclusive and not prescriptive.The recommendations were defined and graded based on the current levels of evidence and in accordance with the criteria adopted by American College of Chest Physicians. The recommendations were graded A, B, and C.

SUMMARY The aim of the study was to develop a simple and reproducible self‐reporting questionnaire that identifies individuals with hypermobility. Two hundred and twelve consecutive hypermobile female new attendees to the hypermobility clinic at two London teaching hospitals and a random selection of 57 healthy volunteers completed a 10‐part questionnaire. Questions were selected from clinical experience (RG), and assessed musculoskeletal symptoms and past and present physical agility. Of the 212 cases, 30 were hypermobile with no other underlying disorder and 182 fulfilled the 1998 Brighton criteria for benign joint hypermobility syndrome (BJHS). Odds ratios for the presence of hypermobility were calculated for each question. Six questions were found to be significant and the model of ‘best fit’ for sensitivity and specificity contained five of these. To demonstrate the reproducibility of the five‐part questionnaire a second cohort of 170 hypermobile cases with BJHS and 50 controls was surveyed. Analysis demonstrated that a positive answer to any two questions in the five‐part questionnaire gave the highest combined sensitivity and specificity for detecting hypermobility. The sensitivity and specificity was 84% and 89% respectively in the first cohort and reproduced with values of 84% and 80% in the second cohort. Overall the questionnaire correctly identified 84% of all cases and controls. This simple and reproducible questionnaire for detecting hypermobility could be of particular use as an adjunct in the clinical assessment of chronic, diffuse pain syndromes where hypermobility is often missed yet is potentially treatable.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Abstract Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency. Significance: Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population. See related commentary by Italiano, p. 14. This article is highlighted in the In This Issue feature, p. 1

PURPOSE: Transanal hemorrhoidal dearterialization consists of a Doppler-guided ligation of the distal branches of the rectal arteries. The aim of this review is to assess the current evidence on dearterialization, establish the safety and efficacy of the technique, define its indications, and identify its possible advantages and limitations. METHODS: All published studies on dearterialization without language restrictions were reviewed systematically. Primary outcome measures were postoperative pain and hemorrhoidal recurrences. RESULTS: Seventeen articles including a total of 1,996 patients were analyzed. In general, the quality of the studies was low. Operating time ranged between 5 and 50 minutes. Hospital stay was one day for most patients, whereas the return to normal activities was between two and three days in most cases. Postoperative pain was present in 18.5% of patients. Three patients experienced significant postoperative hemorrhages. There were no other major complications. The overall recurrence rate was 9.0% for prolapse, 7.8% for bleeding, and 4.7% for pain at defecation. The recurrence rate at one year or more was 10.8% for prolapse, 9.7% for bleeding, and 8.7% for pain at defecation. When reported as a function of the hemorrhoidal grade, the recurrence rate was higher for fourth-degree hemorrhoids (range, 11.1-59.3%). CONCLUSION: Transanal hemorrhoidal dearterialization appears to be a potential treatment option for second-degree and third-degree hemorrhoids. Clinical trials and longer follow-up comparing it with other procedures used to treat hemorrhoids are needed to establish a possible role for this technique.

A brief description is presented of a computer simulation of the Rayleigh distributed fast fading encountered in mobile radio. This simulation should be of interest to all those whose studies involve parameters of a mobile system that interact strongly with the radio environment.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.