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Abstract Background Pain is common in the genetic skin fragility disorder epidermolysis bullosa (EB), from skin and mucosal injury and inflammation as well as extra-mucocutaneous sites. Individuals living with EB have identified pain as a priority for better treatments. Objectives The Prospective EB Longitudinal Evaluation Study (PEBLES) is a prospective register study exploring the natural history of RDEB across all ages from birth to death. Here, we investigated the characteristics and treatment of pain in different RDEB subtypes. Methods Information was collected from individuals with different RDEB subtypes over an 8-year period. Data included visual analogue scale (VAS) ratings of background and procedural pain, its location, intensity and impact on sleep, as well as pain medication. Disease severity scores and quality of life measures were correlated to pain scores. Results Sixty-one participants (13 children, 48 adults) completed a total of 361 reviews. Pain was common, experienced by 93% of participants at index review, with 80% suffering both background and procedural pain. Across all RDEB patients, the median VAS for background pain was 40 (out of 100) [interquartile range 20,60] and for those having regular dressing changes, median procedural pain was 52 [40,80]. Severe (RDEB-S) and pruriginosa (RDEB-Pru) groups had the greatest increase in procedural compared to background pain of 20 and 22 VAS points, respectively. Correlations between disease severity and quality of life impairment were observed across most groups, particularly RDEB-S. Over half of those studied experienced pain frequently or constantly, and in one third pain disturbed sleep at least 4 nights per week. Skin was the commonest source of pain in all subtypes except inversa RDEB where the mouth was the main site. Despite frequent and severe pain, one third of participants used no medication for pain and, in those that did, pain levels remained high suggesting ineffectiveness of current pain management approaches and a significant unmet need in RDEB. Conclusion The frequency, severity, and impact of pain in all RDEB patients is significant, particularly in RDEB-S and RDEB-Pru. Our findings highlight that current RDEB pain management is poorly effective and that further research is needed to address this symptom.

Abstract Background Itch is common and distressing in epidermolysis bullosa (EB) but has not previously been studied in depth in different recessive dystrophic EB (RDEB) subtypes. Objectives As part of a prospective register study of the natural history of RDEB we explored features of itch, medications used, and correlation with disease severity and quality of life. Methods Fifty individuals with RDEB aged 8 years and above completed the Leuven Itch Scale (LIS) (total 243 reviews over a 7-year period). Data included itch frequency, severity, duration, distress, circumstances, consequences, itch surface area and medications for itch. The iscorEB disease severity score and the validated EB quality of life tool, QOLEB, were compared to LIS domains and analysed by RDEB subtype. Results Itch was frequent, present in the preceding month in 93% of reviews. Itch severity and distress were significantly greater in severe (RDEB-S) and pruriginosa (RDEB-Pru) subtypes compared to intermediate RDEB (RDEB-I). Itch medications were reported in just over half of reviews including emollients, topical corticosteroids and antihistamines; the proportion of participants not using medication despite frequent pruritus suggests limited efficacy. In inversa RDEB (RDEB-Inv) and RDEB-I, LIS domains correlated with iscorEB and QOLEB. In contrast to previous studies, correlations were lacking in RDEB-S suggesting that global disease burden relatively reduces the contribution of itch. Conclusions This comprehensive study of RDEB-associated itch highlights differences between RDEB subtypes, suggests an unmet need for effective treatments and could serve as control data for future clinical trials incorporating itch as an endpoint.

Abstract Background Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin fragility disorder requiring multidisciplinary management. Information regarding costs of current standard treatment is scant. Objectives As part of a longitudinal natural history study, we explored the community care costs of UK patients with different forms of RDEB. Methods Fifty‐nine individuals with RDEB provided detailed information on multiple facets of RDEB including disease severity scores (iscorEB, BEBS) and patient reported outcomes (quality of life evaluation in epidermolysis bullosa, iscorEB patient questionnaire). Costs data included time spent doing dressings, frequency of dressing changes, details of materials used, and paid and unpaid care. Results Overall costs of dressing materials and associated care were high in RDEB. Median annual costs across all subtypes for those using dressings (n = 51) were over £26 000. For severe RDEB (RDEB‐S), median costs were almost £90 000 per annum, with a median of 18 h per week spent on dressing changes. Half of working‐age adults with RDEB were unemployed and 39% of carers were unable to take on full‐time or part‐time paid employment, adding to indirect costs and the financial burden from RDEB on families and society. Conclusions The findings demonstrate the high costs of care of RDEB, particularly for RDEB‐S. The current expense supports the drive to develop new therapies which accelerate wound healing and diminish total wound burden, thereby reducing costs of dressings and care. While costly to bring to market, these might ultimately reduce the overall cost of treatment and also the impact on individuals living with this rare disease. The data also highlight the need for adequate reimbursement for EB care which can place significant financial strain on families.

Objective: The purpose of this study is to determine the diagnostic accuracy of a surgeon-performed thyroid ultrasound reported using Kwak Thyroid Imaging Reporting and Data System (Kwak TIRADS) in identifying thyroid malignancy. Patients and Methods: This is a retrospective cohort study of patients who underwent preoperative thyroid ultrasound by a surgeon and subsequently underwent thyroidectomy from January 2018 – March 2020 in UP-PGH, Department of Surgery. Correlation between ultrasonographic features and Kwak TIRADS categories with malignancy were analyzed using chi square (univariate analysis) and logistic regression (multivariate analysis). Results: A total of 174 patients with thyroid nodules at least 1 cm in widest diameter were included in the study. There were 85 patients with malignant thyroid disease and 89 patients with benign nodules. Solid composition, hypoechogenicity/marked hypoechogenicity, lobulated/irregular margins, rim/microcalcifications, and shape taller than wide were significantly associated with thyroid malignancy on univariate analysis (all p-values < 0.001). However, only solid composition, hypoechogenicity/marked hypoechogenicity, and irregular/lobulated margins were significantly associated with thyroid malignancy on multivariate analysis (p-values < 0.001, 0.002 and 0.011, respectively). On the other hand, Kwak TIRADS categories 4a and above are significantly associated with thyroid malignancy (all p-values < 0.001), with the risk of malignancy increasing as the Kwak TIRADS category increases. Sensitivity, specificity, PPV and negative NPV are optimal when cutoff for further workup is set at Kwak TIRADS 4a. Conclusions: A surgeon performed thyroid ultrasonography reported using Kwak TIRADS classification can be utilized as a guide in the management of thyroid nodules. The consideration of Kwak TIRADS 4a as a cutoff level for further workup is recommended.

Objective: Leiomyosarcoma (LMS), a sarcoma with smooth muscle differentiation rarely affects the oral cavity due to the paucity of smooth muscle tissues in the region. Because of the intricacy of the anatomy of the oral cavity, tumors affecting this region usually require complex surgeries. We are thus presenting this case, due to the rarity of the disease and its successful treatment by a multidisciplinary team. Case Presentation: A 30-year-old female who was previously diagnosed with a benign smooth muscle neoplasm, had a partial maxillectomy in another institution, came to us for tumor recurrence with a histopathologic report of a smooth muscle tumor of uncertain malignant potential (SmTUMP). Facial and neck CT scan, as well as facial MRI revealed a resectable disease with unremarkable metastatic workup. Results: The clinical aggressiveness of the disease prompted the multidisciplinary team to proceed with infrastructure maxillectomy with the defect covered by a surgical obturator. Final histopathologic report revealed that the tumor is LMS with good margins. Thereafter, the patient underwent adjuvant radiation therapy. At 1-year post-surgery, the patient had minimal speech deficit with good deglutition function and no recurrence. Conclusions: LMS is exceedingly rare in the head and neck region. It is also difficult to diagnose. However, it should be considered a differential diagnosis when dealing with smooth muscle tumors. Successful treatment of this disease entails high index of suspicion and involvement of a multidisciplinary team.

Summary: Background: Social and material deprivation accelerate the development of multimorbidity, yet the mechanisms which drive multimorbidity pathways and trajectories remain unclear. We aimed to examine the association between health inequality, risk factors and accumulation or resolution of LTCs, taking disease sequences into consideration. Methods: We conducted a retrospective cohort of adults aged 18 years and over, registered between April 2005 and May 2020 in general practices in one inner London borough (n = 826,936). Thirty-two long term conditions (LTCs) were selected using a consensus process, based on a definition adapted to the demographic characteristics of the local population. sThe development and resolution of these LTCs were examined according to sociodemographic and clinical risk factors (hypertension; moderate obesity (BMI 30·0–39·9 kg/m2), high cholesterol (total cholesterol > 5 mmol/L), smoking, high alcohol consumption (>14 units per week), and psychoactive substance use), through the application of multistate Markov chain models. Findings: Participants were followed up for a median of 4.2 years (IQR = 1·8 - 8·4); 631,760 (76%) entered the study with no LTCs, 121,424 (15%) with 1 LTC, 41,720 (5%) with 2 LTCs, and 31,966 (4%) with three or more LTCs. At the end of follow-up, 194,777 (24%) gained one or more LTCs, while 45,017 (5%) had resolved LTCs and 27,021 (3%) died. In multistate models, deprivation (hazard ratio [HR] between 1·30 to 1·64), female sex (HR 1·13 to 1·20), and Black ethnicity (HR 1·20 to 1·30; vs White) were independently associated with increased risk of transition from one to two LTCs, and shorter time spent in a healthy state. Substance use was the strongest risk factor for multimorbidity with an 85% probability of gaining LTCs over the next year. First order Markov chains identified consistent disease sequences including: chronic pain or osteoarthritis followed by anxiety and depression; alcohol and substance dependency followed by HIV, viral hepatitis, and liver disease; and morbid obesity followed by diabetes, hypertension, and chronic pain. Interpretation: We examined the relations among 32 LTCs, taking the order of disease occurrence into consideration. Distinctive patterns for the development and accumulation of multimorbidity have emerged, with increased risk of transitioning from no conditions to multimorbidity and mortality related to ethnicity, deprivation and gender. Musculoskeletal disorders, morbid obesity and substance abuse represent common entry points to multimorbidity trajectories.

Introduction As childhood mortality from infectious diseases falls across sub-Saharan Africa (SSA), the burden of disease attributed to surgical conditions is increasing. However, limited data exist on paediatric surgical outcomes in SSA. We compared the outcomes of five common paediatric surgical conditions in SSA with published benchmark data from high-income countries (HICs).Methods A multicentre, international, prospective cohort study was undertaken in hospitals providing paediatric surgical care across SSA. Data were collected on consecutive children (birth to 16 years), presenting with gastroschisis, anorectal malformation, intussusception, appendicitis or inguinal hernia, over a minimum of 1 month, between October 2016 and April 2017. Participating hospitals completed a survey on their resources available for paediatric surgery.The primary outcome was all-cause in-hospital mortality. Mortality in SSA was compared with published benchmark mortality in HICs using χ2 analysis. Generalised linear mixed models were used to identify patient-level and hospital-level factors affecting mortality. A p

Background: Patients admitted to hospital with Covid-19 are at risk of deterioration. The National Early Warning Score (NEWS2) is widely recommended, however it's validity in Covid-19 is not established and indices more specific for respiratory failure may be more appropriate. We aim to describe the physiological antecedents to deterioration, test the predictive validity of NEWS2 and compare this to the ROX index ([SpO2/FiO2]/respiratory rate). Method: A single centre retrospective cohort study of adult patients who were admitted to a medical ward, between 1/3/20 and 30/5/20, with positive results for SARS-CoV-2 RNA. Physiological observations and the NEWS2 were extracted and analysed. The primary outcome was a composite of cardiac arrest, unplanned critical care admission or death within 24 hours. A generalized linear model was used to assess the association of physiological values, NEWS2 and ROX with the outcome. Findings: The primary outcome occurred in 186 patients (26%). In the preceding 24 hours, deterioration was most marked in respiratory parameters, specifically in escalating oxygen requirement; tachypnoea was a late sign, whilst cardiovascular observations remained stable. The area under the receiver operating curve was 0.815 (95% CI 0.804–0.826) for NEWS2 and 0.848 (95% CI 0.837–0.858) for ROX. Applying the optimal level of ROX, the majority of patients triggered four hours earlier than with NEWS2 of 5. Interpretation: NEWS2 may under-perform in Covid-19 due to intrinsic limitations of the design and the unique pathophysiology of the disease. A simple index utilising respiratory parameters can outperform NEWS2 in predicting the occurrence of adverse events.

Background: Globally, there is increasing research on clusters of multimorbidity, but few studies have investigated multimorbidity in urban contexts characterised by a young, multi-ethnic, deprived populations. This study identified clusters of associative multimorbidity in an urban setting. Methods: This is a population-based retrospective cross-sectional study using electronic health records of all adults aged 18 years and over, registered between April 2005 to May 2020 in general practices in one inner London borough. Multiple correspondence analysis and cluster analysis was used to identify groups of multimorbidity from 32 long-term conditions (LTCs). Results: The population included 41 general practices with 826,936 patients registered between 2005 and 2020, with mean age 40 (SD15·6) years. The prevalence of multimorbidity was 21% (n = 174,881), with the median number of conditions being three and increasing with age. Analysis identified five consistent LTC clusters: 1) anxiety and depression (Ratio of within- to between- sum of squares (WSS/BSS

We previously demonstrated corticosteroid administration on the neonatal intensive care unit was associated with reduced lung function at 11 to 14 years of age in children born very prematurely. The objective of this observational study was to assess if lung function remained impaired at 16 to 19 years of age in those who had received postnatal corticosteroids and whether the trajectory of lung function with increasing age differed between those who had and had not received corticosteroids. One hundred and fifty-nine children born prior to 29 weeks of gestational age had comprehensive lung function measurements; 49 had received postnatal dexamethasone. Lung function outcomes were compared between those who had and had not received postnatal dexamethasone after adjustment for neonatal factors. Forced expiratory flow at 75%, 50%, 25% and 25-75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes (total lung capacity and residual volume) were assessed. The majority of results were significantly lower in those who received dexamethasone (between 0.61 to 0.78 standard deviations). Lung function reduced as the number of courses of dexamethasone increased. Between 11 and 14 years and 16 to 19 years, lung function improved in the unexposed group, but forced expiratory flow at 75% of the expired vital capacity and forced expiratory volume in one second deteriorated in those who had received postnatal corticosteroids (p = 0.0006). These results suggest that prematurely born young people who received postnatal corticosteroids may be at risk of premature onset of chronic obstructive pulmonary disease.

Background:. Fingertip amputations are common. This study reports on the outcomes of composite grafts used for fingertip amputations in children, measuring graft take, predictors of graft take, complications, and patient-reported outcomes. Methods:. A retrospective case series of consecutive patients (≤ 16 years) undergoing composite grafts for fingertip amputations in a tertiary pediatric hospital, January 06 to December 16, was performed. Information was collected on amputations, graft take, and complications. Logistic regression was used to analyze factors predicting graft take (partial/complete or failure) including age; amputation level; mechanism and time delay to surgery. Patients were contacted via post or telephone to ask about functional and cosmetic outcomes and their perception of graft take. Results:. One hundred patients [57 (57%) males; mean age, 4.41 ± 3.98 years], presenting with 100 fingertip amputations, met the inclusion criteria. Amputation mechanism was crush in 75 (75%), avulsion in 13 (13%), and laceration in 12 (13%). Thirteen (13%) composite grafts survived completely, 46 (46%) partially, and 41 (41%) failed. Graft survival was higher in children under 4 years (P = 0.016). Seventeen (17%) grafts became infected, 9 (9%) required a reoperation, 9 (9%) had wound healing complications, and 4 (4%) patients developed psychological complications. Patient-reported survival was 33% higher than medical-reported survival. Cosmetic issues were the commonest complication reported by patients. Patients rated fingertips looking 3.5/5 normal, and that they were 4/5 satisfied with the appearance. Most patients were using their fingers normally by 2–6 months. Conclusions:. Composite grafts for fingertip amputations mostly only partially survive, but morbidity is low, patient satisfaction is high, and acceptable cosmetic and functional outcomes are achieved.