What's New After NICE Acne Guidelines.

INTRODUCTION: Acne remains one of the most common inflammatory dermatoses seen worldwide. There are significant challenges when managing acne relating to a variety of factors, including (1) lack of consensus on the use of the numerous available grading systems and outcome measures, (2) appreciation of the numerous areas that relate to severity, (3) the chronic nature of acne which requires a longitudinal approach to management (including both facial and truncal disease), and (4) the need to target acne early to avoid physical and psychosocial scarring. Consideration of these aspects when managing acne should result in improved outcomes. Acne guidelines review the available evidence based on robust clinical trials and are usually supplemented with some expert opinion when evidence is not available. METHODS: In this paper, the UK Acne Working Group reflects on the latest National Institute for Health and Care Excellence (NICE) acne guidelines with a goal of providing additional practical insights. CONCLUSION: The group have identified areas where new evidence has now become available since the formulation of the NICE acne guidelines. This publication considers newly approved acne medications in the UK, guidance on assessing acne severity, approaches to managing truncal acne, acne sequelae, and adult female acne with hormonal therapies.

The National Institute for Health and Care Excellence (NICE) produced acne guidelines in June 2021 for clinicians and patients. New evidence and information on practical aspects of acne management have emerged since this time. A panel of clinicians with expertise in acne discuss herein some areas of interest that may support acne management, some of which could be considered in a second iteration of NICE acne guidelines. These areas include how to assess acne, the medical approach to truncal acne, how clinicians may manage the long-lasting acne sequelae of scarring and darkly pigmented spots, and the use of medical hormonal therapies for women (such as birth control pills) to manage acne that may have a causative contribution of hormone imbalances.

Burden of Respiratory Disease in Pediatric Intensive Care Unit: Experience from a PICU of a Tertiary Care Center in Pakistan.

Introduction: We aimed to determine the burden of respiratory disease by examining clinical profiles and associated predictors of morbidity and mortality of patients admitted to a Pediatric Intensive Care Unit (PICU) in Pakistan, a resource limited country. We also stratified the respiratory diseases as defined by the Pediatric Advanced Life Support (PALS) Classification. Methods: A retrospective study was conducted on children aged 1 month to 18 years who were diagnosed with respiratory illness at the PICU in a tertiary hospital in Karachi, Pakistan. Demographics, essential clinical details including immunization status, and the outcome in terms of mortality or survival were recorded. Predictors of mortality and morbidity including prolonged intubation and mechanical ventilation in the PICU were analyzed using the chi-square test or Fischer's exact test as appropriate. Results: 279 (63.8% male; median age 9 months, IQR 4-36 months) patients were evaluated of which 44.2% were malnourished and 23.3% were incompletely immunized. The median length of stay in the PICU was 3 days (IQR 2-5 days). Pneumonia was the principal diagnosis in 170 patients (62%) and accounted for most deaths. 76/279 (27.2%) were ventilated, and 67/279(24.0%) needed inotropic support. A high Pediatric Risk of Mortality (PRISM) III score, pneumothorax, and lower airway disease were significantly associated with ventilation support. The mortality rate of patients was 14.3%. Predictors of mortality were a high PRISM III score (OR 1.179; 95% CI 1.024-1.358, P=0.022) and a positive blood culture (OR 4.305; 95% CI 1.062-17.448, P=0.041). Conclusion: Pneumonia is a significant contributor of respiratory diseases in the PICU in Pakistan and is the leading cause of morbidity and mortality. A high PRISM III score, pneumothorax, and lower airway disease were predictors for ventilation support. A high PRISM III score and a positive blood culture were predictors of patient mortality in our study.

Defining failure of endoluminal biliary drainage in the era of endoscopic ultrasound and lumen apposing metal stents.

The role of endoscopy in pathologies of the bile duct and gallbladder has seen notable advancements over the past two decades. With advancements in stent technology, such as the development of lumen-apposing metal stents, and adoption of endoscopic ultrasound and electrosurgical principles in therapeutic endoscopy, what was once considered endoscopic failure has transformed into failure of an approach that could be salvaged by a second- or third-line endoscopic strategy. Incorporation of these advancements in routine patient care will require formal training and multidisciplinary acceptance of established techniques and collaboration for advancement of experimental techniques to generate robust evidence that can be utilized to serve patients to the best of our ability.

Topical sirolimus in dermatology: a systematic review.

CONTEXT: Topical sirolimus is increasingly utilised off-license to manage various dermatological conditions whilst avoiding typical adverse effects associated with systemic sirolimus. However, widespread use is limited by a highly heterogeneous evidence base of mixed quality. OBJECTIVE: to evaluate the current evidence base for the indications, efficacy and safety profile for topical sirolimus in dermatology. DATA SOURCES: A literature search was conducted from 2005 to July 4th, 2023, of English language studies, with the following databases consulted: MEDLINE, PubMed, Embase, CENTRAL and EBSCO. Key words included 'topical', 'rapamycin', 'sirolimus' and 'dermatology'. DATA EXTRACTION: Data on drug efficacy, concentration, side effects, co-interventions and follow up were extracted. RESULTS: The search identified 202 studies; 71 studies met the inclusion criteria. Efficacy of topical sirolimus was demonstrated in facial angiofibromas (799 patients) compared to placebo across multiple randomised controlled trials with a predominant concentration of 0.1%. Evidence was mixed for sirolimus use in port-wine stains (61 patients), with evidence of effectiveness in combined sirolimus and pulsed-dye laser. Multiple case reports demonstrated clinical improvement with topical sirolimus use in cutaneous vascular abnormalities (33 patients) at a higher concentration of 1%. Other applications of topical sirolimus were predominantly case reports demonstrating generally favourable outcomes. Topical sirolimus was generally well tolerated - most reported adverse effects were localised irritation and pruritus. Ointment-based preparations and once-daily dosing appeared to confer a better side effect profile. CONCLUSION: Most high-quality data pertain to the efficacy of topical sirolimus in treating facial angiofibromas in tuberous sclerosis. Outcomes are generally promising in other indications and good tolerability, but data quality is mixed.

The Impact of Intraoperative Glucagon on the Diagnostic Accuracy of Intraoperative Cholangiogram for the Diagnosis of Choledocholithiasis: Experience from a Large Tertiary Care Center.

A proportion of patients who undergo intraoperative cholangiogram (IOC) do not have bile duct stones at the time of endoscopic retrograde cholangiopancreatography (ERCP), either due to the spontaneous passage of stones or a false-positive IOC. Glucagon has been utilized as an inexpensive tool to allow the passage of micro-choledocholithiasis to the duodenum and resolve filling defects caused by stones or air bubbles. The purpose of our study is to understand the change in diagnostic accuracy of IOC to detect choledocholithiasis with intraoperative glucagon. We conducted a retrospective study at a tertiary care center on adult patients who underwent laparoscopic cholecystectomy with IOC. The diagnostic accuracy of IOC was assessed before and after the administration of intravenous glucagon. Of 1455 patients, 374 (25.7%) received intraoperative glucagon, and 103 of these 374 patients (27.5%) showed resolution of the filling defect with the passage of contrast to the duodenum. Pre- and post-glucagon administration comparison showed enhancement in specificity from 78% to 83%, an increase in positive predictive value from 67.3% to 72.4%, and an improvement in the diagnostic accuracy of IOC from 81.5% to 84.3%. Our findings suggest that intraoperative glucagon administration carries the potential to reduce the rate of false-positive IOCs, thereby reducing the performance of unnecessary ERCPs.

Formulation Development of Meloxicam Binary Ethosomal Hydrogel for Topical Delivery: In Vitro and In Vivo Assessment.

The article aimed to formulate an MLX binary ethosome hydrogel for topical delivery to escalate MLX solubility, facilitate dermal permeation, avoid systemic adverse events, and compare the permeation flux and efficacy with the classical type. MLX ethosomes were prepared using the hot method according to the Box-Behnken experimental design. The formulation was implemented according to 16 design formulas with four center points. Independent variables were (soya lecithin, ethanol, and propylene glycol concentrations) and dependent variables (vesicle size, dispersity index, encapsulation efficiency, and zeta potential). The design suggested the optimized formula (MLX-Ethos-OF) with the highest desirability to perform the best responses formulated and validated. It demonstrates a 169 nm vesicle size, 0.2 dispersity index, 83.1 EE%, and -42.76 mV good zeta potential. MLX-Ethos-OF shows an amorphous form in PXRD and a high in vitro drug release of >90% over 7 h by diffusion and erosion mechanism. MLX-Ethos-OF hyaluronic acid hydrogel was fabricated and assessed. It shows an elegant physical appearance, shear thinning system rheological behavior, good spreadability, and skin-applicable pH value. The ex vivo permeation profile shows a flux rate of 70.45 µg/cm2/h over 12 h. The in vivo anti-inflammatory effect was 53.2% ± 1.3 over 5 h. compared with a 10.42 flux rate and 43% inflammatory inhibition of the classical ethosomal type. The conclusion is that binary ethosome is highly efficient for MLX local delivery rather than classical type.

Gaining exposure on perceptions of sunscreen: a national survey of melanoma patients.

Melanoma incidence is increasing. We ascertained perceptions regarding sunscreen and factors influencing choice in patients with melanoma. A survey was distributed to all the supporters of a melanoma patient support group. 571 responses were received across six weeks. Most (79.2%; n=452) indicated they knew how much sunscreen to apply; the most popular frequency of application was once daily (32%, n=180). The most popular cosmetic benefit respondents indicated was reduced redness on sun-exposed areas of skin (73.2%; n=418). Most (96.7%; n=552) agreed more education is needed regarding importance of wearing sunscreen. The three most popular factors in influencing sunscreen choice were SPF more than 50 (n=299; 52.4%), recommendation by a dermatologist (n=267; 46.8%) and price (n=262; 45.9%). Sustainable package design (n=45; 7.9%) and ethical sourcing of ingredients (n=65; 11.4%) were not ranked highly. Given 42% (n=240) only applied sunscreen during sunshine, an education campaign is required. Industry should consider public education regarding sustainability. A further study ascertaining views and perceptions of sunscreen in the non-melanoma cohort is strongly encouraged.

Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.

Prevalence and correlates of paediatric guideline non-adherence for initial empirical care in six low and middle-income settings: a hospital-based cross-sectional study.

OBJECTIVES: This study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings. DESIGN AND SETTING: We used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries. PARTICIPANTS: A total of 2796 children aged 2-23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study. PRIMARY OUTCOME MEASURES: We identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations. RESULTS: Fully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted. CONCLUSIONS: Non-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations.

Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families.

BACKGROUND: Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders. METHODOLOGY AND RESULTS: This current study aims to unwind the molecular etiology of SCID and also extended the patients' phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs*24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191*) gene. CONCLUSION: To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID.

Mucosal Immunity to Poliovirus in Children 0-15 Years of Age: A Community-Based Study in Karachi, Pakistan in 2019.

This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and prevention of poliovirus circulation. A community-based study was conducted in periurban Karachi, Pakistan. Randomly selected children (0-15 years of age) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. Eighty-one of 589 (14%) children excreted PV1 7 days post-OPV challenge; 70 of 81 (86%) were seropositive at baseline. Twelve of 610 (2%) were asymptomatic wild poliovirus type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community.