Assessment of diversity in skin colour in dermatology medical education resources.

One hundred and fifty-three patient images from the general resources and 3583 images from Dermatology were evaluated. The majority of images were Fitzpatrick Type II (54%), followed by Type III (27%). Our findings demonstrate the lack of skin diversity continues across many medical school resources, with fair skin (Fitzpatrick Type II) accounting for the majority of images.

Barriers and enablers to participating in regular screening programmes for women with cerebral palsy: A qualitative life course study.

AIMS: To determine the barriers and enablers to regular, women-oriented screening programmes for women with cerebral palsy (CP); and to discuss the participants' suggestions for change. DESIGN: Qualitative life course approach. METHODS: Twenty-five life course interviews were conducted with women in 2020 who identified as having a diagnosis of CP. Interviews were conducted in person or using electronic platforms. Framework analysis was used to interpret the data. FINDINGS: Access and utilization of regular screening programmes for women with CP across the life course are determined by multiple socioecological factors. Three themes are discussed focusing particularly on cervical and breast screening: 1. barriers, 2. enablers and 3. women's suggestions for change. Some women chose to opt out of sexual health checks for fear they would be too uncomfortable or the procedure would be too difficult. Practitioner attitudes towards disability in general, as well as the extent to which they understood the effects of CP for women, was highlighted as a barrier. Accessibility and adaptability of the environment also influenced women's uptake of screening. CONCLUSION: Women with CP face many challenges to their sexual and reproductive healthcare. These can deter them from participating in regular women-oriented screening programmes, which puts them at higher risk of preventable diseases. Understanding the lifelong effects of CP for women, and the interaction with their reproductive health could help to reduce unmet needs and increase participation in relevant screening across the life course. IMPACT: Knowledge of the challenges to regular screening programmes experienced by women with CP across the life course is crucial to provide appropriate preventative healthcare for women with CP across different stages of life. Elements of this knowledge could have benefits for the care of all disabled women.

Real-world outcomes in locally advanced or metastatic urothelial carcinoma following platinum and PD-1/L1 inhibitor therapy.

Aim: To investigate real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) in locally advanced/metastatic urothelial carcinoma postplatinum and postprogrammed death receptor-1/death ligand 1 inhibitors. Patients & methods: Adult patients diagnosed with locally advanced/metastatic urothelial carcinoma from 1 January 2011 to 31 December 2018 and treated with taxane monotherapy or any therapy postplatinum and post-PD-1/L1 inhibitors were included from a nationwide electronic health record-derived oncology database. Results: Median rwOS among 72 patients treated with taxane monotherapy was 7.6 months (95% CI: 5.2-14.4) and rwPFS was 2.9 months (95% CI: 2.4-4.0). Among 208 patients treated with any therapy, median rwOS was 8.9 months (95% CI: 7.3-10.6) and rwPFS was 3.6 months (95% CI: 2.7-4.7). Conclusion: Short duration of rwOS and rwPFS were observed, highlighting the need for effective and safe treatments in this patient population.

Lay abstract Few studies have evaluated survival outcomes in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy in clinical practice. In this study, we used electronic health records from a nationwide cancer database to assess survival in adult patients who received further treatment in this setting from 2011 to 2018. Among 72 patients who were treated with taxane monotherapy after chemotherapy and a PD-1/L1 inhibitor, average overall survival was 7.6 months and progression-free survival was 2.9 months. Among 208 patients who were treated with any therapy, average overall survival was 8.9 months and progression-free survival was 3.6 months. These results highlight the need for safer and more effective therapies in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy.

Economic Impact of Adherence to Pain Treatment Guidelines in Chronic Pain Patients.

OBJECTIVES: This research compared health care resource use (HCRU) and costs for pharmacotherapy prescribing that was adherent vs nonadherent to published pain management guidelines. Conditions included osteoarthritis (OA) and gout (GT) for nociceptive/inflammatory pain, painful diabetic peripheral neuropathy (pDPN) and post-herpetic neuralgia (PHN) for neuropathic pain, and fibromyalgia (FM) for sensory hypersensitivity pain. METHODS: This retrospective cohort study used claims from MarketScan Commercial and Medicare Databases identifying adults newly diagnosed with OA, GT, pDPN, PHN, or FM during July 1, 2006, to June 30, 2013, with 12-month continuous coverage before and after initial (index) diagnosis. Patients were grouped according to their pharmacotherapy pattern as adherent, nonadherent, or "unsure" according to published pain management guidelines using a claims-based algorithm. Adherent and nonadherent populations were compared descriptively and using multivariate statistical analyses for controlling bias. RESULTS: Final cohort sizes were 441,465 OA, 76,361 GT, 10,645 pDPN, 4,010 PHN, and 150,321 FM, with adherence to guidelines found in 51.1% of OA, 25% of GT, 59.5% of pDPN, 54.9% of PHN, and 33.5% of FM. Adherent cohorts had significantly (P < 0.05) fewer emergency department (ED) visits and lower proportions with hospitalizations or ED visits. Mean health care costs increased following diagnosis across all conditions; however, adherent cohorts had significantly lower increases in adjusted costs pre-index to postindex (OA $5,286 vs $9,532; GT $3,631 vs $7,873; pDPN $9,578 vs $16,337; PHN $2,975 vs $5,146; FM $2,911 vs $3,708; all P < 0.001; adherent vs nonadherent, respectively). CONCLUSIONS: Adherence to pain management guidelines was associated with significantly lower HCRU and costs compared with nonadherence to guidelines.

Soluble tumour necrosis factor receptor type II and survival in colorectal cancer.

BACKGROUND: Chronic inflammation may play a role in colorectal cancer (CRC) pathogenesis. The relationship between soluble tumour necrosis factor receptor type II (sTNF-RII) and survival among CRC patients is not well defined. METHODS: We prospectively evaluated the association between pre-diagnosis plasma levels of sTNF-RII and mortality in 544 CRC patients from the Nurses' Health Study and Health Professionals Follow-Up Study diagnosed from 1990 to 2010. Primary and secondary end points were overall and CRC-specific mortality, respectively. Cox proportional hazards models were used to calculate multivariate hazard ratios for mortality. RESULTS: Higher sTNF-RII levels were significantly associated with increased overall mortality (multivariate HR=1.48, 95% CI 1.02-2.16, P-trend=0.006), but not with CRC-specific mortality (HR=1.23, 95% CI 0.72-2.08, P-trend=0.34). In subgroup analyses, among regular aspirin users, those with higher sTNF-RII levels had an adjusted HR of 0.52 (95% CI 0.20-1.33) for overall mortality compared with those with lower sTNF-RII levels, whereas among nonregular aspirin users the adjusted HR was 2.26 (95% CI 1.23-4.01, P for interaction=0.53). CONCLUSIONS: Among CRC patients, higher sTNF-RII levels are associated with a significant increase in overall mortality, but not CRC-specific mortality. The role of inflammation and anti-inflammatory medications in survival of CRC patients warrants further exploration.

Evaluating Guideline-recommended Pain Medication Use Among Patients with Newly Diagnosed Fibromyalgia.

OBJECTIVES: To compare pain medication treatment changes across cohorts of newly diagnosed patients with fibromyalgia (FM) treated with guideline-recommended medications or opioids. METHODS AND DESIGN: Retrospective claims data analysis examined adult commercial health plan members newly diagnosed with FM (initial diagnosis = index date) from January 2008 to February 2012. Patients had 6-month pre-index and 12-month postindex periods and received pain medication within 6 months postindex; cohorts were based on the first postindex medication. Guideline-recommended medication cohorts were anti-epileptic drug (AED), serotonin-norepinephrine reuptake inhibitor (SNRI), selective serotonin reuptake inhibitor (SSRI), and tricyclic antidepressant (TCA). Short-acting and long-acting opioid (SAO, LAO) cohorts were also identified. Pairwise comparisons with the SAO cohort were conducted. Cox proportional hazards regressions modeled the likelihood of receiving guideline-recommended therapy. RESULTS: The final sample was 96,175 patients (mean age 47.3 years; 72.5% female), distributed into SAO (57%), SSRI (22%), AED (10%), SNRI (6%), TCA (3%), and LAO (2%) cohorts. The SAO cohort had the most discontinuation (49% vs. 6% to 22%, P < 0.01) and the least augmentation (29% vs. 35% to 50%, P < 0.01). Regression analyses indicated that patients with (vs. without) pre-index guideline-recommended medications were 2 to 4 times more likely to receive them postindex. Patients in the opioid cohorts were about half as likely to receive subsequent guideline-recommended medications. CONCLUSIONS: Opioid use was widespread among patients with FM. Once patients received opioids postdiagnosis, the likelihood of receiving guideline-recommended medications was small. These real-world results indicate an opportunity may exist for improved FM management using recommended therapies in clinical practice.

Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis.

Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.

The everydayness of falling: consequences and management for adults with cerebral palsy across the life course.

PURPOSE: To explore the cause, influences and consequences of falling for adults with cerebral palsy (CP) across their life course, and how this is managed. MATERIALS AND METHODS: We used interview data from a multimethod UK study exploring the effects of ageing with CP and healthcare across the life course. Twenty-six participants were recruited and interviewed using various digital platforms to maximise inclusive participation in the UK. Follow-up email semi-structured interviews were conducted to further explore experiences of falls. Transcribed interviews were analysed thematically. RESULTS: Falling and fear of falling (FoF) is problematic for over half of the participants in the sample. They perceived falls and FoF as limiting their participation, autonomy and independence in employment, social and cultural activities. Participants used their own management strategies, due to limited specialist interventions or practitioner knowledge to manage or prevent falls. Practices, such as the use of a wheelchair or avoiding activities prompted changes to relationships and identity. CONCLUSIONS: Falling for adults with CP happens earlier in life compared to the general population. Adults with CP may benefit from specialist falls prevention services to help maintain muscle strength and balance. Research is needed to evaluate effective interventions for people with CP.

Falling negatively impacts on the lives and identities of people with cerebral palsy, including younger adults.In other areas such as services for older people, or those who have experienced stroke, rehabilitation services have helped people reduce falls rates through maintaining strength and balance.Falls prevention rehabilitation services are needed for people with cerebral palsy and should include relevant mobility devices and assistive technologies while maintaining social participation and quality of life.

Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism.

Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.

A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design.

Low-renin hypertension affects 1 in 4 people with hypertension, but the optimal management of this condition is not known. We hypothesize that a large proportion of people with low-renin hypertension is mediated by excess mineralocorticoid receptor (MR) activation and that targeted treatment with an MR antagonist (MRA) will be beneficial. This randomized, single-blinded, titration-to-effect aims to investigate whether targeted treatment in low-renin hypertension with MRA is better compared to standard antihypertensives in terms of blood pressure control and end-organ protection. Adults with hypertension, who are treatment naïve or are receiving up to two antihypertensive agents and have a low direct renin concentration <10 mU/L will be included. Participants with severe hypertension, a secondary cause of hypertension, pregnant, breastfeeding, with moderate-severe cardiovascular and chronic kidney disease, or on medications that confound interpretation of the plasma direct renin or aldosterone concentrations will be excluded. Eligible participants will be randomized 1:1 to either MRA therapy (spironolactone) or standard anti-hypertensive therapy (perindopril+/- amlodipine) for 48 weeks. Anti-hypertensives will be up-titrated every 12 weeks until target blood pressure is achieved. The primary objective will be to determine the total defined daily dose of antihypertensives required to achieve the target blood pressure and change in mean clinic systolic blood pressure at week 48. Current hypertension guidelines do not have specific recommendations for the choice of anti-hypertensive medications for people with low-renin hypertension. The results of this trial could guide future hypertension guidelines.

Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population.

Introduction: Low-renin hypertension is an underrecognized subtype of hypertension with specific treatment options. This study aims to identify the prevalence in primary care and to compare patient characteristics to those with normal-renin hypertension and primary aldosteronism (PA). Methods: In a cohort study, patients with treatment-naïve hypertension were screened for PA with plasma aldosterone and direct renin concentrations. Patients with an elevated aldosterone-to-renin ratio [≥70 pmol/mU (≥2.5 ng/dL:mU/L)] underwent confirmatory testing. All screened patients were then classified as having (1) normal-renin hypertension, (2) low-renin hypertension (direct renin concentration <10mU/L (plasma renin activity ∼<1 ng/mL/hour) and not meeting the criteria for PA), or (3) confirmed PA. Results: Of the 261 patients, 69 (26.4%) had low-renin hypertension, 136 (51.9%) had normal renin hypertension, and 47 (18.0%) had PA. Patients with low-renin hypertension were older and more likely to be female compared to normal-renin hypertension (57.1 ± 12.8 years vs 51.8 ± 14.0 years, P < .05 and 68.1% vs 49.3%, P < .05, respectively) but similar to PA (53.5 ± 11.5 years and 55.3%). However, in an adjusted binomial logistic regression, there was no association between increasing age or sex and low-renin hypertension. The median aldosterone concentration was lower compared to patients with normal-renin hypertension and PA: 279 pmol/L (216-355) vs 320 pmol/L (231-472), P < .05 and 419 pmol/L (360-530), P < .001. Conclusion: At least a quarter of treatment-naïve hypertensive patients in primary care had a low direct renin concentration but did not meet the criteria for PA. Patient characteristics were similar, aside from a lower aldosterone concentration compared to patients with normal-renin hypertension and PA. Further research is needed to understand the underlying pathophysiology of low-renin hypertension and the optimal first-line treatment.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity.

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow-up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31-56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42-55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%-29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%-63%) compared to eyes without APROP (13.4%, 95%CI, 8%-22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Predictors of Matching into Anesthesiology and Surgery: Analysis of One Program's Results.

PURPOSE: The objectives of this study were to use a multivariable regression model to determine what application factors made anesthesiology and surgery applicants more or less likely to match into an anesthesiology or surgery residency program. METHODS: Surgery and Anesthesiology applicants listed on the final National Resident Matching Program (NRMP) Rank Order Lists from WMC in the 2020-2021 application cycle were included in analysis. All applicant data were collected through the Electronic Residency Application Service (ERAS). All ERAS and letters of recommendation (LOR) data were deidentified and LOR were subsequently inputted into a linguistics software to analyze the language use in LOR. Descriptive analyses were conducted to compare variables between applicants that matched to a specific residency program and those who matched elsewhere. A multivariable regression model was then used to determine characteristics of anesthesiology and surgery applicants that were indicative of matching to a specific rank of residency program. RESULTS: A total of 116 anesthesiology and 78 surgery applicants were included in final analysis. Analysis of anesthesiology applicants yielded four significant application characteristics that influenced matching to a higher or lower ranked residency program: USMLE Step 2 CK scores, medical school attended, insight category words in LOR, and anger category words in LOR. Similarly, analysis of surgery applicants yielded four significant characteristics: Race, USMLE Step 1 scores, insight category words, and see category words. CONCLUSION: Our results demonstrated that specialties of anesthesiology and surgery considered different metrics regarding the residency application process. Among the many factors that were analyzed, USMLE scores and language in LOR were considered significant in both specialties. As the application process continues to evolve, we may see a shift in what application factors are considered more important than others.

The impact of ageing on adults with cerebral palsy: the results of a national online survey.

BACKGROUND: Cerebral palsy (CP) is one of the most common neurological disorders in children and results in lifelong physical impairments. Adults with CP have approximately the same life expectancy as their non-disabled peers, so helping them to stay healthy throughout the life course will have long-term cost benefits via reductions in hospital admissions, long-term care, and unemployment rates. AIM: To explore how adults with CP experience ageing. DESIGN & SETTING: National online survey given to adults with CP in the UK. METHOD: The participants were adults with CP. Items for the online survey were taken from existing self-report measures, with additional items developed for the survey. Several domains of functioning were assessed including mobility, dexterity, fatigue, pain, speech, mental health, swallowing and health maintenance/self-care as well as healthcare usage. Data were analysed using χ2 to examine the relationships between the demographic variables and the survey responses. RESULTS: The survey was completed by 395 participants, of whom 74.2% were female and approximately 59.3% aged <45 years. Responders reported having problems with mobility, pain, and fatigue with older participants reporting higher levels of pain and more mobility problems, although the correlations were fairly small. Healthcare usage was surprisingly low. CONCLUSION: The study found that age was associated with a decline in mobility and a higher level of pain, although the relationships were weak. It is possible that the low healthcare usage among the responders is owing to services not being available to respond to their needs.

Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma.

CONTEXT: Allergic asthma continues to increase despite new pharmacological advances for both acute treatment and chronic-disease management. Asthma is a multifactorial disease process with genetic, allergic, infectious, environmental, and dietary origins. Researchers are investigating the benefits of lifestyle changes and alternative asthma treatments, including the ability of bromelain to inhibit inflammation. Bromelain is a commonly used, proteolytically active pineapple extract. OBJECTIVE: The present study intended to determine the ability of bromelain to reduce the inflammation of preexisting asthma via an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). DESIGN: The research team designed a study examining the effects of bromelain in a control group of mice that received phosphate buffered saline (PBS) only and in an intervention group that received bromelain in PBS. Setting The study took place in the Department of Immunology at the University of Connecticut's School of Medicine, Farmington. Intervention The research team sensitized female C57BL/6J mice with intraperitoneal OVA/alum and then challenged them with OVA aerosolization for 10 consecutive days. On day 4, the team began administering daily doses of PBS to the control group (n = 10) and bromelain (6mg/kg) in PBS to the bromelain (intervention) group (n = 10). OUTCOME MEASURES: The primary measures included bronchoalveolar lavage (BAL) cellular differential, cellular phenotype via flow cytometry, and lung histology. Additional outcomes included testing for serum cytokines and immunoglobulin. RESULTS: Bromelain treatment of AAD mice (bromelain group) resulted in significant anti-inflammatory activity as indicated by reduced BAL total leukocytes (P < .05), eosinophils (P < .05), and cellular infiltrates via lung pathology (P < .005), as compared to the control group. In addition, bromelain significantly reduced BAL CD4+ and CD8+ T cells without affecting cell numbers in the spleen or hilar lymph node. The study found decreased interleukins IL-4, IL-12, IL-17, as well as IFN-α in the serum of bromelain-treated animals. CONCLUSIONS: The results suggest that bromelain has a therapeutic effect in established AAD, which may translate into an effective adjunctive therapy in patients with similar conditions, such as allergic asthma, who have chosen to initiate treatment after the onset of symptoms.

An insight into the iPSCs-derived two-dimensional culture and three-dimensional organoid models for neurodegenerative disorders.

The use of induced pluripotent stem cells (iPSCs) is a promising approach when used as models to study neurodegenerative disorders (NDDs) in vitro. iPSCs have been used in in vitro two-dimensional cultures; however, these two-dimensional cultures do not mimic the physiological three-dimensional cellular environment. The use of iPSCs-derived three-dimensional organoids has risen as a powerful alternative to using animal models to study NDDs. These iPSCs-derived three-dimensional organoids can resemble the complexity of the tissue of interest, making it an approachable, cost-effective technique, to study NDDs in an ethical manner. Furthermore, the use of iPSCs-derived organoids will be an important tool to develop new therapeutics and pharmaceutics to treat NDDs. Herein, we will highlight how iPSCs-derived two-dimensional cultures and three-dimensional organoids have been used to study NDDs, as well as the advantages and disadvantages of both techniques.