Basal cell carcinoma (BCC) is a significant public health concern, with more than 3 million cases occurring each year in the United States, and with an increasing incidence. The molecular basis of ...BCC is complex, involving an interplay of inherited genetic susceptibility, including single nucleotide polymorphisms and genetic syndromes, and sporadic somatic mutations, often induced by carcinogenic exposure to UV radiation. This review outlines the currently known germline and somatic mutations implicated in the pathogenesis of BCC, including the key molecular pathways affected by these mutations, which drive oncogenesis. With advances in next generation sequencing and our understanding of the molecular genetics of BCC, established and emerging targeted therapeutics are offering new avenues for the non-surgical treatment of BCC. These agents, including Hedgehog pathway inhibitors, immune modulators, and histone deacetylase inhibitors, will also be discussed.
Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic stem cell transplantation. These patients face unique challenges due to the complexity of GVHD ...which can affect multiple organ systems, and the toxicity of treatments. Despite the known impact on quality of life (QOL), qualitative data within the bone marrow transplantation (BMT) literature is rare, and there has been no qualitative work exploring patient experience of specialist healthcare provision for GVHD in the United Kingdom.
We conducted a primary explorative qualitative study of the experience of QOL issues and multidisciplinary care in patients with chronic GVHD following allogeneic stem cell transplantation. Eight patients were identified using convenience sampling from specialist BMT outpatient clinics. Following consent, patients were interviewed individually via telephone. Transcripts of interviews were analyzed using an inductive thematic approach.
Mean participant age was 61-years-old (range 45-68), with a mean time post-transplant of 3 years at time of interview (range 3 months-15 years). Five key QOL themes were identified: (1) 'Restricted as to what I can do'; (2) Troubling symptoms-'you can sort of get GVHD anywhere'; (3) Confusion/uncertainty over GVHD symptoms-'Is this the GVHD?'; (4) Unpredictable course and uncertainty about the future; and (5) Adapting to the sick role. In addition, four themes related to experience of service provision were identified: (1) personal care and close relationship with BMT nurses; (2) efficiency versus long waits-'On the case straight away'; (3) information provision-'went into it with a bit of a rosy view'; and (4) the role of support groups.
These qualitative data reflect the heterogeneity of experiences of the GVHD patient population, reflecting the need for a flexible and nuanced approach to patient care with emphasis on comprehensive information provision. We have identified the key role that BMT specialist nurses within the multidisciplinary team play in supporting patients. We advocate future research should focus on ways to meet the complex needs of this patient group and ensure that the personal care and close relationships are not lost in service redesigns embracing remote consultations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In UK medical schools, five-option single-best answer (SBA) questions are the most widely accepted format of summative knowledge assessment. However, writing SBA questions with four effective ...incorrect options is difficult and time consuming, and consequently, many SBAs contain a high frequency of implausible distractors. Previous research has suggested that fewer than five-options could hence be used for assessment, without deterioration in quality. Despite an existing body of empirical research in this area however, evidence from undergraduate medical education is sparse. The study investigated the frequency of non-functioning distractors in a sample of 480 summative SBA questions at Cardiff University. Distractor functionality was analysed, and then various question models were tested to investigate the impact of reducing the number of distractors per question on examination difficulty, reliability, discrimination and pass rates. A survey questionnaire was additionally administered to 108 students (33 % response rate) to gain insight into their perceptions of these models. The simulation of various exam models revealed that, for four and three-option SBA models, pass rates, reliability, and mean item discrimination remained relatively constant. The average percentage mark however consistently increased by 1–3 % with the four and three-option models, respectively. The questionnaire survey revealed that the student body had mixed views towards the proposed format change. This study is one of the first to comprehensively investigate distractor performance in SBA examinations in undergraduate medical education. It provides evidence to suggest that using three-option SBA questions would maximise efficiency whilst maintaining, or possibly improving, psychometric quality, through allowing a greater number of questions per exam paper.
Phenomenon: Problem-based learning (PBL) and other small-group, active learning methodologies have been widely adopted into undergraduate and postgraduate healthcare curricula across the world. ...Although much research has examined student perceptions of these innovative teaching pedagogies, there are still questions over which factors influence these views. This article aims to identify these key elements that affect healthcare student satisfaction with PBL and other small-group learning methods, including case-based and team-based learning. Approach: A systematic rapid review method was used to identify high-quality original research papers from the healthcare education literature from between 2009 and 2014. All papers were critically appraised before inclusion in line with published guidelines. Narrative synthesis was achieved using an inductively developed, thematic framework approach. Findings: Fifty-four papers were included in the narrative synthesis. The evidence suggests that, despite an initial period of negative emotion and anxiety, the perspectives of healthcare students toward small-group, active learning methods are generally positive. The key factors influencing this satisfaction level include (a) the facilitator role, (b) tutorial structure, (c) individual student factors, (d) case authenticity, (e) increased feedback, (f) group harmony, and (g) resource availability. Insights: Student satisfaction is an important determinant of healthcare education quality, and the findings of this review may be of value in future curriculum design. The evidence described here suggests that an ideal curriculum may be based on an expert-led, hybrid PBL model.
Hidradenitis suppurativa (HS) is known to disproportionately affect patients of color; however, there is a paucity of evidence on how its disease profile varies between races and ethnic groups.
...Explore potential race-dependent differences in the disease profile of HS.
A retrospective analysis was conducted on HS patients at Stanford Hospital and Clinics. Data were compared in terms of demographics, disease severity, and healthcare utilization between races in adults identified to have at least 2 encounters coded for HS. Validation was conducted using Optum's de-identified Clinformatics Data Mart Database of national insurance claims.
Our cohorts consisted of 939 HS patients seen at Stanford and 13,885 HS patients taken from the national dataset. Black and Hispanic patients had greater healthcare utilization compared to White patients. In addition, Hispanic patients at our institution also had significantly increased disease severity compared to their White counterparts (χ2P = .009). Hispanic patients entered tertiary care at an earlier age (Stanford mean: 30.8 years for Hispanics vs 38.7 for Whites; P < .001), while Black patients entered later (Stanford mean: 39.6 years).
These cohorts may not be representative of the entire HS patient population.
Our findings suggest that patients of color may have greater healthcare utilization and disease severity compared to other groups.
The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously ...conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC.
We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed.
Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% 90% confidence interval (CI), 54%-82.5%. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported.
The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC.
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that ...complicate the disease course. Although these comorbidities have been well described, it remains unclear how these comorbidities coassociate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and sex. In this comprehensive analysis of 77 million patients in a large US population-based cohort, we examined coassociation patterns among HS comorbidities and identified clinically relevant phenotypic subtypes within HS. We demonstrated that these subtypes not only differed among races, but also influenced clinical outcomes as measured by HS-related emergency department visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by patients with HS and equip clinicians with a framework for risk stratification and improved targeted care in HS.
•This systematic review used the COSMIN methodology to identify PROMs for use in GVHD.•Twenty-seven PROMs were identified with varying levels of supportive psychometric evidence.•Three PROMs had ...evidence to support reliability, responsiveness, and validity for chronic GVHD.•Few PROMs had psychometric validation for acute GVHD.•Future research should include comprehensive psychometric testing of PROMs for GVHD.
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. These patients face a unique challenge due to the complexity of GVHD and the toxicity of treatments received. GVHD has significant impact on quality of life (QOL), but this is not routinely evaluated formally. Despite the availability of patient-reported outcome measures (PROMs) to assess QOL, there is currently no consensus regarding the optimal PROMs that should be used to evaluate the impact of GVHD. We undertook a systematic review to determine the current evidence for the use of PROMs in assessment of QOL, symptom burden, and disease severity of patients with GVHD. A comprehensive systematic review based on the COSMIN guidelines was conducted to identify studies using PROMs (including those for QOL and symptom burden) in acute and chronic GVHD (cGVHD) patients. The following databases were searched: OVID Medline, AMED, CINAHL, Embase, PROQOLID, ProQuest, PsychINFO, and Social Sciences Citation Index from inception to May 2018. Hand searches updated the search to December 2018. Articles were screened by 2 independent reviewers, with discrepancies resolved by a third independent reviewer. Included articles were critically appraised using the COSMIN Risk of Bias tool, and relevant data on measurement properties for the included PROMs were extracted from within the target population. A total of 4545 articles were identified, and 64 articles reporting on 27 PROMs were included in this review. PROMs were separated into 5 groups; generic patient-reported measures (n = 7), cancer-specific measures (n = 4), bone marrow transplant–specific measures (n = 2), cGVHD-specific measures (n = 4), and dimension-specific measures (n = 10). Three PROMs (Human Activity Profile, Lee Symptom Scale, National Institutes of Health Eleven Point Scale) had evidence to support strong reliability (including internal consistency), responsiveness, and aspects of validity within the cGVHD population. Only 5 included PROMs were used in patients with acute GVHD. This review summarizes the current evidence regarding the use of 27 included PROMs in the context of GVHD. The choice of the most optimal PROM depends on the clinical or research context of use. Future research should comprehensively validate these tools in the GVHD population, including the testing and possible development of a PROM for use in acute GVHD, which remains a current critical gap in the existing literature.
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