The Florida Clinical Skills Collaborative: A New Regional Consortium for the Assessment of Clinical Skills.

Discontinuation of the United States Medical Licensing Examination (USMLE) Step 2 Clinical Skills (CS) exam and Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Level 2 Performance Evaluation (2-PE) raised questions about the ability of medical schools to ensure the clinical skills competence of graduating students. In February 2021, representatives from all Florida, United States, allopathic and osteopathic schools initiated a collaboration to address this critically important issue in the evolving landscape of medical education. A 5-point Likert scale survey of all members (n=18/20 individuals representing 10/10 institutions) reveals that initial interest in joining the collaboration was high among both individuals (mean 4.78, SD 0.43) and institutions (mean 4.69, SD 0.48). Most individuals (mean 4.78, SD 0.55) and institutions (mean 4.53, SD 0.72) are highly satisfied with their decision to join. Members most commonly cited a "desire to establish a shared assessment in place of Step 2 CS/2-PE" as their most important reason for joining. Experienced benefits of membership were ranked as the following: 1) Networking, 2) Shared resources for curriculum implementation, 3) Scholarship, and 4) Work towards a shared assessment in place of Step 2 CS/2-PE. Challenges of membership were ranked as the following: 1) Logistics such as scheduling and technology, 2) Agreement on common goals, 3) Total time commitment, and 4) Large group size. Members cited the "administration of a joint assessment pilot" as the highest priority for the coming year. Florida has successfully launched a regional consortium for the assessment of clinical skills competency with high levels of member satisfaction which may serve as a model for future regional consortia.

How to increase chlamydia testing in primary care: a qualitative exploration with young people and application of a meta-theoretical model.

OBJECTIVE: The objective of this study was to explore young people's perspectives barriers to chlamydia testing in general practice and potential intervention functions and implementation strategies to overcome identified barriers, using a meta-theoretical framework (the Behaviour Change Wheel (BCW)). METHODS: Twenty-eight semistructured individual interviews were conducted with 16-24 year olds from across the UK. Purposive and convenience sampling methods were used (eg, youth organisations, charities, online platforms and chain-referrals). An inductive thematic analysis was first conducted, followed by thematic categorisation using the BCW. RESULTS: Participants identified several barriers to testing: conducting self-sampling inaccurately (physical capability); lack of information and awareness (psychological capability); testing not seen as a priority and perceived low risk (reflective motivation); embarrassment, fear and guilt (automatic motivation); the UK primary care context and location of toilets (physical opportunity) and stigma (social opportunity). Potential intervention functions raised by participants included education (eg, increase awareness of chlamydia); persuasion (eg, use of imagery/data to alter beliefs); environmental restructuring (eg, alternative sampling methods) and modelling (eg, credible sources such as celebrities). Potential implementation strategies and policy categories discussed were communication and marketing (eg, social media); service provision (eg, introduction of a young person's health-check) and guidelines (eg, standard questions for healthcare providers). CONCLUSIONS: The BCW provided a useful framework for conceptually exploring the wide range of barriers to testing identified and possible intervention functions and policy categories to overcome said barriers. While greater education and awareness and expanded opportunities for testing were considered important, this alone will not bring about dramatic increases in testing. A societal and structural shift towards the normalisation of chlamydia testing is needed, alongside approaches which recognise the heterogeneity of this population. To ensure optimal and inclusive healthcare, researchers, clinicians and policy makers alike must consider patient diversity and the wider health issues affecting all young people.

Comparison of Five-Year Survival Rate Between Black and White Children With Acute Lymphoblastic Leukemia.

Introduction Despite improvements in the prognosis of acute lymphoblastic leukemia (ALL), it is still the most common childhood cancer. The goal of this study was to investigate if there was a significant difference in the five-year survival between Black and White children with ALL, specifically up to the year 2016 which has not been researched. Methods A retrospective cohort study of Black and White children diagnosed with ALL between 1975 and 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Program database. Children aged 0-19 were separated into Black or White, and then survival analysis was used to compare five-year survival. A multivariate cox regression analysis was carried out to determine the association between race and five-year survival with ALL. Results Our sample included 17,663 cases consisting of 16,238 White children and 1,425 Black children. White children had a significantly increased five-year mortality survival when compared to Black children. Upon using multivariate cox regression analysis, both unadjusted and adjusted models showed a significantly higher risk of death in Black children when compared to White children. Conclusions Our study found that there is a significant difference in the five-year survival between Black and White children diagnosed with ALL. The difference in survival persists even when controlling for sex, age at diagnosis, year of diagnosis, and histology. Future studies should be carried out to control for more confounders that the SEER database is unable to control for.

Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections.

Bacterial sexually transmitted infections (STIs) have been increasing over the past 2 decades in gay, bisexual, and other men who have sex with men. With the widespread use of early human immunodeficiency virus (HIV) treatment, which virtually eliminates transmission risk, and the availability of HIV pre-exposure prophylaxis, there have been attitudinal changes regarding HIV infection with resultant increases in sexual contact and declines in condom use. Doxycycline is used for primary prophylaxis in a number of infectious diseases. We conducted a state-of-the-art review to examine the current state of research, knowledge gaps, and challenges around the use of doxycycline prophylaxis to prevent syphilis and other STIs. International academic and government experts met in March 2019 to frame the initial inquiry, which was supplemented by focused literature searches. Two small short-term randomized controlled trials examining doxycycline prophylaxis found high efficacy. Five additional clinical studies are underway or in development. Studies differed in design, population, outcomes, and safety measures. Doxycycline prophylaxis for bacterial STIs shows promise. Better and more robust data are needed on efficacy; target population; community acceptability; behavioral risk compensation; doxycycline dose, regimen, and formulation; long-term safety; antimicrobial resistance; cost-effectiveness; and risk-benefit.

A Systematic Literature Review of Reviews on the Effectiveness of Chlamydia Testing.

Chlamydia trachomatis is the most common bacterial sexually transmitted infection, causing significant morbidity and economic burden. Strategies like national screening programs or home-testing kits were introduced in some developed countries, yet their effectiveness remains controversial. In this systematic review, we examined reviews of chlamydia screening interventions to assess their effectiveness and the elements that contribute to their success to guide public policy and future research. We assessed English material published after 2000 in PubMed, the Cochrane Library, the British Nursing Index, Medical Database, and Sociological Abstracts, in addition to World Health Organization Global Health Sector Strategies, the European Center for Disease Prevention and Control guidelines, and the Prospective Register of Systematic Reviews. Systematic reviews that focused on chlamydia screening interventions were included. Using the socioecological model, we examined the levels of interventions that may affect the uptake of chlamydia screening. A total of 19 systematic reviews were included. Self-collection in home-testing kits significantly increased screening among girls and women 14-50 years of age. At the organizational level, using electronic health records and not creating additional costs facilitated testing. At the community level, outreach interventions in community and parent centers and homeless shelters achieved high screening rates. At the policy level, interventions with educational and advisory elements could result in significant improvements in screening rates.

Economic evaluation of the cost of different methods of retesting chlamydia positive individuals in England.

OBJECTIVES: The National Chlamydia Screening Programme (NCSP) in England opportunistically screens eligible individuals for chlamydia infection. Retesting is recommended three3 months after treatment following a positive test result, but no guidance is given on how local areas should recall individuals for retesting. Here , we compare cost estimates for different recall methods to inform the optimal delivery of retesting programmes. DESIGN: Economic evaluation. SETTING: England. METHODS: We estimated the cost of chlamydia retesting for each of the six most commonly used recall methods in 2014 based on existing cost estimates of a chlamydia screen. Proportions accepting retesting, opting for retesting by post, returning postal testing kits and retesting positive were informed by 2014 NCSP audit data. Health professionals 'sense-checked' the costs. PRIMARY AND SECONDARY OUTCOMES: Cost and adjusted cost per chlamydia retest; cost and adjusted cost per chlamydia retest positive. RESULTS: We estimated the cost of the chlamydia retest pathway, including treatment/follow-up call, to be between £45 and £70 per completed test. At the lower end, this compared favourably to the cost of a clinic-based screen. Cost per retest positive was £389-£607. After adjusting for incomplete uptake, and non-return of postal kits, the cost rose to £109-£289 per completed test (cost per retest positive: £946-£2,506). The most economical method in terms of adjusted cost per retest was no active recall as gains in retest rates with active recall did not outweigh the higher cost. Nurse-led client contact by phone was particularly uneconomical, as was sending out postal testing kits automatically. CONCLUSIONS: Retesting without active recall is more economical than more intensive methods such as recalling by phone and automatically sending out postal kits. If sending a short message service (SMS) could be automated, this could be the most economical way of delivering retesting. However, patient choice and local accessibility of services should be taken into consideration in planning.

Application of the COM-B model to barriers and facilitators to chlamydia testing in general practice for young people and primary care practitioners: a systematic review.

BACKGROUND: Chlamydia is a major public health concern, with high economic and social costs. In 2016, there were over 200,000 chlamydia diagnoses made in England. The highest prevalence rates are found among young people. Although annual testing for sexually active young people is recommended, many do not receive testing. General practice is one ideal setting for testing, yet attempts to increase testing in this setting have been disappointing. The Capability, Opportunity, and Motivation Model of Behaviour (COM-B model) may help improve understanding of the underpinnings of chlamydia testing. The aim of this systematic review was to (1) identify barriers and facilitators to chlamydia testing for young people and primary care practitioners in general practice and (2) map facilitators and barriers onto the COM-B model. METHODS: Qualitative, quantitative, and mixed methods studies published after 2000 were included. Seven databases were searched to identify peer-reviewed publications which examined barriers and facilitators to chlamydia testing in general practice. The quality of included studies was assessed using the Critical Appraisal Skills Programme. Data (i.e., participant quotations, theme descriptions, and survey results) regarding study design and key findings were extracted. The data was first analysed using thematic analysis, following this, the resultant factors were mapped onto the COM-B model components. All findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Four hundred eleven papers were identified; 39 met the inclusion criteria. Barriers and facilitators were identified at the patient (e.g., knowledge), provider (e.g., time constraints), and service level (e.g., practice nurses). Factors were categorised into the subcomponents of the model: physical capability (e.g., practice nurse involvement), psychological capability (e.g.: lack of knowledge), reflective motivation (e.g., beliefs regarding perceived risk), automatic motivation (e.g., embarrassment and shame), physical opportunity (e.g., time constraints), social opportunity (e.g., stigma). CONCLUSIONS: This systematic review provides a synthesis of the literature which acknowledges factors across multiple levels and components. The COM-B model provided the framework for understanding the complexity of chlamydia testing behaviour. While we cannot at this juncture state which component represents the most salient influence on chlamydia testing, across all three levels, multiple barriers and facilitators were identified relating psychological capability and physical and social opportunity. Implementation should focus on (1) normalisation, (2) communication, (3) infection-specific information, and (4) mode of testing. In order to increase chlamydia testing in general practice, a multifaceted theory- and evidence-based approach is needed. TRIAL REGISTRATION: PROSPERO CRD42016041786.

Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.

OBJECTIVES: Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI). DESIGN: Systematic review and four meta-analyses conducted using random-effects modelling. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017. ELIGIBILITY CRITERIA: Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics. RESULTS: Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10). CONCLUSIONS: High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women.

Facilitators and barriers to chlamydia testing in general practice for young people using a theoretical model (COM-B): a systematic review protocol.

INTRODUCTION: Chlamydia is a key health concern with high economic and social costs. There were over 200 000 chlamydia diagnoses made in England in 2015. The burden of chlamydia is greatest among young people where the highest prevalence rates are found. Annual testing for sexually active young people is recommended; however, many of those at risk do not receive testing. General practice has been identified as an ideal setting for testing, yet efforts to increase testing in this setting have not been effective. One theoretical model which may provide insight into the underpinnings of chlamydia testing is the Capability, Opportunity and Motivation Model of Behaviour (COM-B model). The aim of this systematic review is to: (1) identify barriers and facilitators to chlamydia testing for young people in general practice and (2) use a theoretical model to conduct a behavioural analysis of chlamydia testing behaviour. METHODS AND ANALYSIS: Qualitative, quantitative and mixed methods studies published after 2000 will be included. Seven databases (MEDLINE, PubMed, EMBASE, Informit, PsycInfo, Scopus, Web of Science) will be searched to identify peer-reviewed publications which examined barriers and facilitators to chlamydia testing in general practice. Risk of bias will be assessed using the Critical Appraisal Skills Programme. Data regarding study design and key findings will be extracted. The data will be analysed using thematic analysis and the resultant factors will be mapped onto the COM-B model components. All findings will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: Ethical approval is not required. The results will be disseminated via submission for publication to a peer-review journal when complete and for presentation at national and international conferences. The review findings will be used to inform the development of interventions to facilitate effective and efficient chlamydia testing in general practice.

Examining the potential public health benefit of offering STI testing to men in amateur football clubs: evidence from cross-sectional surveys.

BACKGROUND: In Britain, young people continue to bear the burden of sexually transmitted infections (STIs) so efforts are required, especially among men, to encourage STI testing. The SPORTSMART study trialled an intervention that sought to achieve this by offering chlamydia and gonorrhoea test-kits to men attending amateur football clubs between October and December 2012. With football the highest participation team sport among men in England, this paper examines the potential public health benefit of offering STI testing to men in this setting by assessing their sociodemographic characteristics, sexual behaviours, and healthcare behaviour and comparing them to men in the general population. METHODS: Data were collected from 192 (male) members of 6 football clubs in London, United Kingdom, aged 18-44 years via a 20-item pen-and-paper self-completion questionnaire administered 2 weeks after the intervention. These were compared to data collected from 409 men of a similar age who were resident in London when interviewed during 2010-2012 for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability survey that used computer-assisted-personal-interviewing with computer-assisted-self-interview. Age standardisation and multivariable regression were used to account for sociodemographic differences between the surveys. RESULTS: Relative to men in the general population, SPORTSMART men were younger (32.8 % vs. 21.7 % aged under 25 y), and more likely to report (all past year) at least 2 sexual partners (adjusted odds ratio, AOR: 3.25, 95 % CI: 2.15-4.92), concurrent partners (AOR: 2.05, 95 % CI: 1.39-3.02), and non-use of condoms (AOR: 2.17, 95 % CI: 1.39-3.41). No difference was observed in STI/HIV risk perception (AOR for reporting "not at all at risk" of STIs: 1.25, 95 % CI: 0.76-2.04; of HIV: AOR: 1.54, 95 % CI: 0.93-2.55), nor in reporting STI testing in the past year (AOR: 0.83, 95 % CI: 0.44-1.54), which was reported by only one in six men. CONCLUSIONS: Relative to young men in the general population, football club members who completed the SPORTSMART survey reported greater sexual risk behaviour but similar STI/HIV risk perception and STI testing history. Offering STI testing in amateur football clubs may therefore widen access to STI testing and health promotion messages for men at higher STI risk, which, given the minority currently testing and the popularity of football in England, should yield both individual and public health benefit.

Evaluation of prophylaxis treatment of Candida in alaryngeal patients with tracheoesophageal voice prostheses.

OBJECTIVES/HYPOTHESIS: The objective of this study was to evaluate the effectiveness of nystatin and Biotène(®) mouthwash Oral Rinse for controlling Candida in total laryngectomy (TL) patients with a tracheosophageal voice prosthesis (TEP) because Biotène(®) mouthwash Oral Rinse is a less costly alternative to nystatin and requires less adherence time. STUDY DESIGN: Randomized, unblinded, crossover trial. METHODS: Twenty-one TL patients were randomized to receive nystatin followed by Biotène(®) mouthwash Oral Rinse, or the reverse order, after a basic oral-care phase (i.e., brushing teeth, cleaning dentures). A Provox(®) 2, 22.5 French TEP, which is an indwelling silicone voice prosthesis, was placed at the beginning of each phase. Patients were provided with oral care instructions at randomization and medication-specific instructions with each treatment's initiation. TEPs were processed and evaluated for Candida growth as colony-forming units (CFUs). Wilcoxon signed-rank tests were used for comparisons between treatments. RESULTS: Fifteen patients were available for comparisons of Candida counts (6 received nystatin; 9 received Biotène(®) mouthwash first). Overall, the median log10 (CFUs) remained high regardless of treatment (no medication: 8.9; nystatin: 8.7; Biotène(®) mouthwash: 8.4). However, the median counts for both nystatin and Biotène(®) mouthwash Oral Rinse were lower than those for no medication (difference [Δ]:-0.9 and -0.3, respectively), although only nystatin was significantly lower (P = 0.02). There was no significant difference between the two treatments (P = 0.22). Overall, median medication-adherence was high (97%), and Biotène(®) mouthwash adherence was significantly higher than that of nystatin (Δ: 7.6%; P = 0.03). CONCLUSION: Nystatin and Biotène(®) mouthwash Oral Rinse had similar CFU levels, with nystatin showing a significant improvement over usual oral care. Biotène(®) mouthwash is a less costly alternative to nystatin, with a less complex treatment protocol that might make it preferable to patients and clinicians. LEVEL OF EVIDENCE: 1b

Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial.

BACKGROUND: The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. METHODS: A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. RESULTS: There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. CONCLUSIONS: Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated.

Neck dissection through a facelift incision.

OBJECTIVES/HYPOTHESIS: To determine the feasibility and safety of neck dissection through a facelift incision. STUDY DESIGN: Prospective case series. METHODS: Cadavers and live subjects underwent neck dissection using a facelift incision with and without endoscopic assistance. In the live facelift neck dissection (FLND), the preoperative surgical indications, staging, adjuvant therapy, intraoperative technical procedure, pathology reports on lymph nodes, and short-term outcomes were reviewed. RESULTS: FLND was successfully performed in four cadavers and four live subjects, including selective (less than five neck levels removed) and comprehensive (levels I-V removed) neck dissections. All levels were accessible through this approach, with additional retraction required for levels I and IV. Endoscopic assistance was required in one neck dissection for adequate visualization. Short-term complications and number of excised lymph nodes were comparable to those from traditional neck dissection approaches. CONCLUSIONS: Open neck dissection through a facelift incision is feasible and offers an alternate approach to traditional incisions. This can be performed without requiring robotic assistance and with endoscopic assistance only in certain cases. Endoscopic assistance can offer enhanced visualization of the surgical field and complement open direct approaches in neck dissection. Although FLND offers improved cosmetic outcomes when compared to those of traditional neck incisions, further study is required to determine its efficacy and indications.

Robotic-assisted neck dissection through a pre- and post-auricular hairline incision: preclinical study.

The introduction of robotics in head and neck surgery has facilitated access to the contents of the neck region using less cosmetically obtrusive incisions. Robotic systems offer a three-dimensional viewing, tremor filtration, and articulating distal arms that mimic natural hand and wrist movements. We hypothesized that these characteristics would allow for the performance of a robotic-assisted selective and comprehensive neck dissection via combined pre- and post-auricular incisions. We were able to demonstrate adequate access in a cadaver, using a combination of conventional, endoscopic, and robotic surgical manipulation. Thus preclinical cadaver studies support the ability to perform robotic-assisted neck dissection via combined pre- and post-auricular incisions.

Where do young men want to access STI screening? A stratified random probability sample survey of young men in Great Britain.

OBJECTIVES: Rates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport. METHODS: A stratified random probability survey of 411 (weighted n=632) men in Great Britain aged 18-35 years using computer-assisted personal and self-interviews. RESULTS: Young men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%). CONCLUSIONS: Healthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.

Transoral robotic surgery of the vocal cord.

The standard endoscopic surgical approach in the management of laryngeal lesions is by the use of a laryngoscope, microscope, and laser. This requires the surgeon to work within the confines of the laryngoscope. At times, it requires repositioning of the laryngoscope and microscope to gain access to a specific area. The surgery also requires line-of-sight observation to complete the operation. The introduction of transoral robotic surgery in head and neck surgery brings the advantages of three-dimensional magnification, increased degrees of freedom with the effector arms, and an articulating distal end that mimics hand movements. To date, transoral robotic surgery of vocal cord surgery requires the use of a tracheostomy in patients. Here we report the use of a CO(2) laser fiber and the Da Vinci robotic platform (Intuitive Surgical) for the surgical management of a T1 glottic squamous cell carcinoma.