Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

Masters of the manipulator: two new hypocrealean genera, Niveomyces (Cordycipitaceae) and Torrubiellomyces (Ophiocordycipitaceae), parasitic on the zombie ant fungus Ophiocordyceps camponoti-floridani.

During surveys in central Florida of the zombie-ant fungus Ophiocordyceps camponoti-floridani, which manipulates the behavior of the carpenter ant Camponotus floridanus, two distinct fungal morphotypes were discovered associated with and purportedly parasitic on O. camponoti-floridani. Based on a combination of unique morphology, ecology and phylogenetic placement, we discovered that these morphotypes comprise two novel lineages of fungi. Here, we propose two new genera, Niveomyces and Torrubiellomyces, each including a single species within the families Cordycipitaceae and Ophiocordycipitaceae, respectively. We generated de novo draft genomes for both new species and performed morphological and multi-loci phylogenetic analyses. The macromorphology and incidence of both new species, Niveomyces coronatus and Torrubiellomyces zombiae, suggest that these fungi are mycoparasites since their growth is observed exclusively on O. camponoti-floridani mycelium, stalks and ascomata, causing evident degradation of their fungal hosts. This work provides a starting point for more studies into fungal interactions between mycopathogens and entomopathogens, which have the potential to contribute towards efforts to battle the global rise of plant and animal mycoses. Citation: Araújo JPM, Lebert BM, Vermeulen S, et al. 2022. Masters of the manipulator: two new hypocrealean general, Niveomyces (Cordycipitaceae) and Torrubiellomyces (Ophiocordycipitaceae), parasitic on the zombie ant fungus Ophiocordyceps camponoti-floridani. Persoonia 49: 171-194. https://doi.org/10.3767/persoonia.2022.49.05.

Born on U.S. Soil: Access to Healthcare for Neonates of Non-Citizens.

INTRODUCTION: The 14th amendment of the United States (US) Constitution guarantees citizenship to infants born in the US. With documentation of citizenship, typically through a birth certificate, neonates gain official identity and the opportunity to qualify for services like healthcare. Most guidance on caring for immigrant children assumes that access to health care is guaranteed for babies born in the US. In practice, some infants born to non-citizen mothers face barriers in obtaining services fundamental to neonatal health. METHODS: We conducted a review of the literature to identify articles on access to care for infants born to non-citizen mothers in the US. Because of the scarcity of relevant peer-reviewed published literature on this topic, the search was broadened to grey literature including news articles, online articles, and legal reviews. Using these aggregated sources, we created a framework for understanding maternal immigration status and barriers to healthcare for neonates born in the US. We discuss risk factors from the public health, historical and ethical perspectives. RESULTS: Barriers exist for some mother-infant dyads in obtaining services such as healthcare, health insurance and supplemental nutrition programs. At-risk dyads include neonates of undocumented immigrants and birth tourists as well as neonates born to women on visas. The impact of these barriers on health-seeking behaviors, access to care, and health outcomes for these neonates is largely unknown. DISCUSSION: The framework for understanding challenges of non-citizen mothers and their infants that we present in this article provides a resource for physicians and public health professionals serving this population. That much of the literature exists outside of healthcare highlights the need for more scholarly work on this problem. Future research will better inform advocacy and public health efforts to protect this vulnerable population of newborn citizens and their mothers.

What Attracts Medical Students to Primary Care? A Nominal Group Evaluation.

OBJECTIVE: To examine the perceptions of first-year medical students on their experiences in primary care. METHODS: Nominal group technique sessions were conducted with first-year medical students for 5 years. Questions were designed to evaluate primary care experiences and the role of primary care physicians. The questions explored what would make them consider primary care, what would detract from it, and what primary care has to offer that no other specialty can. Responses were weighted and ranked. The main outcome was the top five responses to three questions that were obtained at each session. RESULTS: Thirty-four students generated 280 responses to 3 questions. The top 5 responses for each year resulted in 29 experiences that strengthen enthusiasm: patient interactions (weighted sum, 43%), physician interactions/role modeling (22%), community interactions (20%), healthcare system/finances (8%), and other (6%). The top 5 responses resulted in 26 experiences that weaken enthusiasm, including hidden curriculum (45%), poor role models (29%), uncertainties about the healthcare system such as finances and documentation (20%), and patient interactions (6%). The top 5 responses regarding the uniqueness of primary care resulted in 37 experiences, including patient interactions (38%), continuity of care (20%), knowledge base (13%), community impact (10%), lifestyle benefits (10%), and education/prevention (9%). CONCLUSIONS: Medical students highlighted unique relationships with patients and continuity of care as experiences that increase their enthusiasm for primary care. Negative experiences that weakened enthusiasm for primary care included hidden curriculum and poor role models. Programs that provide experiences in primary care can increase student interest in primary care careers.

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records.

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management.

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.

BACKGROUND: Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use. METHODOLOGY: Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. RESULTS: Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. CONCLUSIONS: Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

Zombie-ant fungi across continents: 15 new species and new combinations within Ophiocordyceps. I. Myrmecophilous hirsutelloid species.

Ophiocordyceps species infecting ants - the so-called zombie-ant fungi - comprise one of the most intriguing and fascinating relationships between microbes and animals. They are widespread within tropical forests worldwide, with relatively few reports from temperate ecosystems. These pathogens possess the ability to manipulate host behaviour in order to increase their own fitness. Depending on the fungal species involved the infected ants are manipulated either to leave the nest to ascend understorey shrubs, to die biting onto vegetation, or descend from the canopy to die at the base of trees. Experimental evidence has demonstrated that the behavioural change aids spore dispersal and thus increases the chances of infection, because of the existing behavioural immunity expressed inside ant colonies that limits fungal development and transmission. Despite their undoubted importance for ecosystem functioning, these fungal pathogens are still poorly documented, especially regarding their diversity, ecology and evolutionary relationships. Here, we describe 15 new species of Ophiocordyceps with hirsutella-like asexual morphs that exclusively infect ants. These form a monophyletic group that we identified in this study as myrmecophilous hirsutelloid species. We also propose new combinations for species previously described as varieties and provide for the first time important morphological and ecological information. The species proposed herein were collected in Brazil, Colombia, USA, Australia and Japan. All species could readily be separated using classic taxonomic criteria, in particular ascospore and asexual morphology.

Visceral Vistas: Basil Hirschowitz and the Birth of Fiberoptic Endoscopy.

Fiberoptic endoscopy was developed at the University of Michigan in the 1950s by gastroenterology fellow Basil Hirschowitz and 2 physicists. Previous methods to visualize the gastrointestinal lumen used rigid instruments that relied on rudimentary optical systems. They were limited in reach and caused patients considerable discomfort. Fiberoptic technology dramatically changed endoscopic practice. The fiberoptic endoscope, or fiberscope, was a flexible instrument that allowed direct inspection of the gastrointestinal lumen. Although many practicing endoscopists initially resisted its adoption, the fiberscope ultimately held sway. Studying the period from the fiberscope's first introduction in the late 1950s to its more widespread acceptance in the late 1960s may help us understand how a new technology makes its way into routine clinical practice.

Factors influencing HIV disclosure among people living with HIV/AIDS in Nigeria: a systematic review using narrative synthesis and meta-analysis.

OBJECTIVES: To critically review, appraise and evaluate quality of evidence on HIV disclosure among people living with HIV/AIDS (PLWHA) in Nigeria, and to identify a possible gap in knowledge on HIV/AIDS and disclosure. STUDY DESIGN: A systematic review using narrative synthesis and meta-analysis. METHODS: MedLine, PsycINFO, PubMed Central, Scopus and CINAHL were searched. Data were extracted with the use of spread sheet. An analysis of heterogeneity was performed for the disclosure rate and the presence of a supportive reaction from partners. A meta-analysis was performed for the disclosure rates to sexual partners, with data available for all ten studies. RESULTS: Ten studies met the inclusion criteria. The outcomes show that HIV disclosure of sero-positive status is most common between spouses or sexual partners than disclosure to relatives/family members, friends, pastor/Imam or work colleagues/employers. The participants in most of these studies are women, and amongst the most influential factors on disclosure are gender, anticipated outcome, marital status and knowledge of partners' status. Some studies reported non-disclosure as a way of limiting stigma. Almost all of the studies highlighted that there is fear of stigma and social exclusion associated with disclosure. CONCLUSION: This review discusses the overall experience of HIV disclosure on the management of the disease and barriers to disclosure. We found that PLWHA in Nigeria disclosed to at least one person within their social networks. Stigma is still a major consideration for PLWHA who experience a range of misconceptions around HIV transmission. The findings of this study may inform local policies and plans for improving the PLWHA quality of life. Targeted policies to increase disclosure of sero-positive status and reduce stigma may facilitate disease prevention. The methodological rigour of the included studies was appraised low.

ADAMTS-4 activity in synovial fluid as a biomarker of inflammation and effusion.

OBJECTIVE: To evaluate the potential of ADAMTS-4 (aggrecanase -1) activity in synovial fluid (SF) as a biomarker of knee injury and joint disease. DESIGN: We have measured ADAMTS-4 activity in the synovial fluid of 170 orthopaedic patients with different degrees of joint pathology, using a commercial ADAMTS-4 fluorescence resonance energy transfer (FRET) substrate assay. Patients were classified at arthroscopy as (i) macroscopically normal, (ii) with an injury of the meniscus, anterior cruciate ligament or chondral/osteochondral defects or (iii) with osteoarthritis, and the influence of independent factors (age, patient group, effusion and synovial inflammation) on ADAMTS-4 activity levels was assessed. RESULTS: In most patients (106/170) ADAMTS-4 activity was undetectable; ADAMTS-4 ranged from 0 to 2.8 ng/mL in synovial fluid from patients with an injury, 0-4.1 ng/mL in osteoarthritic patients and 4.0-12.3 ng/mL in patients with large effusions. Four independent variables each significantly influenced ADAMTS-4 activity in synovial fluid (all P < 0.001): age (concordance = 0.69), presence of osteoarthritis (OA) (concordance = 0.66), level of effusion (concordance = 0.78) and inflammation (concordance = 0.68). Not only did effusion influence the amount of ADAMTS-4 activity most strongly, but it also did this in an ordered manner (P < 0.001). CONCLUSIONS: The main finding of this study is that ADAMTS-4 levels in synovial fluid are most strongly correlated with inflammation and severity of effusion in the knee. Further study is required to determine if it could provide a useful tool to aid clinical diagnoses, indicate treatment, to monitor progression of joint degeneration or OA or alternatively the success of treatment.

Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?

OBJECTIVE: To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in England. POPULATION: All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

Long-term follow up of paediatric liver transplant recipients: outcomes following transfer to adult healthcare in New Zealand.

Poor outcomes are reported in young people with chronic health conditions. We performed a retrospective notes review of New Zealand paediatric liver transplant recipients transferred to adult services. Two patients were lost to follow up. Out of 20, 12 were non-adherent, and out of 12, 7 developed rejection. Other risk behaviours were common in the non-adherent group. We conclude that dedicated services for these young people may be needed to optimise outcomes.

Enhanced and persistent levels of interleukin (IL)-17⁺ CD4⁺ T cells and serum IL-17 in patients with early inflammatory arthritis.

Prognosis of patients with early inflammatory arthritis (EIA) is highly variable. The aim of this study was to compare, longitudinally and cross-sectionally, the levels of cytokine-expressing cells in peripheral blood (PB) from patients with EIA to those in established rheumatoid arthritis (RA) and healthy controls (HC). PB mononuclear cells from HC (n = 30), patients with EIA (n = 20) or RA (n = 38) were stimulated with phorbol myristate acetate (PMA)/ionomycin for 3 h, and stained for cell markers and cytokines. Serum cytokines and chemokines were measured by Luminex. Patients with EIA were reassessed at 6 and 12 months. The percentage of interleukin (IL)-17⁺ interferon (IFN)-γ⁻ CD4⁺ T cells [T helper type 17 (Th17)] was increased in RA and EIA versus HC. Serum IL-1ß, IL-2, IL-4 IL-17 and macrophage inflammatory protein (MIP)-1α were increased in RA and EIA versus HC. IL-1Ra, IL-15 and IFN-α were increased in EIA versus HC. IL-6 and tumour necrosis factor (TNF)-α was increased in RA but not EIA versus HC. Disease activity scores in EIA patients improved over 12 months' treatment. Th17 percentage at baseline was correlated with both rheumatoid factor (RF) titre and functional deficit at 12 months. Baseline levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-8 were correlated with Larsen score at 12 months. There were no significant changes in cytokine-expressing CD4⁺ T cells over time, although the percentage of IL-6⁺monocytes increased. IL-17⁺ CD4⁺ T cells and serum IL-17 levels are increased in EIA. IL-6-expressing monocytes increase during the first year of disease, irrespective of disease-modifying anti-rheumatic drug (DMARD) therapy. We observed incomplete clinical responses, suggesting EIA patients need more intensive early therapy.

Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight.

UNLABELLED: We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight. INTRODUCTION: This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. METHODS: We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. RESULTS: In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. CONCLUSIONS: The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.

BACKGROUND: During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. METHODS: A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. RESULTS: Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. CONCLUSION: e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.

Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure.

Lymphoma is a recognized cause of liver damage and in rare instances presents as ALF. In such cases, the underlying malignancy is often difficult to detect. Historically, the prognosis has been poor. Cure has occasionally been achieved with chemotherapy alone. LT in this setting is controversial, but has contributed to successful outcomes, as in the case of the five-yr-old girl reported here.

Medical management of severe obstructive sleep apnoea in two cases during the coronavirus disease 2019 pandemic.

OBJECTIVE: Severe paediatric obstructive sleep apnoea in typically developing children with adenotonsillar hypertrophy is primarily managed surgically. Non-emergency ENT surgery was paused early in the coronavirus disease 2019 pandemic and children were offered medical management for obstructive sleep apnoea. METHODS: A service evaluation was performed to assess the impact of continuous positive airway pressure alongside medical management for severe obstructive sleep apnoea. RESULTS: Over 5 months during 2020, in a tertiary care setting, two children (one boy and one girl), aged 2.7 years and 4.1 years, were offered continuous positive airway pressure and medical treatments for severe obstructive sleep apnoea whilst surgery was paused during the coronavirus disease 2019 pandemic. Both children failed to establish continuous positive airway pressure therapy because of ongoing disturbed sleep on ventilation, and they proceeded to adenotonsillectomy. Sleep-Related Breathing Disorder scale scores improved following surgical intervention. CONCLUSION: Continuous positive airway pressure therapy is poorly tolerated in children with severe obstructive sleep apnoea secondary to adenotonsillar hypertrophy. Surgery remains the most appropriate treatment.

An investigation to determine the normal 1st to 5th metatarsal peak pressure and PTI ratio of the forefoot.

BACKGROUND: The foot support has been described as that of a tripod. Biomechanical studies often report on peak pressures and pressure time integrals under specific areas of the foot. Reference needs to be made to the normal tripod distribution especially in the forefoot. In the forefoot the ratio between the 1st metatarsal and the 5th metatarsal on the medial and lateral columns of the foot respectively provide an excellent reference especially if the normal ratio is known. This study provides conclusive evidence of the 1st to 5th metatarsal ratio for peak pressures and pressure time integrals in the normal foot to be used as a reference. METHODS: A group of normal healthy volunteers (n = 12) and a group of patients with unilateral end stage hallux rigidus (n = 17) were recruited. Repeated measures of 1st and 5th metatarsal peak pressures and Pressure time integrals were measured to determine reliability of measurement and to provide a reference normal ratio. RESULTS: In the healthy volunteer group, the 1st/5th metatarsal ratio for PTI was very close to 1 while it was just over 1.5 for peak pressure. In patients with unilateral end stage hallux rigidus, in the normal foot the 1st/5th metatarsal ratio for PP and PTI was very close to 1. These ratios were reproduced in the operated foot following 1st MTPJ replacement. CONCLUSION: This study using normal healthy volunteers and patients undergoing 1st MTPJ replacement has demonstrated that the normal 1st/5th metatarsal peak pressure and pressure time integrals should be close to 1.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution.

OBJECTIVE: To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). DESIGN: Cohort study. SETTING: A large tertiary teaching hospital in London. POPULATION: Women who underwent repeat excisional treatment for treatment failure or persistent CIN. METHODS: Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. MAIN OUTCOME MEASURE: Differences in collagen expression were examined in the paired excisional treatment specimens. RESULTS: A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. CONCLUSION: There is no overall change in collagen distribution during regeneration following excisional treatment for CIN.