Open abdominal wall defects and open spina bifida at a regional hospital in northern KwaZulu-Natal - bellwether conditions for neonatal surgery capacity.

BACKGROUND: Abdominal wall defects (AWDs), such as gastroschisis and omphalocele, and neural tube defects (NTDs) such as open spina bifida (SB) are common congenital anomalies. These anomalies are considered a leading cause of neonatal mortality and have been advocated as bellwether conditions to measure access to surgical care. METHODS: Newborns with open SB or AWD presenting to the nursery at Queen Nandi Regional Hospital over four years (2018-2021) were retrospectively identified. Clinical and electronic database records were reviewed to determine if transfers to definitive tertiary care occurred timeously. Reasons for delays and associated morbidity and/or mortality were investigated. RESULTS: Sixty-five patients were identified and two were excluded due to unavailable or incomplete records. It took a median of 8 days (IQR 2-18 days) to reach tertiary care, with SB cases waiting significantly longer (median 16 days,IQR 8-25 days) (p = 0.000). Lack of tertiary service capacity was the main reason for delays. The COVID-19 pandemic did not affect time intervals (p = 0.676). Complications were common and overall mortality at our facility was high (n = 11/63, 17.46%). CONCLUSION: Newborns with open SB or AWDs experience marked delays in reaching definitive care. This is more pronounced for cases of SB and was not influenced by the pandemic. Lack of tertiary service capacity (including bed availability, limited staff, and theatre time) is the most important limiting factor.

Association of hysterectomy and invasive epithelial ovarian and tubal cancer: a cohort study within UKCTOCS.

OBJECTIVE: To investigate the association between hysterectomy with conservation of one or both adnexa and ovarian and tubal cancer. DESIGN: Prospective cohort study. SETTING: Thirteen NHS Trusts in England, Wales and Northern Ireland. POPULATION: A total of 202 506 postmenopausal women recruited between 2001 and 2005 to the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and followed up until 31 December 2014. METHODS: Multiple sources (questionnaires, hospital notes, Hospital Episodes Statistics, national cancer/death registries, ultrasound reports) were used to obtain accurate data on hysterectomy (with conservation of one or both adnexa) and outcomes censored at bilateral oophorectomy, death, ovarian/tubal cancer diagnosis, loss to follow up or 31 December 2014. Cox proportional hazards regression models were used to assess the association. MAIN OUTCOME MEASURES: Invasive epithelial ovarian and tubal cancer (WHO 2014) on independent outcome review. RESULTS: Hysterectomy with conservation of one or both adnexa was reported in 41 912 (20.7%; 41 912/202 506) women. Median follow up was 11.1 years (interquartile range 9.96-12.04), totalling >2.17 million woman-years. Among women who had undergone hysterectomy, 0.55% (231/41 912) were diagnosed with ovarian/tubal cancer, compared with 0.59% (945/160 594) of those with intact uterus. Multivariable analysis showed no evidence of an association between hysterectomy and invasive epithelial ovarian/tubal cancer (hazard ratio 0.98, 95% CI 0.85-1.13, P = 0.765). CONCLUSIONS: This large cohort study provides further independent validation that hysterectomy is not associated with alteration of invasive epithelial ovarian and tubal cancer risk. These data are important both for clinical counselling and for refining risk prediction models. TWEETABLE ABSTRACT: Hysterectomy does not alter risk of invasive epithelial ovarian and tubal cancer.

Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction.

Deficiency in Sphingosine-1-phosphate lyase (S1P lyase) is associated with a multi-systemic disorder incorporating primary adrenal insufficiency (PAI), steroid resistant nephrotic syndrome and neurological dysfunction. Accumulation of sphingolipid intermediates, as seen with loss of function mutations in SGPL1, has been implicated in mitochondrial dysregulation, including alterations in mitochondrial membrane potentials and initiation of mitochondrial apoptosis. For the first time, we investigate the impact of S1P lyase deficiency on mitochondrial morphology and function using patient-derived human dermal fibroblasts and CRISPR engineered SGPL1-knockout HeLa cells. Reduced cortisol output in response to progesterone stimulation was observed in two patient dermal fibroblast cell lines. Mass spectrometric analysis of patient dermal fibroblasts revealed significantly elevated levels of sphingosine-1-phosphate, sphingosine, ceramide species and sphingomyelin when compared to control. Total mitochondrial volume was reduced in both S1P lyase deficient patient and HeLa cell lines. Mitochondrial dynamics and parameters of oxidative phosphorylation were altered when compared to matched controls, though differentially across the cell lines. Mitochondrial dysfunction may represent a major event in the pathogenesis of this disease, associated with severity of phenotype.

Current and future approaches to screening for endometrial cancer.

Due largely to the rise in obesity and prolonged life expectancy, endometrial cancer (EC) rates have increased by 56% since the early 90s. Women at high risk (Lynch Syndrome) have a 12-47% lifetime risk of developing EC and professional societies recommend annual surveillance using transvaginal ultrasound (TVS) and endometrial biopsy (outpatients hysteroscopy) from the age of 30-35 years with hysterectomy from the age of 40 years. In women at low risk, screening is not currently advocated. The emerging data from Genome Wide Association studies (GWAS) in combination with epidemiological data may refine risk stratification in the future. In addition to screening, preventative approaches such as intrauterine progesterone may help reduce disease burden in those identified at 'higher risk'.

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings.

BACKGROUND: Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) last published their respective recommendations for the management of PsA in 2015. However, these guidelines are primarily based on studies conducted in resource replete countries and may not be applicable in countries in the Americas (except Canada and USA) and Africa. We sought to adapt the existing recommendations for these regions under the auspices of the International League of Associations for Rheumatology (ILAR). PROCESS: The ADAPTE Collaboration (2009) process for guideline adaptation was followed to adapt the EULAR and GRAPPA PsA treatment recommendations for the Americas and Africa. The process was conducted in three recommended phases: set-up phase; adaptation phase (defining health questions, assessing source recommendations, drafting report), and finalization phase (external review, aftercare planning, and final production). RESULT: ILAR recommendations have been derived principally by adapting the GRAPPA recommendations, additionally, EULAR recommendations where appropriate and supplemented by expert opinion and literature from these regions. A paucity of data relevant to resource-poor settings was found in PsA management literature. CONCLUSION: The ILAR Treatment Recommendations for PsA intends to serve as reference for the management of PsA in the Americas and Africa. This paper illustrates the experience of an international working group in adapting existing recommendations to a resource-poor setting. It highlights the need to conduct research on the management of PsA in these regions as data are currently lacking.Key Points• The paper presents adapted recommendations for the management of psoriatic arthritis in resource-poor settings.• The ADAPTE process was used to adapt existing GRAPPA and EULAR recommendations by collaboration with practicing clinicians from the Americas and Africa.• The evidence from resource-poor settings to answer clinically relevant questions was scant or non-existent; hence, a research agenda is proposed.

Serial endometrial thickness and risk of non-endometrial hormone-dependent cancers in postmenopausal women in UK Collaborative Trial of Ovarian Cancer Screening.

OBJECTIVE: Estrogen is a well-established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non-endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non-endometrial hormone-sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. METHODS: This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50-74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen-dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time-to-event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non-Hodgkin's lymphoma (NHL). All models were adjusted for current hormone-replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. RESULTS: The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5-9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow-up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09-1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06-1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02-1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. CONCLUSION: Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

People living with HIV and COVID-19: A report on 2 clinical cases from South Africa.

The impact of HIV in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been well established. It is uncertain if outcomes are better or worse in these patients compared with COVID-19 patients with diabetes mellitus, hypertension and other chronic diseases. The course and outcome is also unknown in HIV-positive patients who are virally suppressed on antiretroviral treatment (ART) compared with those who are treatment-naive. We present two HIV-positive cases with COVID-19 pneumonia - one virally suppressed and the other newly diagnosed. Both patients had favourable outcomes.

The role of transvaginal ultrasound in screening for ovarian cancer.

Ovarian cancer is a low-prevalence postmenopausal cancer with a high mortality rate and is the fifth most lethal cancer in women. The most common serous subtype with TP53 mutations spreads rapidly throughout the peritoneal cavity (stage III/IV) when 5-year survival is 10%. If diagnosed while confined to the ovary (stage I), the survival rate exceeds 90%. This is the rationale for screening. Annual transvaginal ultrasound (TVU) scans used as a primary screening modality or as a second-line test following primary screening with serum CA125 (multimodal) have been investigated in several trials. Only two large randomized controlled trials have provided mortality data. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial studied over 78 000 women (randomized to screening with either TVU or CA125, or control) over 6 years with 14 years follow-up and found no mortality benefit from screening and increased morbidity in the screened arm. The UK Collaborative Trial of Ovarian Cancer Screening studied over 202 000 women randomized to TVU, multimodal or control in a 1 : 1 : 2 ratio over 7-11 years with 11 years follow-up. CA125 was interpreted by the Risk of Ovarian Cancer algorithm which identifies a rise in the level rather than a fixed cut-off. There was a late reduction in mortality after 7 years in the screened arm (23% in the multimodal arm and 21% in the TVU arm), but the overall reduction was not significant. Further follow-up may reveal whether TVU has a primary or secondary role in ovarian cancer screening.

Association between skirt size and chronic liver disease in post-menopausal women: a prospective cohort study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: We investigated the association between self-reported skirt size (SS) and change in SS, and incidence of chronic liver disease (CLD) in a prospective cohort study of women recruited to the UKCTOCS trial. METHODS: Women recruited to UKCTOCS in England without documented CLD self-reported their current UK SS during trial participation and were asked to recall their SS when aged in 20s (via completion of a questionnaire 3-5 years after recruitment). Participants were followed up via electronic health record linkage and hazard ratios (HR) calculated for incident liver-related events (LRE). RESULTS: Three hundred twenty-two (0.3%) of 94,124 women experienced a first LRE. Compared to SS ≤ 16, rates of LRE were higher in the SS ≥ 18 groups (both when aged in 20s and at questionnaire completion). Event rates were higher if there was no change in SS or an increase in SS, compared to a decrease in SS. In the models adjusted for potential confounders, HRs for LRE were higher in the groups of women reporting SS ≥ 18 both when aged in 20s (HR = 1.39 (95% CI; 0.87-2.23)) and at questionnaire completion (HR = 1.37 (95% CI; 1.07-1.75)). Compared to a decrease in SS, HRs were higher in the no change (HR = 1.78 (95% CI; 0.95-3.34)) and increase (HR = 1.80 (95% CI; 1.01-3.21)) groups. CONCLUSION: CLD is associated with high SS and an increase in SS over time. These data suggest SS can be used in simple public health messages about communicating the risk of liver disease. TRIAL REGISTRATION: UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978 . Registered 06/04/2000.

Sonographers' self-reported visualization of normal postmenopausal ovaries on transvaginal ultrasound is not reliable: results of expert review of archived images from UKCTOCS.

OBJECTIVE: In the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), self-reported visualization rate (VR) of the ovaries by the sonographer on annual transvaginal sonographic (TVS) examinations was a key quality control (QC) metric. The objective of this study was to assess self-reported VR using expert review of a random sample of archived images of TVS examinations from UKCTOCS, and then to develop software for measuring VR automatically. METHODS: A single expert reviewed images archived from 1000 TVS examinations selected randomly from 68 931 TVS scans performed in UKCTOCS between 2008 and 2011 with ovaries reported as 'seen and normal'. Software was developed to identify the exact images used by the sonographer to measure the ovaries. This was achieved by measuring caliper dimensions in the image and matching them to those recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimensions and visualization data reported by the expert. RESULTS: The expert reviewer confirmed visualization of both ovaries (VR-Both) in 50.2% (502/1000) of the examinations. The software identified the measurement image in 534 exams, which were split 2:1:1 providing training, validation and test data. Classifier mean accuracy on validation data was 70.9% (95% CI, 70.0-71.8%). Analysis of test data (133 exams) provided a sensitivity of 90.5% (95% CI, 80.9-95.8%) and specificity of 47.5% (95% CI, 34.5-60.8%) in detecting expert confirmed visualization of both ovaries. CONCLUSIONS: Our results suggest that, in a significant proportion of TVS annual screens, the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude that QC metrics based on self-reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

An Exploratory Analysis of Referrals to a major Emergency Department in a developing country

Background: Hospital crowding, ED waiting times and high demand for unscheduled care all place significant burdens on secondary care services. This impacts on patient care, staff morale and overall functioning of the whole healthcare system. Patient referrals from other healthcare providers often is a result of limited access to resources, specialists or because of acuity. However, some referrals may be more suitable for lower acuity settings, with the benefit of better overall patient experience. In addition, duplication of contacts with a healthcare professional may not result in additional benefit to patients, but may necessarily add to the patient journey and contribute to crowding. Objectives: We aimed to determine the originator of referrals to the ED. We also aimed to determine the proportion of referred patients who received any meaningful intervention at the ED. Finally, we aimed to estimate the proportion of patients referred who may have been suitable for direct inpatient referral or management in a lower acuity setting. Methods: We conducted a prospective evaluation of all referrals to the ED of a large urban hospital over 7 days. Routine anonymised demographic, diagnosis and intervention data were collected and simple descriptive analysis was undertaken using Microsoft Excel®. A validated algorithm was applied to determine suitability for lower acuity settings, and contextual secondary analysis was applied to determine choice of altResults: There were 168 formal referrals during the period evaluated (mean 24/day), of which data was available for 151. Most referrals were on Monday and Thursday. 39.7% were referred from the four regional District Health Facilities (DHF). 12 % were referred by specialists. There were significantly higher referrals from Local Health Centres located more than 5km of the hospital compared with those closer, although this could have been due to greater numbers outside the 5 km radius. 5.5% were thought suitable for primary care management and 31% could have been referred directly to an inpatient team if this were available. The majority (51.3%) of referred patients received no significant intervention in the ED, with almost 1 in 7 suitable for outpatient management. Conclusions: A significant number of patients referred to the ED may have been more appropriately directed. Direct special admission, access to outpatient referral slots or telephone advice from senior ED or specialty clinicians may prevent up to a half of referrals being seen by an ED clinician. This may reduce unnecessary transport, improve time and resource utilization and decongest the ED and hospital. Further large scale evaluation is warranted to investigate the predictors of referral, control for seniority, and make more robust recommendations for improving the patient journey ernate pathways.

Prevalence and predictors of complementary and alternative medicine/non-pharmacological interventions use for menopausal symptoms within the UK Collaborative Trial of Ovarian Cancer Screening.

OBJECTIVES: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) and non-pharmacological interventions (NPI) for menopausal symptom relief. We report on the prevalence and predictors of CAM/NPI among UK postmenopausal women. METHOD: Postmenopausal women aged 50-74 years were invited to participate in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). A total of 202 638 women were recruited and completed a baseline questionnaire. Of these, 136 020 were sent a postal follow-up-questionnaire between September 2006 and May 2009 which included ever-use of CAM/NPI for menopausal symptom relief. Both questionnaires included MHT use. RESULTS: A total of 88 430 (65.0%) women returned a completed follow-up-questionnaire; 22 206 (25.1%) reported ever-use of one or more CAM/NPI. Highest use was reported for herbal therapies (43.8%; 9725/22 206), vitamins (42.6%; 9458/22 206), lifestyle approaches (32.1%; 7137/22 206) and phytoestrogens (21.6%; 4802/22 206). Older women reported less ever-use of herbal therapies, vitamins and phytoestrogens. Lifestyle approaches, aromatherapy/reflexology/acupuncture and homeopathy were similar across age groups. Higher education, Black ethnicity, MHT or previous oral contraceptive pill use were associated with higher CAM/NPI use. Women assessed as being less hopeful about their future were less likely to use CAM/NPI. CONCLUSION: One in four postmenopausal women reported ever-use of CAM therapies/NPI for menopausal symptom relief, with lower use reported by older women. Higher levels of education and previous MHT use were positive predictors of CAM/NPI use. UKCTOCS Trial registration: ISRCTN22488978.

Ideal charge-density-wave order in the high-field state of superconducting YBCO.

The existence of charge-density-wave (CDW) correlations in cuprate superconductors has now been established. However, the nature of the CDW ground state has remained uncertain because disorder and the presence of superconductivity typically limit the CDW correlation lengths to only a dozen unit cells or less. Here we explore the field-induced 3D CDW correlations in extremely pure detwinned crystals of YBa2Cu3O2 (YBCO) ortho-II and ortho-VIII at magnetic fields in excess of the resistive upper critical field ([Formula: see text]) where superconductivity is heavily suppressed. We observe that the 3D CDW is unidirectional and possesses a long in-plane correlation length as well as significant correlations between neighboring CuO2 planes. It is significant that we observe only a single sharply defined transition at a critical field proportional to [Formula: see text], given that the field range used in this investigation overlaps with other high-field experiments including quantum oscillation measurements. The correlation volume is at least two to three orders of magnitude larger than that of the zero-field CDW. This is by far the largest CDW correlation volume observed in any cuprate crystal and so is presumably representative of the high-field ground state of an "ideal" disorder-free cuprate.

Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study.

OBJECTIVE: To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres. DESIGN: Prospective cohort study. SETTING: Ten UK accredited gynaecological oncology centres. POPULATION: Women undergoing major surgery on a gynaecological oncology operating list. METHODS: Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors. MAIN OUTCOME MEASURES: Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken. RESULTS: Overall, IntraOp CR was 4.7% (95% CI 4.0-5.6) and PostOp CR was 25.7% (95% CI 23.7-28.2). The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95-98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs. CONCLUSION: The funnel plots and overall IntraOp (≈5%) and PostOp (≈26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk-adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important. TWEETABLE ABSTRACT: Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison.

Quality assurance and its impact on ovarian visualization rates in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualization of postmenopausal ovaries in the ultrasound arm of a multicenter screening trial for ovarian cancer. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 50 639 women aged 50-74 years were randomized to the ultrasound arm and underwent annual transvaginal ultrasound (TVS) examinations. QA processes were developed during the course of the trial and included regular monitoring of the visualization rate (VR) of the right ovary. Non-subjective factors identified previously as impacting on VR of the right ovary were included in a generalized estimating equation model for binary outcomes to enable comparison of observed vs adjusted VR between individual sonographers who had undertaken > 1000 scans during the trial and comparison between centers. Observed and adjusted VRs of sonographers and centers were ranked according to the highest VR. Analysis of annual VRs of sonographers and those of the included centers was undertaken. RESULTS: Between June 2001 and December 2010, 48 230 of 50 639 women attended one of 13 centers for a total of 270 035 annual TVS scans. One or both ovaries were seen in 228 145 (84.5%) TVS scans. The right ovary was seen on 196 426 (72.7%) of the scans. For the 78 sonographers included in the model, the median difference between observed and adjusted VR was -0.7% (range, -7.9 to 5.9%) and the median change in VR rank after adjustment was 3 (range, 0-18). For the 13 centers, the median difference between observed and adjusted VR was -0.5% (range, -2.2 to 1%), with no change in ranking after adjustment. The median adjusted VR was 73% (interquartile range (IQR), 65-82%) for sonographers and 74.7% (IQR, 67.1-79.0%) for centers. Despite the increasing age of the women being scanned, there was a steady decrease in the number of sonographers with VR < 60% (21.4% in 2002 vs 2.0% in 2010) and an increase in sonographers with VR > 80% (14.3% in 2002 vs 40.8% in 2010). The median VR of the centers increased from 65.5% (range, 55.7-81.0%) in 2001 to 80.3% (range, 74.5-90.9%) in 2010. CONCLUSIONS: A robust QA program can improve visualization of postmenopausal ovaries and is an essential component of ultrasound-based ovarian cancer screening trials. While VR should be adjusted for non-subjective factors that impact on ovarian visualization, subjective factors are likely to be the largest contributors to differences in VR.

Time to diagnosis of Type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records.

OBJECTIVE: To compare time to diagnosis of the typically slow-growing Type I (low-grade serous, low-grade endometrioid, mucinous, clear cell) and the more aggressive Type II (high-grade serous, high-grade endometrioid, undifferentiated, carcinosarcoma) invasive epithelial ovarian cancer (iEOC). DESIGN: Multicentre observational study. SETTING: Ten UK gynaecological oncology centres. POPULATION: Women diagnosed with primary EOC between 2006 and 2008. METHODS: Symptom data were collected before diagnosis using patient questionnaire and primary-care records. We estimated patient interval (first symptom to presentation) using questionnaire data and diagnostic interval (presentation to diagnosis) using primary-care records. We considered the impact of first symptom, referral and stage on intervals for Type I and Type II iEOC. MAIN OUTCOME MEASURES: Patient and diagnostic intervals. RESULTS: In all, 78% of 60 Type I and 21% of 134 Type II iEOC were early-stage. Intervals were comparable and independent of stage [e.g. median patient interval for Type I: early-stage 0.3 months (interquartile range 0.3-3.0) versus late-stage 0.3 months (interquartile range 0.3-4.5), P = 0.8]. Twenty-seven percent of women with Type I and Type II had diagnostic intervals of at least 9 months. First symptom (questionnaire) was also similar, except for the infrequent abnormal bleeding (Type I 15% versus Type II 4%, P = 0.01). More women with Type I disease (57% versus 41%, P = 0.04) had been referred for suspected gynaecological cancer. Median time from referral to diagnosis was 1.4 months for women with iEOC referred via a 2-week cancer referral to any specialty compared with 2.6 months (interquartile range 2.0-3.7) for women who were referred routinely to gynaecology. CONCLUSION: Overall, shorter diagnostic delays were seen when a cancer was suspected, even if the primary tumour site was not recognised to be ovarian. Despite differences in carcinogenesis and stage for Type I and Type II iEOC, time to diagnosis and symptoms were similar. Referral patterns were different, implying subtle symptom differences. If symptom-based interventions are to impact on ovarian cancer survival, it is likely to be through reduced volume rather than stage-shift. Further research on histological subtypes is needed. TWEETABLE ABSTRACT: No difference in time to diagnosis for Type I versus Type II invasive epithelial ovarian cancers.

Multilocus DNA sequencing of the whiskey fungus reveals a continental-scale speciation pattern.

Baudoinia was described to accommodate a single species, B. compniacensis. Known as the 'whiskey fungus', this species is the predominant member of a ubiquitous microbial community known colloquially as 'warehouse staining' that develops on outdoor surfaces subject to periodic exposure to ethanolic vapours near distilleries and bakeries. Here we examine 19 strains recovered from environmental samples near industrial settings in North America, South America, the Caribbean, Europe and the Far East. Molecular phylogenetic analysis of a portion of the nucLSU rRNA gene confirms that Baudoinia is a monophyletic lineage within the Teratosphaeriaceae (Capnodiales). Multilocus phylogenetic analysis of nucITS rRNA (ITS1-5.8S-ITS2) and partial nucLSU rRNA, beta-tubulin (TUB) and elongation factor 1-alpha (TEF1) gene sequences further indicates that Baudoinia consists of five strongly supported, geographically patterned lineages representing four new species (viz. Baudoinia antilliensis, B. caledoniensis, B. orientalis and B. panamericana).

Psoriatic Arthritis: An Assessment of Clinical; Biochemical and Radiological Features in a Single-Centre South African Cohort

BACKGROUND:Although psoriatic arthritis (PsA) is a well-documented clinical entity; epidemiological; clinical and radiological studies of South African (SA) patients are scarce.OBJECTIVES:To assess clinical; biochemical and radiological features in a single-centre SA cohort.METHODS: We conducted a prospective assessment of the clinical; biochemical and radiological features of 384 consecutive patients with PsA seen at the rheumatology clinic at Prince Mshiyeni Memorial Hospital; Durban; SA; between January 2007 and December 2013. Patients were assessed at enrolment and 6 months after enrolment. They were classified into five groups as described by Moll and Wright; being entered into the group that best described the clinical manifestations. Clinicopathological characteristics recorded at enrolment were age at the time of examination; racial background; personal and family medical history; age and symptoms at the onset of PsA; pattern of joint involvement; joint pain; and the relationship between joint pain and the onset of PsA.RESULTS:Of the patients; 59.1% had a polyarticular presentation indistinguishable from rheumatoid arthritis; 19.0% had distal interphalangeal involvement; 9.1% had spondyloarthropathy; 11.9% had oligoarthritis and 0.9% had arthritis mutilans. The epidemiological trends (male/female ratio 1.45:1; mean age at onset of arthritis 50.2 (standard deviation 11.8) years; female preponderance in the polyarticular group and male preponderance in the spondyloarthropathy and oligoarticular groups) were similar to trends published elsewhere. A notable characteristic of our cohort was the complete absence of black South Africans with PsA.CONCLUSIONS:The complete absence of black South Africans with PsA is interesting. We anticipate that our findings will prompt genetic studies to isolate both protective and susceptibility genes for further elucidating PsA

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.(AU)

Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples.

BACKGROUND: Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort. METHODS: This nested case-control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups. RESULTS: CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml(-1) the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml(-1), sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17-24 months for test-positive cases. CONCLUSIONS: CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.