Diagnostic efficacy of chest CT imaging in diagnosis of COVID-19 cases based on duration of symptoms.

Background: Chest computed tomography (CT) imaging provides results more rapidly and with higher sensitivity than reverse transcription polymerase chain reaction in diagnosis of COVID-19. Aim: To evaluate diagnostic efficacy of chest CT imaging in diagnosis of COVID-19 cases based on age and duration of symptoms. Materials and Methods: A retrospective study conducted during December 2020 to June 2021 in a tertiary care hospital, India. Total 495 patients with typical clinical symptoms of COVID-19, reverse transcription polymerase chain reaction positive for COVID-19 and had undergone chest CT imaging were included. Descriptive statistical analysis was performed for all the variables. Receiver operating characteristic curve analysis was used to determine threshold value of chest CT severity score (CT_SS) based on duration of symptoms and age to diagnose COVID-19. Results: Mean age of patients was 61.86 ± 10.77 years and 367 (71.4%) patients were male. Ground glass opacities were observed in 456 (92.1%) patients and in 332 (67.1%) patients, multilobes were affected. Total CT_SS showed positive correlation with age (r = 0.257) and duration of symptoms (r = 0.625). Total CT_SS >6 after a duration of 2 days of symptoms identified COVID-19 cases with sensitivity 90.8% (95% confidence interval [CI]: 87.5%-93.5%) and specificity 84.6% (95% CI: 76.2%-90.9%). Total CT_SS >11 in patients aged more than 60 years identified COVID-19 cases with sensitivity 47.4% (95% CI: 41.2%-53.6%) and specificity 87.3% (95% CI: 82.3%-91.4%). Conclusion: Threshold value of CT_SS determined will help to expedite diagnosis of COVID-19 patients by the clinicians in an early stage especially in India and other developing countries which have a high patient volume and limited health resources.

Jewish cultural and religious factors and uptake of population-based BRCA testing across denominations: a cohort study.

OBJECTIVE: To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. DESIGN: Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). SETTING: London Ashkenazi-Jewish (AJ) population. POPULATION OR SAMPLE: AJ men and women, >18 years. METHODS: Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. MAIN OUTCOME MEASURES: Interest, intention, uptake of BRCA testing. RESULTS: In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. CONCLUSIONS: Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. TWEETABLE ABSTRACT: Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

Analysis of 55 cases of adenomatoid odontogenic tumor in an Indian population and review of literature.

BACKGROUND: This study reviews the demographic, clinical and radiographic features of adenomatoid odontogenic tumor(AOT) diagnosed in an Indian population over 50 years and also evaluate and compare follicular AOT(F-AOT) and extra-follicular AOT(EF-AOT). MATERIAL AND METHODS: 55 diagnosed cases of AOT from 1971-2020 were studied retrospectively. The data regarding the age, sex, location, variant of AOT, duration, clinical features, radiographic appearance, treatment and recurrence were collected and analysed. RESULTS: Of the 722 odontogenic tumors diagnosed, 7.6% were AOTs with higher prevalence of extra-follicular (67.3%) than follicular (32.7%) variant. All the tumors were intraosseous with a marked predilection for maxilla over mandible, ratio 2:1. The patients mean age was 19.8 years with slightly higher female predilection (male:female ratio - 1:1.5). The anterior region (76.4%) was more frequently affected and entire quadrant was involved in 21.8% cases. Clinically, asymptomatic, slow-growing swelling was seen in 81.8% cases with duration of 15 days to 10 years. Radiographically, AOT appeared as well-corticated radiolucent lesion. Canine was the most commonly impacted tooth. Recurrence was seen in 3 cases. CONCLUSIONS: Interestingly, in this series extra-follicular was twice more common than follicular AOT. Few cases involved the entire quadrant or crossed the midline of either jaws.

Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes.

OBJECTIVE: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. DESIGN: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. SETTING: North London Ashkenazi-Jewish (AJ) population. POPULATION/SAMPLE: AJ women/men. METHODS: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. INCLUSION CRITERIA: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. INTERVENTIONS: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. MAIN OUTCOME MEASURES: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. RESULTS: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97-4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89-2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74-2.26%). CONCLUSION: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. TWEETABLE ABSTRACT: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.

Prioritising health research in KwaZulu-Natal: has the research conducted met the research needs?

BACKGROUND: The KwaZulu-Natal (KZN) Health Act of 2009 mandates the Provincial Health Research and Ethics Committee to develop health research priorities for the province. During 2013, the KZN Department of Health embarked on a research prioritisation process for the province. Priority research questions were generated by an inclusive process, in which a variety of stakeholders in health research in the province were engaged. The aim of this study was to determine whether research conducted at public health facilities in KZN between 01 January 2014 and 31 March 2017 met the research priorities of the province developed through the provincial research prioritisation process of 2013. METHODS: This was a mixed methods study. Qualitative thematic analysis was used to categorise priority research questions generated in the priority-setting process and the titles of research projects conducted after that process into themes. Quantitative analysis was used to determine the correlation between themes of the priority questions, and those of the research projects conducted after the prioritisation exercise. Statistical Package for Social Science version 25 was used to analyse the data. RESULTS: In 72% of thematic areas, there were disproportionately more priority questions than there were research projects conducted. There is thus a large disjuncture between the priorities developed through the provincial research prioritisation process of 2013 and the research projects conducted after that process in terms of major research areas. CONCLUSIONS: Ensuring that research conducted responds to priority questions raised is important because it ensures that research responds to locally important issues and to the concerns of local actors. Local health managers, communities and researchers should work together to ensure that the research conducted in their areas respond to the research priorities of those areas. Health Research Committees and local ethics committees can play important roles in facilitating the responsiveness to research priorities.

Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study.

OBJECTIVE: To evaluate factors affecting unselected population-based BRCA testing in Ashkenazi Jews (AJ). DESIGN: Cohort-study set within recruitment to the GCaPPS trial (ISRCTN73338115). SETTING: North London AJ population. POPULATION OR SAMPLE: Ashkenazi Jews women/men >18 years, recruited through self-referral. METHODS: Ashkenazi Jews women/men underwent pre-test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio-demographic/family history/knowledge/psychological well-being along with benefits/risks/cultural influences (18-item questionnaire measuring 'attitude'). Four-item Likert-scales analysed initial 'interest' and 'intention-to-test' pre-counselling. Uni- and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item-Response Theory and graded-response models modelled responses to 18-item questionnaire. MAIN OUTCOME MEASURES: Interest, intention, uptake, attitude towards BRCA testing. RESULTS: A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre-test genetic-counselling. During the pre-counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA-related knowledge (P = 0.013) and degree-level education (P = 0.01) were positively and negatively (respectively) associated with intention-to-test. Being married/cohabiting had four-fold higher odds for BRCA testing uptake (P = 0.009). Perceived benefits were associated with higher pre-counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision-making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree-level education (P = 0.001) had weaker correlations, whereas having children showed stronger (P = 0.005) associations with attitudes towards BRCA testing. CONCLUSIONS: BRCA testing in the AJ population has high acceptability. Pre-test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost-benefit perception and decision-making on undergoing testing. TWEETABLE ABSTRACT: BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre-test counselling facilitates informed decision-making.

Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015.

BACKGROUND: Evidence suggests that continuing hydroxychloroquine (HCQ) during pregnancy in women with systemic lupus erythematosus (SLE) improves outcomes. We sought to describe time trends in the continuation, initiation, and duration of HCQ in a large population-based cohort of pregnant SLE women. METHODS: A cohort of pregnant women with SLE enrolled continuously in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2003-2015) health insurance between three months prior to conception and one month after delivery was identified. We assessed the proportion of women initiating or continuing HCQ and the duration of therapy during each calendar year in the study. RESULTS: A total of 5300 women with SLE were included. Of these, 852 (16.1%) were on HCQ treatment in the three-month period prior to their pregnancy. During pregnancy, the overall proportion of women with SLE taking HCQ increased from 12.4% in 2001 to 37.7% in 2015. Initiation of HCQ therapy during pregnancy increased from 2.7% in 2001 to 7.5% in 2010 ( p = 0.0002) (Medicaid) and from 4.9% in 2003 to 13.6% in 2015 ( p = 0.0001) (Clinformatics). Continuation of HCQ during pregnancy did not change significantly over time in either data set. The average cumulative day-supply of HCQ prescriptions during pregnancy increased from 37 days in 2001 to 77 days in 2010 ( p = 0.05) among HCQ initiators and from 79 days in 2001 to 125 days in 2010 ( p = 0.0009) among HCQ continuers in Medicaid. Among privately insured women, the average cumulative day-supply of HCQ prescriptions among HCQ continuers increased from 84 in 2004 to 163 in 2015 ( p = 0.0006) but did not change significantly among HCQ initiators. CONCLUSION: The proportion of women initiating HCQ during pregnancy and the average cumulative day-supply of HCQ increased from 2001 to 2015. While these findings are encouraging, overall HCQ use during pregnancy remains low.

Neonatal hyperlipidemia with pancreatitis: Novel gene mutation of lipoprotein lipase.

Lipoprotein lipase (LPL) deficiency is an autosomal recessive metabolic disorder with varying presentation in infancy and childhood, whereas clinical manifestations are rare in neonatal period. The estimated prevalence is one in a million births. A 23-day-old baby was admitted with complaints of fever, vomiting, and lethargy. Blood sample drawn appeared lipemic. Lipemia retinalis was noted on funduscopic examination. Biochemical analysis revealed abnormal lipid profile with severe hypertriglyceridemia (10,300 mg/dL) and elevated serum lipase level (517 IU/L) indicative of LPL deficiency with acute pancreatitis. LPL deficiency was suspected and was confirmed by molecular genetic testing, which revealed a novel mutation in LPL gene. Dietary management and gemfibrozil were started following which serum triglyceride level decreased and serum lipase level normalized. The patient is following up regularly for growth and development monitoring.

The association between biopsychosocial factors and disability in a national health survey in South Africa.

The association between psychosocial factors and disability is less clear. This study investigated the biological and psychosocial (employment and psychological distress) factors associated with level of disability in an adult sample in South Africa. Data were analysed from a cross-sectional survey among adults aged 18-64 (n = 4974). Multiple linear regression was used to investigate the associations of the selected variables with disability. The mean percentage score on the WHODAS scale of disability was 5.31% (95% CI: 4.74-5.88). Age (p < 0.001) and race (p = 0.0002) were significantly associated with disability, and history of stroke (ß = 7.19, 95% CI: 3.19-11.20) and heart-related conditions (ß = 2.08, 95% CI: [0.23-3.93) showed positive associations. Of the psychosocial variables, psychological distress (ß = 10.49 [8.63-12.35]) showed a strong positive association while employment (-1.62 [-2.36 to -0.88]) showed a negative association with disability. The association between demographic factors, medical conditions and increased disability confirms the findings in the literature. The finding that psychological distress is associated with increased disability has not been frequently reported. This study highlights specific psychosocial targets that may be usefully addressed by health policies and interventions in order to improve disability management.

Performance of mass spectrometry steroid profiling for diagnosis of polycystic ovary syndrome.

STUDY QUESTION: How well does multi-analyte steroid mass spectrometry (MS) profiling classify women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Our liquid chromatography MS (LC-MS) steroid profiling only minimally improves discrimination of women with and without PCOS compared with a direct testosterone immunoassay (T_IA) and the free androgen index (FAI). WHAT IS KNOWN ALREADY: Blood testosterone measured by direct (non-extraction) immunoassay overlaps between women with and without PCOS. Multi-analyte MS provides greater specificity and accuracy for steroid measurement so might improve the classification. STUDY DESIGN, SIZE, DURATION: An observational, cross-sectional study of women with PCOS (n = 152) defined by Rotterdam criteria and matched non-PCOS (n = 45) control women was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum steroid profiles of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione (A4), estradiol (E2), estrone (E1), 17 hydroxy progesterone (17OHP4), progesterone (P4) and cortisol were measured by LC-MS; T_IA and sex hormone binding globulin were measured by immunoassay; and FAI, calculated free testosterone (cFT) and total androgen index (TAI) were calculated. Classification was based on logistic regression with corresponding univariate and multivariate C-statistics. MAIN RESULTS AND THE ROLE OF CHANCE: Serum testosterone by immunoassay demonstrated levels more than 100% higher than that measured by LC-MS. Compared with the controls, women with PCOS had higher serum T, DHEA, A4, TAI, T_IA, cFT, FAI and E2 but not serum DHT, E1, P4, 17OHP4 or cortisol. Univariate C-statistics were highest for FAI (0.89) and T_IA (0.82) compared with other androgens (T [0.72], DHT [0.40]), pro-androgens (A4 [0.74], DHEA[0.71]) or derivatives (cFT [0.75], TAI [0.60]). For all multivariate models, the overall correct predictions (81-86%) featured high sensitivity (92-96%) but low specificity (28-43%). and substituting LC-MS steroid measurements for T_IA and FAI produced only minimal improvements in classification. LIMITATIONS REASONS FOR CAUTION: The study cohort is limited in size and only unconjugated steroids were measured. WIDER IMPLICATIONS OF THE FINDINGS: Multi-analyte steroid profiling of unconjugated circulating steroids provides only limited improvement on direct T_IA in classifying women with and without PCOS. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Biological and psychosocial risk factors for psychotic major depression.

AIMS: Few studies have investigated risk factors for psychotic major depression (PMD). We aimed to investigate the biological and psychosocial risk factors associated with PMD compared with other psychotic disorders. METHODS: Based on the aetiology and ethnicity in schizophrenia and other psychoses (ÆSOP) study, we used a case-control study to identify and recruit, at baseline and 10-year follow-up, all first episode cases of psychosis, presenting for the first time to specialist mental health services in defined catchment areas in the UK. Population-based controls were recruited from the same areas. Data were collected on: sociodemographics; social isolation; childhood adversity; life events; minor physical anomalies; and neurological soft signs. RESULTS: Living alone (aOR = 2.26, CI = 1.21-4.23), basic level qualification (aOR = 2.89, CI = 1.08-7.74), being unemployed (aOR = 2.12, CI = 1.13-3.96), having contact with friends less than monthly (aOR = 4.24, CI = 1.62-11.14), having no close confidants (aOR = 4.71, CI = 2.08-10.68), having experienced childhood adversity (aOR = 2.57, CI = 1.02-6.44), family history of mental illness (aOR = 10.68, CI = 5.06-22.52), family history of psychosis (aOR = 12.85, CI = 5.24-31.51), and having more neurological soft signs (aOR = 1.15, CI = 1.07-1.24) were all associated with a follow-up diagnosis of PMD and schizophrenia. Few variables associated with PMD were also associated with a diagnosis of bipolar disorder. Minor physical anomalies were associated with a follow-up diagnosis of schizophrenia and bipolar disorder, but not PMD. CONCLUSIONS: Risk factors associated with PMD appear to overlap with those for schizophrenia, but less so for bipolar disorder. Future work on the differential aetiology of PMD, from other psychoses is needed to find the 'specifier' between PMD and other psychoses. Future research on aetiology in PMD, and perhaps other psychoses, should account for diagnostic change.

Predictors of complications in gynaecological oncological surgery: a prospective multicentre study (UKGOSOC-UK gynaecological oncology surgical outcomes and complications).

BACKGROUND: There are limited data on surgical outcomes in gynaecological oncology. We report on predictors of complications in a multicentre prospective study. METHODS: Data on surgical procedures and resulting complications were contemporaneously recorded on consented patients in 10 participating UK gynaecological cancer centres. Patients were sent follow-up letters to capture any further complications. Post-operative (Post-op) complications were graded (I-V) in increasing severity using the Clavien-Dindo system. Grade I complications were excluded from the analysis. Univariable and multivariable regression was used to identify predictors of complications using all surgery for intra-operative (Intra-op) and only those with both hospital and patient-reported data for Post-op complications. RESULTS: Prospective data were available on 2948 major operations undertaken between April 2010 and February 2012. Median age was 62 years, with 35% obese and 20.4% ASA grade ⩾3. Consultant gynaecological oncologists performed 74.3% of operations. Intra-op complications were reported in 139 of 2948 and Grade II-V Post-op complications in 379 of 1462 surgeries. The predictors of risk were different for Intra-op and Post-op complications. For Intra-op complications, previous abdominal surgery, metabolic/endocrine disorders (excluding diabetes), surgical complexity and final diagnosis were significant in univariable and multivariable regression (P<0.05), with diabetes only in multivariable regression (P=0.006). For Post-op complications, age, comorbidity status, diabetes, surgical approach, duration of surgery, and final diagnosis were significant in both univariable and multivariable regression (P<0.05). CONCLUSIONS: This multicentre prospective audit benchmarks the considerable morbidity associated with gynaecological oncology surgery. There are significant patient and surgical factors that influence this risk.

Improved Standardization of the Bio-Rad Platelia Aspergillus Galactomannan Antigen Sandwich Enzyme Immunoassay Using the DS2 (Dynex) Enzyme-Linked Immunosorbent Assay (ELISA) Processing System.

The galactomannan enzyme immunoassay (GM-EIA) is widely utilized for the diagnosis of invasive aspergillosis (IA). There is inconsistent reproducibility of results between centers when the assay is processed manually. Automation of EIAs can reduce variation. This study investigated the semiautomation of the GM-EIA on the DS2 (Dynex) platform in the following three stages: (i) DS2 GM-EIA method validation with experimental samples, (ii) DS2 retesting of case-defined clinical samples, and (iii) a 12-month audit of DS2 GM-EIA performance. In stage i, Bland-Altman analysis demonstrated a reduced variance between optical density index (ODI) values for samples processed on two DS2 platforms (mean difference, -0.02; limits of agreement [LOA], -0.19 to 0.14) compared with the variance between samples processed manually and on a DS2 platform (mean difference, 0.02; LOA, -0.25 to 0.3). In stage ii, 100% (14/14 samples) qualitative agreement was observed for serum samples from patients with IA, with no significant change in the ODI values when samples were processed on the DS2 platform. A significant decrease in ODI values was observed for control serum samples on the DS2 platform (difference, 0.01; P = 0.042). In stage iii, a significant reduction in the frequency of equivocal results, from 5.56% (136/2,443 samples) to 1.56% (15/961 samples), was observed after DS2 automation (difference, 4.0%; 95% confidence interval [CI], 2.7 to 5.2%; P < 0.01), with an equivalent increase in negative results. This study demonstrates that GM-EIA automation may reduce intersite variability. Automation does not have an impact on the repeatability of truly positive results but contributes to a reduction in false-positive (equivocal) GM-EIA results, reducing the need to retest a significant proportion of samples.

Estimated risk of cancer transmission from organ donor to graft recipient in a national transplantation registry.

BACKGROUND: Transplanted organs carry the risk of inadvertent donor cancer transmission. Some cancers in organ donors have been classified as being associated with a high or unacceptable risk, but the evidence for such recommendations is scanty. METHODS: The risk of cancer transmission from donors characterized as high or unacceptable risk was studied by analysing transplant and cancer registry data. Donors and recipients from England (1990-2008) were identified from the UK Transplant Registry. Cancer details were obtained from cancer registries and classified using guidelines from the Council of Europe and Organ Procurement and Transplantation Network/United Network for Organ Sharing. RESULTS: Of 17,639 donors, 202 (1.1 per cent) had a history of cancer, including 61 donors with cancers classed as having an unacceptable/high risk of transmission. No cancer transmission was noted in 133 recipients of organs from these 61 donors. At 10 years after transplantation, the additional survival benefit gained by transplanting organs from donors with unacceptable/high-risk cancer was 944 (95 per cent confidence interval (c.i.) 851 to 1037) life-years, with a mean survival of 7.1 (95 per cent c.i. 6.4 to 7.8) years per recipient. CONCLUSION: Strict implementation of present guidelines is likely to result in overestimation of cancer transmission risk in some donors. Organs from some donors with cancers defined as unacceptable/high risk can be used safely.

Patient-reporting improves estimates of postoperative complication rates: a prospective cohort study in gynaecological oncology.

BACKGROUND: Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS: A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contemporaneously into an online database. Patients were sent follow-up letters to capture postoperative complications. Grade II-V (Clavien-Dindo classification) patient-reported postoperative complications were verified from hospital records. Postoperative complication rate was defined as the proportion of surgeries with a Grade II-V postoperative complication. RESULTS: Patient replies were received for 1462 (68%) of 2152 surgeries undertaken between April 2010 and February 2012. Overall, 452 Grade II-V (402 II, 50 III-V) complications were reported in 379 of the 1462 surgeries. This included 172 surgeries with 200 hospital-reported complications and 231 with 280 patient-reported complications. All (100% concordance) 36 Grade III-V and 158 of 280 (56.4% concordance) Grade II patient-reported complications were verified on hospital case-note review. The PCR using hospital-reported data was 11.8% (172 out of 1462; 95% CI 11-14), patient-reported was 15.8% (231 out of 1462; 95% CI 14-17.8), hospital and verified patient-reported was 19.4% (283 out of 1462; 95% CI 17.4-21.4) and all data were 25.9% (379 out of 1462; 95% CI 24-28). After excluding Grade II complications, the hospital and patient verified Grade III-V PCR was 3.3% (48 out of 1462; 95% CI 2.5-4.3). CONCLUSION: This is the first prospective study of postoperative complications we are aware of in gynaecological oncology to include the patient-reported data. Patient-reporting is invaluable for obtaining complete information on postoperative complications. Primary care case-note review is likely to improve verification rates of patient-reported Grade II complications.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer.

BACKGROUND: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. METHODS: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case-control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. RESULTS: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. CONCLUSION: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection.

How much does a minimum weight at discharge delay discharge from the neonatal intensive care unit?

BACKGROUND: Current American Academy of Pediatrics guidelines recommend discharge at physiologic maturity regardless of weight; however, our institution's neonatal ICU policy requires a minimum weight of 1800 g for discharge even when infant is physiologically mature. So, we wanted to determine if discharge at physiologic maturity (PM), based on national guidelines, would decrease hospital days (HD). METHODS: We reviewed 129 infants with birthweight 1300g- 1800 g. Data were analyzed by paired t-test/ Wilcoxon-rank-sum test. RESULTS: Age at discharge vs. age at PM was 0.55d per infant higher (P-value 0.033) resulting in 71 total HD. For SGA babies, this difference was 1.47d vs 0.19d in non-SGA babies (P- value 0.0243) and this difference was an average of 2.63d (P-value < 0.001) for those who reached PM < 1800 g, contributing to 50 of 71 HD potentially saved. CONCLUSION: There was a 0.55-2.6-day difference between age at discharge and age at PM, greater in SGA infants and infants who reached PM prior to 1800 g. There might be an opportunity to send infants home earlier to their families if there is no minimum weight required.

Status of Vitamin B12, Zinc, Copper, Selenium, Manganese, Molybdenum and Cobalt in Severe Acute Malnutrition.

OBJECTIVES: To define the vitamin B12 levels and other micronutrients status in severe acute malnutrition (SAM) children. METHODS: This was a prospective hospital based cross-sectional study. INCLUSION CRITERIA: Children with severe acute malnutrition as per WHO criteria. EXCLUSION CRITERIA: (i) Pernicious anemia (ii) Autoimmune gastritis (iii) SAM children on exclusive vitamin B12 supplementation. All enrolled children underwent a detailed clinical history, general physical examination with more emphasis on clinical features of vitamin B12 and other micronutrients deficiencies. Three ml of venous blood was collected to estimate vitamin B12 and other micronutrients. Primary outcome was percentage of deficiency of serum vitamin B12, zinc, copper, selenium, manganese, molybdenum and cobalt in SAM children. RESULTS: Fifty children were included in the study. The mean age of children was 15.60±12.90 mo with male to female ratio 0.85:1. The common clinical presentation in order of frequency were upper respiratory infection (URI) symptoms 35 (70%), hepatomegaly 24 (48%), Hyperpigmentation 17 (34%), angular cheilitis 14 (28%), tremors 11 (22%), edema 07 (14%), and hypotonia 05 (10%). Anemia was found in 44 (88%) children. Prevalence of vitamin B12 deficiency was 34%. Other micronutrient deficiencies observed were cobalt 24 (100%), copper 05 (12%), zinc 04 (9.5%), and molybdenum 03 (12.5%). No statistical significance was found between clinical symptoms and levels of vitamin B12 with different age and sex. CONCLUSIONS: Prevalence of low vitamin B12 and cobalt were more common than other micronutrients.

NLX-112, a highly selective 5-HT1A receptor biased agonist, does not exhibit misuse potential in male rats or macaques.

NLX-112 (a.k.a. F13640 or befiradol) exhibits nanomolar affinity, exceptional selectivity and biased agonism at serotonin 5-HT1A receptors. NLX-112 displays robust analgesic activity in a number of rodent models of pain, and is currently developed as a treatment for l-DOPA-induced dyskinesia (LID) in Parkinson's disease (PD) patients. Noteworthy, PD patients can suffer from comorbid chronic pain, thus necessitating the use of analgesic drugs, such as opioids, which have potential for misuse. Additionally, dopamine agonists used to treat PD can produce cocaine-like effects in preclinical assays of misuse potential. The present study investigated whether NLX-112 possesses misuse potential of its own using two behavioural assays routinely used for this purpose: intracranial self-stimulation (ICSS) in rats, and cocaine discrimination in macaque monkeys. In rats, low doses of NLX-112 (0.03 and 0.1 mg/kg p.o.) did not alter ICSS frequency-rate curves, while higher doses (0.3 and 1.0 mg/kg) shifted the curve to the right and flattened it, i.e., reduced ICSS. As expected, cocaine (10 mg/kg i.p.) shifted the curve to the left, i.e., facilitated ICSS, but NLX-112 (0.03 and 0.1 mg/kg p.o.) did not further enhance cocaine-induced facilitation of ICSS. In monkeys trained to discriminate cocaine (0.4 mg/kg i.m.) from saline, NLX-112 (0.01-0.1 mg/kg p.o.) did not substitute for cocaine. Taken together, these results suggest that NLX-112, at doses displaying anti-dyskinetic activity in rat, marmoset and macaque models of LID, is free from misuse potential. From a translational perspective, this is a desirable property for a compound destined to be used in PD patients, who can suffer from comorbid chronic pain necessitating the use of potentially misused analgesic drugs.