Identification of metastatic papillary thyroid carcinoma in FNA specimens using thyroid peroxidase immunohistochemistry.

INTRODUCTION: We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. METHODS: Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma). Thyroid tumours were stained with TTF1 and Tg in addition to TPO. All cases of metastatic lung carcinoma also had TTF-1 staining results. RESULTS: TPO staining was negative in all non-thyroid malignancies. Ninety percent (26/29) of PTC were positive. All positive cases showed strong cytoplasmic staining, although 54% (14/26) showed positivity in less than half of the cells. By comparison, Tg staining of TPC cases was present in 62% and TTF-1 in 100%. In addition to showing higher sensitivity, interpretation of staining results with TPO was generally easier with than Tg. All metastatic lung adenocarcinomas were positive for TTF-1 and TPO negative. The six medullary cancers showed positivity in 17%, 0% and 83% with TPO, Tg and TTF-1, respectively. CONCLUSIONS: TPO (mAb EP159) may be a useful addition to immunohistochemical panels for FNA specimens where metastatic PTC is a consideration, particularly in cases where metastatic lung carcinoma features in the differential diagnosis.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the UK's Haematological Malignancy Research Network.

BACKGROUND: Population-based information about cancer occurrence and survival are required to inform clinical practice and research; but for most lymphomas data are lacking. METHODS: Set within a socio-demographically representative UK population of nearly 4 million, lymphoma data (N=5796) are from an established patient cohort. RESULTS: Incidence, survival (overall and relative) and prevalence estimates for >20 subtypes are presented. With few exceptions, males tended to be diagnosed at younger ages and have significantly (P<0.05) higher incidence rates. Differences were greatest at younger ages: the <15 year male/female rate ratio for all subtypes combined being 2.2 (95% CI 1.3-3.4). These gender differences impacted on prevalence; most subtype estimates being significantly (P<0.05) higher in males than females. Outcome varied widely by subtype; survival of patients with nodular lymphocyte predominant Hodgkin lymphoma approached that of the general population, whereas less than a third of those with other B-cell (e.g., mantle cell) or T-cell (e.g., peripheral-T) lymphomas survived for ≥5 years. No males/female survival differences were detected. CONCLUSIONS: Major strengths of our study include completeness of ascertainment, world-class diagnostics and generalisability. The marked variations demonstrated confirm the requirement for 'real-world' data to inform aetiological hypotheses, health-care planning and the future monitoring of therapeutic changes.

The health perspectives of Australian adolescents from same-sex parent families: a mixed methods study.

BACKGROUND: Research involving adolescents from same-sex parent families provides an important contribution to the evidence base on their health, well-being and the impact of stigma. To date reports on the perspectives of adolescents with same-sex attracted parents have been limited. This study aimed to describe the multidimensional experiences of physical, mental and social well-being of adolescents living in this context. METHODS: A mixed methods study of adolescents with same-sex attracted parents comprising of an adolescent-report survey of 10- to 17-year-olds and family interviews with adolescents and their parents. Data were collected in 2012 and 2013 as part of the Australian Study of Child Health in Same-Sex Families. RESULTS: The findings from qualitative interviews with seven adolescents and responses to an open-ended survey question (n = 16) suggest four themes: perceptions of normality, positive concepts of health, spheres of life (including family, friends and community) and avoiding negativity. The quantitative sample of adolescents with same-sex attracted parents (n = 35) reported higher scores than population normative data on the dimensions general health and family activities within the Child Health Questionnaire (CHQ) as well as higher on the peer problems scale on the Strengths and Difficulties Questionnaire (SDQ). Perceived stigma correlates with lower health and well-being overall. CONCLUSIONS: Positive health outcomes are informed by the ways adolescents conceptualize health and how they construct their spheres of life. Peer relationships, and community perspectives of same-sex families, inform perceived stigma and its correlation with poorer health and well-being. Although adolescents see their families as essentially normal they are negatively affected by external societal stigma.

Surgical management of labral tears during femoroacetabular impingement surgery: a systematic review.

PURPOSE: This systematic review explored reported outcomes addressing femoroacetabular impingement (FAI), specifically those comparing labral debridement to labral repair. In addition, the quality of the evidence was evaluated for the purposes of making treatment recommendations. METHODS: Three databases (MEDLINE, EMBASE, and PubMed) were searched for comparative studies involving labral repair and debridement during FAI surgery. Two reviewers conducted a title, abstract, and full-text review of eligible studies and the references of these studies. Inclusion and exclusion criteria were applied to the searched studies, data were extracted, and a quality assessment was completed for included studies. RESULTS: Six eligible studies involving 490 patients were identified. The most commonly reported outcome measure was the modified Harris hip score (MHHS) (50 %). All studies reported that labral repair had greater postoperative improvements in functional scores (modified Harris hip, non-arthritic hip, hip outcome, and Merle d'Aubigne scores) compared to labral debridement. Five studies reported statistically significant improvements with labral repair. MHHS were pooled to demonstrate a clinically important difference in favor of labral repair by 7.4 points in three studies. The mean individual study quality can be considered fair. However, the overall quality of the body of evidence in this review is rated as low according to GRADE guidelines. CONCLUSIONS: This review demonstrates a reporting of better clinical outcomes with labral repair compared to labral debridement in all studies with five of six studies reporting statistically significant improvements (of repair over debridement). However, given the lack of high quality evidence and associated limitations in study design, these results should be interpreted with caution. Consequently, definitive treatment recommendations require further investigation with well-conducted clinical trials. This systematic review enables the discussion of best evidence practice for the surgical managing of a labral tear associated with FAI. LEVEL OF EVIDENCE: III.

Results of the PeRception of femOroaCetabular impingEment by Surgeons Survey (PROCESS).

PURPOSE: Currently, there is a lack of high-level evidence addressing the variety of treatment options available for patients diagnosed with femoroacetabular impingement (FAI). The objective was to determine the current state of practice for FAI in Canada. METHODS: A questionnaire was developed and pretested to address the current state of knowledge among orthopaedic surgeons regarding FAI treatment using a focus group of experts, reviewing prior surveys, and reviewing online guidelines addressing surgical interventions for FAI. The membership of the Canadian Orthopaedic Association (COA) was surveyed through email and mail in both French and English. RESULTS: Two hundred and two surveys were obtained (20 % response rate), of which 74.3 % of respondents manage patients under age 40 with hip pain. Most surgeons (62 %) considered failure of non-operative management as the most important indication for the surgical management of FAI, usually by treating both bony and soft tissue damage (54.4 %). The majority of surgeons were unsure of the existence of evidence supporting the best clinical test for FAI, the use of a diagnostic intra-articular injection for diagnosis of FAI, and for non-operative management of FAI. One in four respondents supported a sham surgery (24.8 %) control arm for a trial evaluating the impact of surgical intervention on FAI. CONCLUSIONS: This survey elucidates areas of research for future studies relevant to FAI and highlights controversial areas of treatment. The results suggest that the current management of FAI by members of the COA is limited by a lack of awareness of high-level evidence.

Radiographic prevalence of CAM-type femoroacetabular impingement after open reduction and internal fixation of femoral neck fractures.

PURPOSE: The purpose of this study was to estimate the radiographic prevalence of CAM-type femoroacetabular impingement (FAI) in elderly patients (≥ 50 years) who have undergone internal fixation for femoral neck fracture. METHODS: A total of 187 frog-leg lateral radiographs of elderly patients who underwent internal fixation for a femoral neck fracture were reviewed by two independent reviewers. The alpha angle, beta angle, and femoral head-neck offset ratio were calculated. The presence of two abnormal radiographic parameters was deemed to be diagnostic of radiographic CAM-type impingement. RESULTS: Radiographic CAM-type FAI was identified in 157 out of 187 (84 %) patients who underwent internal fixation for fractures of the femoral neck. Moderate-to-good inter-observer reliability was achieved in the measurement of radiographic parameters. With reference to fracture subtypes and prevalence of radiographic features of CAM-type morphology, 97 (72 %) out of 134 patients were positive for CAM in Garden subtypes I and II, whereas 49 (85.9 %) out of 57 patients had radiographic CAM in Garden III and IV subtypes. CONCLUSION: There was a high prevalence of CAM-type FAI in patients that underwent surgical fixation of femoral neck fractures. This is significantly higher than the reported prevalence in non-fracture patient populations. The high prevalence of CAM morphology could be related to several factors, including age, fracture morphology, quality of reduction, type of fixation, and fracture healing.

'Closing the gap': Evaluating the success of non-mandatory strategies for influenza vaccination of Victorian healthcare workers.

INTRODUCTION: While annual influenza vaccination of healthcare workers (HCWs) is recommended, uptake is often suboptimal. We sought to evaluate influenza vaccination uptake by HCWs in Victorian public healthcare facilities, where non-mandatory programs are used. METHODS: All participating facilities completed an annual survey (2014-2019) recording HCW influenza vaccination status. Uptake in high-risk departments (emergency and intensive care units) was evaluated for the 2019 season. RESULTS: The proportion of vaccinated HCWs increased annually, from 72.2% (2014) to 87.7% (2019), with pre-set targets generally achieved. In 2019, 110,324 HCWs in 107 facilities were vaccinated (87.7%). Of those without documented vaccination, 7591 (6.0%) declined and 7906 (6.3%) had unknown status. Uptake was higher in high-risk departments (91.4%). CONCLUSION: Increasing annual influenza vaccination uptake by HCWs in Victorian public healthcare facilities has been achieved in the context of performance monitoring targets. Small proportions declined or had unknown status. Future policies should focus on these HCWs.

Estimation of the impact of genital warts on health-related quality of life.

OBJECTIVES: One of the two new human papillomavirus (HPV) vaccines protects against HPV types 6 and 11, which cause over 95% of genital warts, in addition to protecting against HPV types 16 and 18. In anticipation of HPV vaccine implementation, the impact of genital warts on health-related quality of life (HRQoL) was measured to assess the potential benefits of the quadrivalent over the bivalent vaccine. METHODS: Genitourinary medicine clinic patients aged 18 years and older with a current diagnosis of genital warts were eligible; 81 consented and were interviewed by a member of the research team. A generic HRQoL questionnaire, the EQ-5D (comprising EQ-5D index and EQ visual analogue scale (VAS) scores) and a disease-specific HRQoL instrument, the CECA10, were administered. Previously established UK population norms were used as a control group for EQ-5D comparisons. RESULTS: Cases (with genital warts) had lower EQ VAS and EQ-5D index scores than controls. After adjusting for age a mean difference between cases and controls 30 years of age and under (n = 70) of 13.9 points (95% CI 9.9 to 17.6, p<0.001) for the EQ VAS and 0.039 points (95% CI 0.005 to 0.068, p = 0.02) on the EQ-5D index (also adjusted for sex) was observed. The difference between cases and controls for the EQ VAS was especially notable in young women. CONCLUSIONS: Genital warts are associated with a significant detriment to HRQoL. The potential added benefit of preventing most cases of genital warts by HPV vaccination should be considered in decisions about which HPV vaccine to implement in the United Kingdom.

Acquired abnormalities of polymorphonuclear neutrophil function.

Normal polymorphonuclear neutrophils (PMN) in the circulation are resting cells expressing small numbers of low affinity receptors. During inflammation they are upregulated to increase expression of high affinity receptors and discharge both primary and secondary granules. This is reflected by a pattern of changes which can be detected in PMN from the circulation of patients with infection, trauma or burns. Different patterns of abnormality occur in patients with systemic disease and increased risk of infection such as diabetes and renal failure. Functional defects also occur in PMN from patients with acquired blood disorders. It is likely that PMN contribute to tissue damage in inflammatory and vascular diseases so that drugs which modulate PMN function will be of future therapeutic benefit.

The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity.

Adenosine triphosphate (ATP) bioluminescence was used to determine whether there was a linear relationship between cultured cell number and measured luminescence using the luciferin-luciferase reaction. In all the cells tested including peripheral blood mononuclear cells (MNC), MOLT-4, HL-60, TF-1, NFS-60 and L-929 cell lines there was a significant correlation as determined by Spearman's rank correlation coefficient (p > 0.00001). These observations were then used to determine whether ATP bioluminescence could be used as a suitable substitute for tritiated thymidine uptake as a measure of cell proliferation. The cell lines MOLT-4, HL-60, TF-1 and NFS-60 showed a strong correlation between thymidine uptake and ATP bioluminescence (p > 0.00001 for all cell types). Additionally the ATP method could detect the cytokine dependent proliferation on TF-1 and NFS-60 cells by granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) respectively. The tumour necrosis factor alpha (TNF)-induced cytotoxic effect on L-929 cells could also be accurately detected using this method. It would therefore appear to be possible to use ATP bioluminescence in the detection of cytokine activity in a number of different bioassays.

Measurement of the ADP:ATP ratio in human leukaemic cell lines can be used as an indicator of cell viability, necrosis and apoptosis.

In this study the relative levels of ADP and ATP have been measured in cells undergoing apoptosis. Using HL60, CEM7, Jurkat and U937 cell lines and cytotoxic agents known to induce apoptosis, there was a significant correlation (P<0.01 for all models) between the ADP:ATP ratio and the degree of apoptosis measured by TUNEL and estimation of the sub G(0) fraction by propidium iodide staining and flow cytometry. The ratio measured in viable proliferating cells was found to be less than 0.11 compared with ratios between 0.11 and 1.0 seen in cells undergoing apoptosis. The higher the percentage of hypodiploidy the greater the ratio. Necrosis induced by heat shock resulted in ADP:ATP ratios in excess of 15.0. When primary cultures of AML blast cells were used, there was again a significant correlation between the ADP:ATP ratio and the degree of hypodiploidy. Recent evidence suggests that apoptosis is accompanied by opening of the mitochondrial permeability pores, leading to disruption of the mitochondrial transmembrane potential (DeltaPsi(m)). This results in caspase activation due to the release of cytochrome c and apoptogenic factors into the cytosol. In five experiments using CEM7 and dexamethasone the mitochondrial transmembrane potential was assessed using the fluorescent cyanine dye JC-1 and flow cytometry. Functioning mitochondria concentrate the JC-1 to produce red fluorescence. Loss of mitochondrial transmembrane potential results in green fluorescence only. The percentage of cells exhibiting red fluorescence correlated positively with the ATP values and negatively with the ADP:ATP ratio.

Low-dose lansoprazole provides greater relief of heartburn and epigastric pain than low-dose omeprazole in patients with acid-related dyspepsia.

AIM: To compare the relative efficacies of lansoprazole 15 mg o.m. and omeprazole 10 mg o.m. in relieving heartburn and epigastric pain in patients with acid-related dyspepsia. In addition, the study compared the safety profiles of the two treatments. METHODS: This double-blind, parallel group, randomised, multicentre study was conducted in 52 general practices in the UK. A total of 609 patients was recruited, 562 of whom were eligible for inclusion in the intention-to-treat analysis. All of the patients had experienced at least mild heartburn or mild epigastric pain persistently on at least 4 of the previous 7 days; patients with severe symptoms were excluded. 283 patients received lansoprazole 15 mg and 279 received omeprazole 10 mg, both for 4 weeks. The main efficacy measure was relief of symptoms, based on physician assessments. RESULTS: In the intention-to-treat population, a complete relief of overall primary symptoms of dyspepsia was achieved after 2 weeks in 53% of patients receiving lansoprazole and in 41% of patients receiving omeprazole (P = 0.007). After 4 weeks, 59% of the lansoprazole group and 51% of the omeprazole group had achieved complete symptom relief (P = 0. 078). Antacids were taken for additional relief of symptoms in fewer patients given lansoprazole compared to the omeprazole group in the third and fourth weeks (P = 0.035) and also significantly fewer antacids were taken by patients in the lansoprazole group compared with patients in the omeprazole group (P = 0.033). The proportion of patients reporting adverse events was similar in both groups. CONCLUSION: Low-dose lansoprazole is more effective than low-dose omeprazole in the treatment of patients with mild heartburn or epigastric pain in general practice.

Lansoprazole is superior to ranitidine as maintenance treatment for the prevention of duodenal ulcer relapse.

AIM: To compare lansoprazole 30 mg once daily, lansoprazole 15 mg once daily and ranitidine 150 mg once nightly in the prevention of duodenal ulcer relapse in patients whose duodenal ulcers had been previously healed with lansoprazole 30 mg once daily or ranitidine 300 mg nightly. METHODS: A double-blind, parallel group, randomized multicentre study conducted in 33 centres in the UK, Eire, Sweden and Australia. Two hundred and nineteen patients with a duodenal ulcer were randomized to receive lansoprazole 30 mg and 217 to receive ranitidine 300 mg for 8 weeks. Patients were then re-randomized to receive lansoprazole 30 mg (122 patients), lansoprazole 15 mg (121 patients) or ranitidine 150 mg (116 patients) for 12 months. All patients had an endoscopically-proven duodenal ulcer at baseline and were considered suitable for long-term maintenance therapy to prevent relapse. RESULTS: Significantly more patients were healed on lansoprazole (98%) compared to ranitidine (89%) (P < 0.001, Fisher's exact test). Lansoprazole provided more rapid symptom relief than ranitidine. Lansoprazole 30 mg and lansoprazole 15 mg increased the probability of not relapsing in comparison to ranitidine (P = 0.001 and 0.06, respectively, life-table analysis). Relapse rates over the 12 months were lower in the lansoprazole treatment groups (lansoprazole 30 mg, 5%; lansoprazole 15 mg, 12%; and ranitidine, 21%; lansoprazole 30 mg vs. ranitidine 150 mg, P = 0.002). Symptoms were well controlled in both groups during the maintenance phase. All treatments were well tolerated with no major differences seen in adverse event profiles between treatment groups. CONCLUSIONS: Both doses of lansoprazole (30 mg and 15 mg) were superior to ranitidine 150 mg in the prevention of duodenal ulcer relapse. Lansoprazole was superior to ranitidine in terms of symptom control and duodenal ulcer healing. Both treatments were well tolerated.

Kinetic study of Berthelot reaction steps in the absence and presence of coupling reagents.

Several reaction steps in the Berthelot reaction for the determination of ammonia have been separately studied. A reaction order of two has been confirmed for the reaction between HOCl and NH(3). The rate constant for this reaction has been determined to be 3.2 x 10(6)l.mole(-1).sec(-1). The first evidence for the formation of benzoquinonechlorimine is presented. Pentacyanoferrate coupling reagents which accelerate the production of indophenol have been found to operate on the reaction between NH(2)Cl and phenol. The rate constant for the final step of the reaction sequence has been determined to be 5.3 x 10(-3)l.mole(-1).sec(-1). A reaction between chlorimine and pentacyanoferrate compounds has been found to be responsible for the formation of a green product in the presence of excess of coupling reagent.

Computer control of microprocessor-based instruments by keypad emulation.

A keypad emulation method for controlling microprocessor-based instruments by laboratory microcomputers is presented. It is applicable to instruments that use "polled" keypad arrays; the instrument can be controlled by the laboratory computer or operated independently by manual keypad entry. To illustrate the approach, a microprocessor-based HPLC solvent-delivery system was controlled by a laboratory microcomputer which synchronized and sequenced the entire HPLC experiment, including solvent delivery, valve control for column switching and back-flushing, data-acquisition, and dataprocessing.

Sexual health. 2: An overt approach to sexual health education.

An individual's sexuality is not always understood and recognized by healthcare workers. Some nurses have conservative and rigid attitudes regarding sexuality and undertake nursing interventions that may have a detrimental effect on a client's sexual health. If nurses are to take a responsible approach to their nursing interventions they need to reflect upon their knowledge, skills and understanding in relation to their own sexuality and the sexuality of others, and identify ways of rectifying shortfalls. The first of this two-part article discussed issues relating to sexuality in health care (Vol 8(9): 601-6). This part will use a sexual health model to highlight nurses' learning needs. Nurse educators need to include sexual health more overtly within the curriculum. It is important that nurses do not try to be sexual counsellors. Nurses need to acknowledge their limitations and the harm that inappropriate interventions can produce. If sexual health is to be included in nursing curricula, it should not be trivialized. A planned progressive model is required which acknowledges that the human condition is diverse and individual.

Sexual health. 1: Sexuality and nurses' role in sexual health.

This article, the first of two, looks at the issue of sexuality in health care. Sexuality underpins much of what a person is and has significance in everyone's life. Through sexuality, people express their most intimate feelings of individuality and their need for emotional closeness with other human beings. Sexuality is not just about sexual intercourse, it is about the concept of people as men and women--about their manliness or femininity. Sexuality also affects the way people see themselves or would like to be seen, their appearance and behaviour, and their desire to attract those who matter to them. It is about the fears and fantasies people have about themselves and others. Nurses need to have an understanding of sexuality as they may have a crucial part to play in its dynamic progress.