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Introduction The objectives of our study were to identify factors contributing to false-negative Papanicolaou (Pap) tests in patients with endocervical adenocarcinoma (EA) or adenocarcinoma in situ (AIS), and to analyze the impact of educational instruction on interobserver agreement in these cases. Materials and methods False-negative Pap tests from patients with EA/AIS were reviewed by a consensus group and by 12 individual reviewers in 2 rounds, with an educational session on glandular neoplasia in Pap tests conducted between the 2 rounds. Results Of 79 Pap tests from patients with EA/AIS, 57 (72.2%) were diagnosed as abnormal and 22 (27.8%) as negative. Of the 22 false-negative cases, 10 remained negative on consensus review, with false-negative diagnoses attributed to sampling variance. The other 12 cases were upgraded to epithelial abnormalities (including 8 to glandular lesions). The false-negative diagnoses were attributed to screening variance in 2 cases and interpretive variance in 10 cases. On individual review, abnormal cells were misinterpreted as reactive glandular cells or endometrial cells in 7 of 8 and 5 of 8 cases upgraded to glandular abnormalities, respectively. With education, the proportion of individual reviewers demonstrating at least moderate agreement with the consensus diagnosis (Cohen’s kappa >0.4) increased from 33% (4 of 12) to 75% (9 of 12). Conclusions Sampling and interpretive variance each accounted for nearly one-half of the false-negative Pap tests, with underclassification as reactive glandular or endometrial cells the main source of the interpretive variances. Educational instruction significantly decreased the interpretive variance and interobserver variability in the diagnosis of glandular abnormalities.

Many laboratories rescreen Papanicolaou test slides initially interpreted as negative, but positive for human papillomavirus (HPV) high-risk types, as a quality control measure. We have evaluated the utility of this practice in the era of HPV genotyping as a laboratory improvement project.Between August 2016 and October 2019, we identified 3618 rescreened Papanicolaou tests with follow-up biopsies. The biopsy results were put into 3 groups: 1) Negative; 2) LSIL: HPV changes or low-grade squamous intraepithelial lesion; and 3) HSIL: high-grade squamous intraepithelial lesion or carcinoma. HPV molecular testing results with subtyping for types 16 and 18 were available for 3117 of these cases.A total of 530 of 2812 Papanicolaou tests (18.8%) with positive HPV results were reinterpreted as cytologically abnormal after rescreening; 75 (14.2%) had a biopsy result of HSIL. The subset positive for HPV types 16/18 had 38 of 133 cytology positive cases diagnosed as HSIL on biopsy vs. 107 of 935 cytology negative cases diagnosed as HSIL on biopsy (28.6% vs. 11.4%, P0.0001). The subset positive for "other" (non-16/18) high-risk HPV types had 37 of 397 cytology positive follow-up HSIL vs. 84 of 1288 cytology negative follow-up HSIL (9.3% vs. 6.5%, P = 0.075).Rescreening has the highest yield in specimens positive for types 16/18. However, for this group colposcopy is recommended regardless of cytology findings, reducing the patient benefit. Routine rescreening of cytology negative/HPV positive Papanicolaou tests has reduced utility when HPV subtyping is performed and should be reconsidered.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE. Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab’s effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.

Background/Aims The COVID-19 pandemic has resulted in unprecedented changes to healthcare services. This study aimed to evaluate the impact of the COVID-19 pandemic on referrals to cardiology services in a tertiary hospital. Methods Royal Stoke University Hospital has a cardiac assessment nurse team that provides rapid access to specialist cardiology opinion. All referrals are recorded on a database, which was used to determine how COVID-19 affected the number and types of referrals to cardiology during March–September 2019 and March–September 2020. Results A total of 12 447 referrals were made to the cardiac assessment nurse teams over the evaluation period. Compared to the average number of referrals across all months, there was a decline of 10.5%, 31.2% and 18.5% during March, April and May 2019 respectively. Comparing 2020 to 2019, there were more 999 calls (17.7% vs 15.7%) and accident and emergency referrals (46.5% vs 45.0%), and fewer interhospital referrals (16.0% vs 19.6%). In terms of advice provided for the 999 referrals, a greater number were advised to go to the accident and emergency department (10.5% vs 0%) and direct phone advice provided to those in other settings increased (11.7% vs 0.1%) in 2020. Conclusions The COVID-19 pandemic was associated with a reduction in the number of overall referrals to cardiology, while also demonstrating a shift towards more advice to attend the accident and emergency department for assessment or direct phone advice being provided about management in the community.

Objective Adipose tissue plays a key role in obesity-related metabolic dysfunction. MicroRNA (miRNA) are gene regulatory molecules involved in intercellular and inter-organ communication. It was hypothesized that miRNA levels in adipose tissue would change after gastric bypass surgery and that this would provide insights into their role in obesity-induced metabolic dysregulation. Methods miRNA profiling (Affymetrix GeneChip miRNA 2.0 Array) of omental and subcutaneous adipose (n = 15 females) before and after gastric bypass surgery was performed. Results One omental and thirteen subcutaneous adipose miRNAs were significantly differentially expressed after gastric bypass, including downregulation of miR-223-3p and its antisense relative miR-223-5p in both adipose tissues. mRNA levels of miR-223-3p targets NLRP3 and GLUT4 were decreased and increased, respectively, following gastric bypass in both adipose tissues. Significantly more NLRP3 protein was observed in omental adipose after gastric bypass (P = 0.02). Significant hypomethlyation of NLRP3 and hypermethylation of miR-223 were observed in both adipose tissues after gastric bypass. In subcutaneous adipose, significant correlations were observed between both miR-223-3p and miR-223-5p and glucose and between NLRP3 mRNA and protein levels and blood lipids. Conclusions This is the first report detailing genome-wide miRNA profiling of omental adipose before and after gastric bypass, and it further highlights the association of miR-223-3p and the NLRP3 inflammasome with obesity.

Background and Aims Lupus nephritis (LN) is the most common severe manifestation of systemic lupus erythematosus (SLE), occurring in up to 40% of patients (pts) with SLE over their disease course, and resulting in 10–20% of pts progressing to end-stage kidney disease.1-3 The BLISS-LN (GSK Study BEL114054; NCT01639339) study demonstrated that the addition of intravenous (IV) belimumab (BEL) to standard therapy (ST) in pts with active LN significantly improved renal responses over 2 years compared with ST alone.4 Here we present additional safety and efficacy data from the 6-month open-label (OL) extension phase of BLISS-LN. Method In this OL phase, eligible completers of the Phase 3 BLISS-LN study (those who received BEL or placebo [PBO] through Week 100 and completed Week 104 assessments) received BEL 10 mg/kg IV plus ST every 28 days for 24 weeks. Endpoints at OL Week 28 included: safety; Primary Efficacy Renal Response (PERR; defined as urine protein:creatinine ratio [uPCR] ≤0.7; eGFR no more than 20% below OL baseline value or ≥60 ml/min/1.73m2; no rescue therapy); Complete Renal Response (CRR; defined as uPCR Results Of 257 pts (57.4 % of pts in BLISS-LN double-blind [DB] study) screened and enrolled, 255 pts were treated (safety population: 123 pts switched from PBO to BEL; 132 pts remained on BEL). In total, 254 pts were included in the efficacy analyses (PBO to BEL: 122 pts; BEL to BEL: 132 pts). Mean (standard deviation) age was 35.9 (10.3) years. In total, 3.5% of pts withdrew from the OL phase, mainly due to adverse events (AE; 2.0%). Overall, 168/255 (65.9%) pts experienced ≥1 AE (76/123 [61.8%] PBO to BEL pts; 92/132 [69.7%] BEL to BEL pts); 49/255 (19.2%) pts had ≥1 treatment-related AE (25/123 [20.3%] PBO to BEL pts; 24/132 [18.2% ] BEL to BEL pts); 15/255 (5.9%) pts had ≥1 serious AE (5/123 [4.1%] PBO to BEL pts; 10/132 [7.6%] BEL to BEL pts); and 1 death was reported in the PBO to BEL group. The proportion of patients achieving PERR and CRR increased from OL baseline to OL Week 28 in both groups (Table). The median (interquartile range [IQR]) for uPCR and eGFR were maintained from OL baseline through to OL Week 28 (Table). The proportion of SLEDAI score 0) was experienced by 7 (2.9%) pts (4 [3.3%] PBO to BEL; 3 [2.5%] BEL to BEL) compared with OL baseline. There was no appreciable change in the number of patients receiving average daily prednisone-equivalent doses of ≤5 mg or ≤7.5 mg from OL baseline to OL Week 28 (Table). Conclusion BEL was well tolerated as an add-on to ST, with no new safety signals. Efficacy among pts with LN randomised to BEL during the DB phase was maintained during the OL phase. Study funding GSK. Editorial assistance (GSK-funded): Olga Conn, PhD, Fishawack Indicia Ltd., part of Fishawack Health, UK.

BackgroundBetween 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. Lateral flow tests were offered to all people aged over 10 years living, studying or working in the area.MethodsWe conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive test (cases) and a sample of negatives (controls). Population attributable fractions (PAF) were calculated for factors with significantly increased odds following multivariate analysis.ResultsA total of 199 cases and 2,621 controls were recruited by SMS (response rates: 27.1% and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR: 3.39, 95% CI: 1.43-8.03), social care (aOR: 2.63, 95% CI: 1.22-5.67) or healthcare (aOR: 2.31, 95% CI: 1.29-4.13), live with someone self-isolating due to contact with a case (aOR: 3.07, 95% CI: 2.03-4.62), visit a pub (aOR: 2.87, 95% CI: 1.11-7.37), and smoke or vape (aOR: 1.54, 95% CI: 1.02-2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (PAF: 0.2).ConclusionInfection prevention and control should be strengthened to help reduce household transmission. As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.What is already known on this subject?Certain populations are known to be at risk of severe COVID-19: Older people, males, people in minority ethnic groups, people with pre-existing chronic disease or disability, and people in certain public-facing occupations. However, limited information exists on the factors associated with acquiring SARS-CoV-2 in the community.What this study adds?This study provides an insight into the most important factors determining community transmission of SARS-CoV-2. We found that transmission within the household was the most important source of SARS-CoV-2 infection. Working in the hospitality sector, and visiting the pub were associated with infection but at the time of this study were relatively infrequent exposures. Smoking or vaping had a small but significant effect. Working in education, living with someone working in education, having caring responsibilities, attending a healthcare appointment and visiting a supermarket, restaurant, gym or leisure centre were not associated with infection. Whilst these findings relate to a specific community at a specific time in the course of the epidemic when social restrictions were in place, the information will be useful in supporting policy decisions. Mass testing exercises present an opportunity to conduct epidemiological studies to gather information to inform the local and national epidemic response.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019 and became a pandemic in a short period of time. While most infected people might have mild symptoms, older people and people with chronic illnesses may develop acute respiratory distress syndrome (ARDS). Patients with ARDS with worsening hypoxemia require prone positioning to improve the respiratory mechanics and oxygenation. Intubated patients may stay in a prone position up to 12–16 h, increasing the risk of pressure injury (PI). Frequent skin inspections and PI risk assessment in COVID-19 patients will be challenging due to hospital infection control measures aimed to reduce the risk for health professionals. In this perspective article, we summarize the best practice recommendations for prevention of PI in SARS-CoV-2-infected ARDS patients in prone positioning. Prior to positioning patients in prone position, the main recommendations are to (1) conduct a skin assessment, (2) use pressure redistribution devices, (3) select an appropriate mattress or an overlay, (4) ensure that the endotracheal tube securing device is removed and the endotracheal tube is secured with tapes, (5) use a liquid film-forming protective dressing, and (6) lubricate the eyes and tape them closed. Once a patient is in prone position, it is recommended to (1) use the swimmer's position, (2) reposition the patient every 2 h, and (3) keep the skin clean. When the patient is repositioned to supine position, healthcare professionals are advised to (1) assess the pressure points and (2) promote early mobilization.

Pressure injury is a common hospital acquired complication across the globe. The severity of hospital acquired pressure injury ranges from skin redness and no skin breakdown to full skin and tissue loss, exposing tendons and bones. Pressure injury can significantly impact on quality of life. In addition to the human cost, hospital acquired pressure injury carries a high economic burden with the cost of treatment far outweighing preventative measures. Hospital acquired pressure injury rates are a key indicator of health services performance. Globally, health care services aim to reduce its incidence. In Australia, the federal health minister has prioritised the need for improvement in hospital acquired pressure injury surveillance and prevention. Capacity building is vital to optimise pressure injury surveillance and prevention in acute care services. In this perspective article, we provide a framework for capacity building to optimise hospital acquired pressure injury prevention and surveillance in a large cross-sector collaborative partnership in Australia. This framework comprises six key action areas in capacity building to optimise pressure injury outcomes, this include: research, organizational development, workforce development, leadership, collaboration, and consumer involvement.

Background Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between baseline BLyS mRNA/protein levels and/or type 1 IFN-inducible gene signature (IFN-1) and responses to the BLyS-targeting monoclonal antibody belimumab in SLE. Methods In BLISS-52 and BLISS-76, patients with autoantibody-positive SLE and a SELENA-SLEDAI score ≥ 6 and receiving stable standard SLE therapy were randomised to intravenous belimumab 10 mg/kg or placebo, plus standard of care (SoC), for 52 or 76 weeks. For this post hoc meta-analysis, patients with an appropriate mRNA sample were stratified by BLyS mRNA expression (tertiles: high/medium/low; revised quantiles: high/low), IFN-1 mRNA expression (high/low) and BLyS protein level (high/low). Co-primary endpoints were correlation between baseline BLyS and IFN-1 mRNA levels and SLE Responder Index (SRI)4 response at week 52 within BLyS/IFN-1 subgroups. Secondary endpoints included time to first severe SELENA-SLEDAI Flare Index (SFI) flare. Results Of 554 patients included in this analysis, 281 had received belimumab and 273 had received placebo. Baseline BLyS and IFN-1 mRNA levels were highly correlated (Spearman’s rank correlation coefficient 0.7799; 95% confidence interval [CI] 0.7451, 0.8106; p p = 0.0153), high BLyS mRNA quantile (OR 1.58; 95% CI 1.02, 2.44; p = 0.0402), high IFN-1 mRNA (OR 1.58; 95% CI: 1.08, 2.31; p = 0.0186) and high BLyS protein (OR 3.57; 95% CI 1.63, 7.83; p = 0.0015) subgroups only. The risk of severe SFI flare was significantly lower with belimumab than placebo in the high BLyS mRNA quantile (hazard ratio [HR] 0.59; 95% CI 0.36, 0.97; p = 0.0371) and high BLyS protein (HR 0.39; 95% CI 0.19, 0.79; p = 0.0090) subgroups. Conclusions This post hoc meta-analysis demonstrated a tendency towards improved response to add-on intravenous belimumab 10 mg/kg versus SoC alone in patients with high baseline BLyS protein and IFN-1 mRNA levels and medium/high BLyS mRNA levels.

Background:BLISS-LN (GSK Study BEL114054; NCT01639339), the largest lupus nephritis (LN) study to date, showed that intravenous (IV) belimumab (BEL) + standard therapy (ST) improved outcomes compared with ST alone in patients (pts) with active LN.1Objectives:To assess additional safety and efficacy data of BEL + ST in pts with LN in a 6-month open-label (OL) phase beyond 2 years of double-blind (DB) treatment in BLISS-LN.Methods:In this OL phase, eligible completers of the DB phase received monthly BEL 10 mg/kg IV + ST for 6 months. Endpoints: safety; Primary Efficacy Renal Response (PERR; uPCR ≤0.7; eGFR no worse than 20% below OL baseline eGFR or ≥60 ml/min/1.73 m2; no prohibited medications) and Complete Renal Response (CRR; uPCR 2; no prohibited medications) at OL Week 28; proportion of pts with SLEDAI score Results:We enrolled 257 pts (57.4% of pts in BEL114054) and treated 255 pts. All treated pts were included in the safety population (123 pts switched from placebo [PBO] to BEL; 132 pts remained on BEL). Efficacy was assessed in the safety population, excluding 1 pt due to non-compliance (mITT population; PBO to BEL: 122 pts; BEL to BEL: 132 pts). 96.5% of pts completed the OL phase; 3.5% withdrew, mainly due to adverse events (AE; 2.0%).Overall, 168/255 (65.9%) pts had ≥1 AE (76/123 [61.8%] PBO to BEL pts; 92/132 [69.7%] BEL to BEL pts); 15/255 (5.9%) pts had ≥1 serious AE (5/123 [4.1%] PBO to BEL pts; 10/132 [7.6%] BEL to BEL pts); 1 (0.8%) pt died in the PBO to BEL group.Proportions of PERR and CRR responders increased from OL baseline to OL Week 28 (Table 1. below)Proportions of pts who attained SLEDAI scores In pts with autoantibodies at OL baseline, anti-dsDNA and anti-C1q levels decreased from OL baseline to OL Week 28 in both groups. Among pts with low C3/C4 levels at OL baseline, C3/C4 levels increased from OL baseline to OL Week 28 in both groups (Table 1. below)Conclusion:In this OL phase of BLISS-LN, proportions of PERR and CRR responders increased in both the BEL-naïve and BEL-experienced groups; and no new safety signals were observed. Improvements in biomarker levels were observed, especially in pts who switched from PBO to BEL.Funding:GSK.References:[1]Furie R, et al. N Engl J Med. 2020;383(12):1117-28.Table 1.Responses at OL baseline and OL Week 28 (mITT population, N=254)OL baseline*OL Week 28PBO to BEL(n=122)BEL to BEL(n=132)PBO to BEL(n=122)BEL to BEL(n=132)n122132118122PERR, n (%)73 (59.8)†93 (70.5)†79 (66.9)91 (74.6)CRR, n (%)44 (36.1)†63 (47.7)†57 (48.3)76 (62.3)SLEDAI score n122132120122Responders, n (%)44 (36.1)†64 (48.5)†40 (33.3)64 (52.5)Prednisone-equivalent dosen122132121128≤5 mg, n (%)59 (48.4)78 (59.1)60 (49.6)75 (58.6)≤7.5 mg, n (%)62 (50.8)85 (64.4)66 (54.5)83 (64.8)Anti-dsDNA (IU/ml)‡n85648161Median (IQR) levels107.0 (49.0, 212.0)65.5 (42.5, 126.5)--Median (IQR) % change from baseline---30.2 (-46.3, -6.8)-10.7 (-27.2, 9.1)Anti-C1q (U/ml)§n64605854Median (IQR) levels71.7 (36.6, 167.5)47.1 (33.0, 75.7)--Median (IQR) % change from baseline---23.0 (-41.5, 0.5)-16.5 (-33.0, 6.1)C3 (mg/dl)‖n45374435Median (IQR) levels78.0 (72.0, 83.0)80.0 (71.0, 84.0)--Median (IQR) % change from baseline--6.2 (-4.2, 14.6)4.7 (-4.8, 16.9)C4 (mg/dl)‖n18121811Median (IQR) levels7.5 (6.0, 8.0)7.0 (7.0, 8.5)--Median (IQR) % change from baseline--23.6 (11.1, 37.5)11.1 (0.0, 57.1)*DB Week 104 visit and the OL baseline visit were the same visit; †Post hoc analyses; ‡Among anti-dsDNA positive pts at OL baseline (≥30 IU/ml); §Among anti-C1q positive pts at OL baseline (≥22.2 U/ml); ‖Among pts with low C3 (Acknowledgements:Medical writing assistance was provided by Olga Conn, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Richard Furie Consultant of: GSK, Grant/research support from: GSK, Brad H Rovin Consultant of: GSK, Frederic Houssiau Consultant of: GSK, Grant/research support from: UCB, Gabriel Contreras Consultant of: Genentech, Merck, Grant/research support from: Genentech, Merck, Paula Curtis Shareholder of: GSK, Employee of: GSK, Anuradha Madan Shareholder of: GSK, Employee of: GSK, Angela Jones-Leone Shareholder of: GSK, Employee of: GSK, Mohamed Okily Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

Objective Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. Methods One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. Results One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R2 = 0.57, P = 7.5 × 10-8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. Conclusions This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity.

Pressure injuries (PIs) are a common quality indicator for hospital care, and preventing PIs often requires patient engagement; as such, Australian consensus research has recommended that high-quality education materials be made to patients for PIs via hospital networks. The purpose of the present study was to assess the availability and accuracy of patient education materials on PIs in publicly available hospital websites in Victoria, Australia. Two independent coders assessed 212 websites for content on PI prevention and management, analysing availability and accuracy of PI definitions, risk factors, preventive strategies, referral, visual tools, consumer endorsement, information for family/carers, and translation on community languages. A greater proportion of hospitals did not have any patient education materials on PI prevention publicly available, with private hospitals (compared with public) and metropolitan hospitals (compared to rural) more likely to have materials available on their sites. The available materials contained accurate messages on PI defining characteristics and risk factors for PIs, although there was considerable variability on the availability of other information. Our findings suggest a significant deficit in the availability of educational materials for acute care patients and their families. There is a need for evidence-based, consumer-endorsed, uniform materials on all hospital websites to prevent PIs in acute care.

// Joy M. McDaniel 1, 2 , Katherine E. Varley 3 , Jason Gertz 3 , Daniel S. Savic 1 , Brian S. Roberts 1 , Sarah K. Bailey 4 , Lalita A. Shevde 4, 6 , Ryne C. Ramaker 1, 7 , Brittany N. Lasseigne 1 , Marie K. Kirby 1 , Kimberly M. Newberry 1 , E. Christopher Partridge 1 , Angela L. Jones 1 , Braden Boone 1 , Shawn E. Levy 1 , Patsy G. Oliver 5 , Katherine C. Sexton 6 , William E. Grizzle 6 , Andres Forero 6 , Donald J. Buchsbaum 5 , Sara J. Cooper 1 , Richard M. Myers 1 1 HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA 2 The University of Alabama in Huntsville, Huntsville, AL 35899, USA 3 Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA 4 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA 5 Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA 6 University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA 7 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA Correspondence to: Richard M. Myers, email: rmyers@hudsonalpha.org Keywords: TNBC, STAT3, ChIP-seq, RNA-seq, invasion Received: August 15, 2016 Accepted: November 14, 2016 Published: December 24, 2016 ABSTRACT Breast cancer is a heterogeneous disease comprised of four molecular subtypes defined by whether the tumor-originating cells are luminal or basal epithelial cells. Breast cancers arising from the luminal mammary duct often express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2). Tumors expressing ER and/or PR are treated with anti-hormonal therapies, while tumors overexpressing HER2 are targeted with monoclonal antibodies. Immunohistochemical detection of ER, PR, and HER2 receptors/proteins is a critical step in breast cancer diagnosis and guided treatment. Breast tumors that do not express these proteins are known as “triple negative breast cancer” (TNBC) and are typically basal-like. TNBCs are the most aggressive subtype, with the highest mortality rates and no targeted therapy, so there is a pressing need to identify important TNBC tumor regulators. The signal transducer and activator of transcription 3 (STAT3) transcription factor has been previously implicated as a constitutively active oncogene in TNBC. However, its direct regulatory gene targets and tumorigenic properties have not been well characterized. By integrating RNA-seq and ChIP-seq data from 2 TNBC tumors and 5 cell lines, we discovered novel gene signatures directly regulated by STAT3 that were enriched for processes involving inflammation, immunity, and invasion in TNBC. Functional analysis revealed that STAT3 has a key role regulating invasion and metastasis, a characteristic often associated with TNBC. Our findings suggest therapies targeting STAT3 may be important for preventing TNBC metastasis.

The COVID-19 pandemic led to many European countries imposing lockdown measures and limiting people&rsquo, s movement during spring 2020. During the summer 2020, these strict lockdown measures were gradually lifted while in autumn 2020, local restrictions started to be re-introduced as a second wave emerged. After initial restrictions on visitors accessing many Nature Protected Areas (PAs) in Europe, management authorities have had to introduce measures so that all users can safely visit these protected landscapes. In this paper, we examine the challenges that emerged due to COVID-19 for PAs and their deeper causes. By considering the impact on and response of 14 popular European National and Nature Parks, we propose tentative longer-term solutions going beyond the current short-term measures that have been implemented. The most important challenges identified in our study were overcrowding, a new profile of visitors, problematic behavior, and conflicts between different user groups. A number of new measures have been introduced to tackle these challenges including information campaigns, traffic management, and establishing one-way systems on trail paths. However, measures to safeguard public health are often in conflict with other PA management measures aiming to minimize disturbance of wildlife and ecosystems. We highlight three areas in which management of PAs can learn from the experience of this pandemic: managing visitor numbers in order to avoid overcrowding through careful spatial planning, introducing educational campaigns, particularly targeting a new profile of visitors, and promoting sustainable tourism models, which do not rely on large visitor numbers.

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

OBJECTIVE To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m2, respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety. RESULTS Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m2, HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (−0.83% vs. −0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively. CONCLUSIONS Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy.

OBJECTIVE to evaluate the efficacy and safety of albiglutide compared with placebo and active comparators from an integrated trial subpopulation of Latino/Hispanic patients whose type 2 diabetes mellitus (T2DM) was inadequately controlled on their current regimen of diet and exercise, with or without oral antidiabetic drugs (OADs) and/or insulin. METHODS Latino/Hispanic patient subpopulations (N = 1204) across 7 phase III albiglutide studies (N = 4400) were evaluated post-hoc for efficacy and safety. Comparators were placebo, sulfonylureas, insulin, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors. Glycatedhemoglobin (HbA1c) change from baseline to the time of the primary endpoint assessment (from 26 to 104 weeks) was evaluated in patients on diet and exercise and/or OADs, with or without insulin. Patients were allowed to continue in the study if hyperglycemic rescue was required, according to a prespecified algorithm and at the discretion of the investigator. RESULTS At baseline in the Latino/Hispanic subpopulation, the mean HbA1c was 8.3%, mean age was 53 years, mean body mass index was 32 kg/m2, and mean duration of T2DM was 8.0 years. The primary endpoint of mean HbA1c difference (albiglutide - placebo) was -0.94% for the Latino/Hispanic subpopulation and -0.86% (p

Epistaxis can occur for many different reasons in horses. Determining the source of haemorrhage is crucial to minimise the risk of serious and potentially life-threatening disease going untreated. Owners frequently over-estimate the volume or significance of blood loss, so care should be taken to verify the exact nature and quantity of any blood loss. Common causes include: facial trauma exercise-induced pulmonary haemorrhage (EIPH) idiopathic nasal haemorrhage.

Complementary and alternative medicine (CAM) use is common in patients with cardiovascular disease. Although numerous efforts have sought to understand CAM types and the prevalence of CAM, whether patients preferentially use CAM instead of evidence-based therapies is unknown. Self-reported use of CAM and evidence-based therapies in a prospective registry of hospitalized patients with acute coronary syndrome from March 1, 2001 to October 31, 2002 were examined. Poisson regression models were used to assess whether CAM use was independently associated with lower rates of aspirin, beta-blocker, and statin use in 596 patients with established coronary artery disease (CAD). Overall, CAM use was 19% in patients with CAD. Higher proportions of patients who used CAM were non-Caucasian (31% vs 12%), uninsured (12% vs 7%), economically burdened (58% vs 29%), and had depression (13% vs 6%, p0.05 for all). Patients who used CAM were more likely to use beta blockers (64% vs 46%, p=0.008) and as likely to use aspirin (73% vs 74%, p=0.90) and statins (71% vs 68%, p=0.76) as non-CAM users. Adjusting for demographic and clinical factors did not change results (CAM users: RR 1.27, 95% confidence interval [CI] 1.01 to 1.60 for using beta blockers, RR 0.97, 95% CI 0.85 to 1.11 for using aspirin, and RR 1.05, 95% CI 0.87 to 1.28 for using statins). In conclusion, although CAM users with established CAD have worse socioeconomic status than nonusers, we found no evidence that they were less compliant with evidence-based therapies.

Differentiation between septic arthritis and transient synovitis of the hip in children can be difficult. Kocher et al. recently developed a clinical prediction algorithm for septic arthritis based on four clinical variables: history of fever, non-weight-bearing, an erythrocyte sedimentation rate ofor=40 mm/hr, and a serum white blood-cell count of12000/mm(3) (12.0 x 10(9)/L). The purpose of this study was to apply this clinical algorithm retrospectively to determine its predictive value in our patient population.A retrospective review was performed to identify all children who had undergone a hip arthrocentesis for the evaluation of an irritable hip at our institution between 1992 and 2000. One hundred and sixty-three patients with 165 involved hips satisfied the criteria for inclusion in the study and were classified as having true septic arthritis (twenty hips), presumed septic arthritis (twenty-seven hips), or transient synovitis (118 hips).Patients with septic arthritis (true and presumed; forty-seven hips) differed significantly (p0.05) from patients with transient synovitis (118 hips) with regard to the erythrocyte sedimentation rate, differential of serum white blood-cell count, total white blood-cell count and differential in the synovial fluid, gender, previous health-care visits, and history of fever. If the four independent multivariate predictors of septic arthritis proposed by Kocher et al. were present, the predicted probability of the patient having septic arthritis was 59% in our study, in contrast to the 99.6% predicted probability in the patient population described by Kocher et al. Statistical analyses demonstrated that the best model to describe our patient population was based on three variables: a history of fever, a serum total white blood-cell count of12000/mm(3) (12.0 x 10(9)/L), and a previous health-care visit. When all three variables were present, the predicted probability of the patient having septic arthritis was 71%.Although the use of a clinical prediction algorithm to differentiate between septic arthritis and transient synovitis may have improved the utility of existing technology and medical care to facilitate the diagnosis at the institution at which the algorithm originated, application of the algorithm proposed by Kocher et al. or of our three-variable model does not appear to be valid at other institutions.

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are well-documented disorders causing significant morbidity in the female population. Treatments prescribed do not necessarily reflect proven clinical effectiveness. A recent systematic review from the Exeter Department of Complementary Medicine failed to endorse complementary therapies as a whole for treatment of PMS. However, a recent randomised controlled trial of homeopathic treatment for PMS confirms the clinical experience of homeopathic physicians that homeopathy is helpful in PMS.

Introduction: Smoking rates in pregnant mothers remains unacceptably high despite the use of many different approaches. In South Wales smoking rates in this group remain high despite free access to professional cessation services. The aim of this study was to determine the barriers to smoking cessation. Methods: A questionnaire was administered post-partum to 36 mothers who smoked throughout pregnancy and lived within the NHS Cwm Taf University Health Board catchment area, South Wales, UK. Results: Most mothers (88%) reportedly reduced their daily smoking rate from between 11-15 to less than 10 per day, rather than cease. The majority (78%) did not use a smoking cessation service. The most common reason given for factors which stopped them using cessation services were issues around family support, such as lack of child care. When asked smoking cessation was considered difficult as pregnancy was a stressful time and withdrawal from smoking at this time was deemed to add to the stress. Conclusion: There is no single factor identified that prevent women using professional smoking cessation services, family factors and further stress avoidance associated with quitting smoking were considered the main barriers. Selfhelp methods to quit were considered preferable such as nicotine replacement products. Reducing smoking rather than quitting altogether was seen as the easiest option.

Purpose: To evaluate the safety, efficacy, and results of laparoscopically assisted placement of gastrostomy tubes (LAPGT) and compare the cost with that of percutaneous endoscopic gastrostomy (PEG). Patients and Methods: The medical records of all patients who underwent laparoscopic gastrostomy tube placement (N = 51) either alone (N = 8) or in conjunction with a fundoplication (N = 43) over a 2-year period (1998-1999) were evaluated for complications, length of procedure, and hospital charges. Hospital charges were compared with those of eight randomly selected patients who underwent PEG during the same period. We also reviewed the PEG database over this period to evaluate the percentage of children requiring a second procedure to convert a gastrostomy tube to a low-profile device. Results: There were no major complications related to gastrostomy tube placement in any of the 51 patients who underwent LAPGT. The operative time for LAPGT alone was 45 minutes. The initial hospital charges for LAPGT was $10...

In many clinical settings, providers rely on visual assessment when delivering feedback on CPR quality. Little is known about the accuracy of visual assessment of CPR quality. We aimed to determine how accurate pediatric providers are in their visual assessment of CPR quality and to identify the optimal position relative to the patient for accurate CPR assessment.We videotaped high-quality CPR (based on 2010 American Heart Association guidelines) and 3 variations of poor quality CPR in a simulated resuscitation, filmed from the foot, head and the side of the manikin. Participants watched 12 videos and completed a questionnaire to assess CPR quality.One hundred and twenty-five participants were recruited. The overall accuracy of visual assessment of CPR quality was 65.6%. Accuracy was better from the side (70.8%) and foot (68.8%) of the bed when compared to the head of the bed (57.2%; p0.001). The side was the best position for assessing depth (p0.001). Rate assessment was equivalent between positions (p=0.58). The side and foot of the bed were superior to the head when assessing chest recoil (p0.001). Factors associated with increased accuracy in visual assessment of CPR quality included recent CPR course completion (p=0.034) and involvement in more cardiac arrests as a team member (p=0.003).Healthcare providers struggle to accurately assess the quality of CPR using visual assessment. If visual assessment is being used, providers should stand at the side of the bed.

A retrospective comparison of cancer incidence data and, where relevant, population data with 16 955first-time users (patients, relatives and friends) of a national cancer information service (CancerBACUP) during the period April1995 to March 1996 is presented. The number of events observed was compared with the number of events expected, were the nationalrates of cancer incidence and population demographics apply. Standardized incidence ratios (SIRs) (observed – expectedratios) were used to indicate any differences. Statistically significant differences (P< 0.001) in the observed andexpected sex, age and primary site distribution of patients enquired about were found. Statistically significant differences(P< 0.001) were also identified for the age, employment status, socioeconomic class and geographical location offirst-time enquirers (patients, relatives and friends). Enquiries about brain, testis and breast cancers and non-Hodgkin'slymphoma (NHL) were substantially higher than expected; enquiries about bladder, lung, stomach and colorectal cancers were muchlower than expected. As the service is provided via a freephone number, it is available to all, and users might be expected to berandomly distributed across the variables listed. The underlying reasons for the differences identified need to be investigated,and the role of information in the care of cancer patients should be formally evaluated. © 1999 Cancer Research Campaign

The objective of this paper is to determine if phenobarbital exposure during pregnancy affects developmental outcome at age 2 years. Between 1991 and 1994, 401 pregnant patients at risk for delivery prior to 34 weeks' gestation were invited to participate; 48 mothers declined entry. Before delivery, pharmacy randomized the pregnant women to receive phenobarbital and vitamin K or identically appearing placebo in a blinded fashion. Developmental follow-up at age 2 years was performed. Children from the treatment group scored significantly lower on the Bayley Mental Developmental Index (mean MDI +/- 1 SD) than children whose mothers were randomized to the placebo group [104 +/- 21 (n = 59) vs. 113 +/- 22 (n = 62), p = 0.023]. Of 36 independent variables, randomization group was one of five that individually contributed to the prediction of the Bayley MDI score (p < 0.05). It was concluded that perinatal phenobarbital therapy may impair developmental outcome.

To determine if the glucagon-like peptide-1 (GLP-1) receptor agonist albiglutide, once weekly, impairs counter-regulatory responses during hypoglycaemia.We conducted a randomized, double-blind, parallel, placebo-controlled study in subjects with type 2 diabetes mellitus. A single dose of albiglutide 50 mg (n = 22) or placebo (n = 22) was administered on day 1. Glucose was clamped on day 4 (to coincide with the approximate albiglutide maximum plasma concentration) at 9.0, 5.0, 4.0, 3.3 and 2.8 mmol/l (162, 90, 72, 59.4 and 50.4 mg/dl), with a post-clamp recovery period to 3.9 mmol/l (70 mg/dl). Hormone measurements were made at each plateau and adverse events (AEs) were recorded.The counter-regulatory hormones glucagon, epinephrine, norepinephrine, growth hormone and cortisol were appropriately suppressed when plasma glucose levels were4.0 mmol/l (72 mg/dl), but increased in the albiglutide and placebo groups with glucose levels3.3 mmol/l (59.4 mg/dl) in response to hypoglycaemia. The area under the curve geometric mean ratios (albiglutide : placebo), calculated from the clamped plateau of 4.0 mmol/l (72 mg/dl) to the glucose recovery point, were not significantly different for any of the counter-regulatory hormones. When plasma glucose levels were5.0 mmol/l (90 mg/dl), albiglutide increased pancreatic β-cell secretion of C-peptide in a glucose-dependent manner to a greater extent than did placebo, and it was suppressed in each group when levels were4.0 mmol/l (72 mg/dl). No significant difference between groups was observed in the recovery time to glucose level ≥3.9 mmol/l (≥70 mg/dl). There were no clinically relevant differences in AEs or other safety variables.A single 50-mg dose of albiglutide was well tolerated and did not impair the counter-regulatory response to hypoglycaemia. These data provide mechanistic evidence supporting the low intrinsic hypoglycaemic potential of albiglutide.

Background Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. Methods This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales’ seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Discussion Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it. Electronic supplementary material The online version of this article (doi:10.1186/1471-2458-14-1041) contains supplementary material, which is available to authorized users.

Background Maternal smoking is a key cause of poor health outcomes. In Wales, a third of pregnant women smoke before or during pregnancy, the highest prevalence of maternal smoking in the UK. Supporting women to stop smoking during pregnancy is a challenging area of public health. Models for Access to Maternal Smoking Cessation Support (MAMSS) aimed to examine the effectiveness of smoking cessation in pregnancy services delivered by specially trained practitioners. Methods A non-randomised, quasi-experiment was undertaken across four Health Boards in Wales to assess the effectiveness of new models of service designed to increase the engagement of pregnant women in National Health Service (NHS) stop smoking services. Qualitative approaches were adopted to capture important contextual information and consider multiple perspectives. A flexible, bespoke intervention was offered to pregnant women in intervention sites (delivered by a specialist maternity support worker, a specialist midwife, or a specialist Stop Smoking Wales pregnancy adviser) and compared with usual care delivered by the national stop smoking service. Routine data were collected from maternity records and the NHS Stop Smoking Wales service. The primary outcome was the proportion of smokers who engaged with the service. Power calculations showed that 1168 pregnant smokers were required to detect a 15% difference in the proportion of pregnant smokers engaged with smoking cessation services (5% type I error rate and 90% power). Findings 2756 women were identified by midwifery staff as pregnant smokers (978 in intervention and 1778 in control sites). The proportion of smokers who engaged with the service was significantly higher across intervention sites than control sites. The highest proportion was observed in Health Board area 3, which employed a maternity support worker to support women to quit smoking, where 64 of 181 pregnant smokers (35%, 95% CI 29–43) set a quit date and attended at least one treatment session compared with just two of 227 in usual care (1%, 0–3). This model cost about £500 per engaged smoker. Qualitative findings highlighted the acceptability and feasibility of delivering the service models. Interpretation The maternity support worker model is effective in engaging pregnant women with stop smoking services and has the potential to improve future health outcomes. Funding The research received funding and support in kind from Public Health Wales NHS Trust and the Health Boards involved. Cwm Taf University Health Board's Research and Development department funded their element of the study.

Konstantinos Tziomalos, GerasimosE Krassas, Themistoklis TzotzasDepartment of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki, GreeceAims: To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders.Methods and results: The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality.Conclusions: Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality. Keywords: Sibutramine, obesity, weight loss, cardiometabolic risk factors, obesity-related disorders, side-effects

Thirty-seven patients with carcinoma of the cervix were prospectively staged by examination under anaesthesia (EUA), transvaginal and transrectal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Pathological correlation was available for 20 patients. In the pathologically staged patients, EUA agreed with the staging in 17, understaging three patients. Endosonography agreed with the staging in 19, CT in 16 and MRI in 18 patients. For the remaining 17 patients, endosonography agreed with the EUA findings in 13, CT in 12 and MRI in 12. This study has shown that endosonography and MRI are more accurate than CT in the local staging of carcinoma of the cervix. Computed tomography was least accurate in staging early tumours and differentiating between Stage Ib and IIb disease. Lymph node involvement was detected with equal frequency by both CT and MRI. Magnetic resonance imaging was useful in identifying vaginal and bladder wall involvement and in one patient showed features due to an unsuspected early pregnancy.

The aim of this literature review was to identify the palliative care needs of stroke patients. Stroke results in high levels of mortality and morbidity, yet very little is known about the nature and extent of palliative care services that are available to this patient group, and the ways in which such services could be delivered. A critical review of the international literature found only seven papers that attempted to identify the palliative care needs of patients diagnosed with stroke. The results of the review showed that the preferences of stroke patients and their families in relation to palliative care services are largely unknown. The review also indicated the paucity of data in regard to the distinction between provision of palliative care services for patients who die in the acute phase of stroke and for those patients who die later. Establishing reliable assessments of need are central to designing and implementing effective interventions and further research is required in this area. Further data on how the input of palliative care experts and expertise could be of benefit to patients, and the most effective ways these inputs could be targeted and delivered is required. Palliative Medicine 2007; 21: 323—331

Depression in patients with acute coronary syndrome (ACS) is common and independently prognostic of a higher mortality and worse health status. Despite great attention to its prevalence and prognostic import, little is known about how often hospitalized patients with ACS who have significant depressive symptoms are recognized while receiving routine cardiovascular care.We performed a cross-sectional study of 1181 consecutive patients with confirmed ACS. Detailed reviews of hospital records were performed for the documentation that depressive symptoms were recognized. Multivariable regression analysis was used to identify factors associated with unrecognized depressive symptoms.The prevalence of moderate/severe depressive symptoms was 17.6%. Only 24.5% had documentation that their depressive symptoms were recognized. In multivariable regression analysis, characteristics associated with unrecognized depressive symptoms were race (minorities vs whites; odds ratio [OR] = 6.73, 95% confidence interval [CI] 2.62-19.33), ejection fraction (EF0.40 vs EFor = 0.40; OR = 3.45, 95% CI 1.06-11.23), and education level (no college vs some college; OR = 2.77, 95% CI 1.38-5.69).Despite its prognostic importance and prevalence, moderate to severe depressive symptoms are poorly recognized in hospitalized patients with ACS. Better interventions are warranted to increase the recognition and improve the management of depressive symptoms in patients with ACS.

To investigate the reasons for complaint or non-complaint by rural consumers of health services.Qualitative study using focus group discussion of hypothetical scenarios.Selected rural communities in the Loddon-Mallee region of north-western Victoria.Sixty volunteer participants in eight focus groups recruited through advertising.Issues and themes concerning circumstances leading to, and factors inhibiting, complaints about a health service and awareness of complaints mechanisms.Compared with residents of larger towns, those of small communities were more likely to report they would complain to the local provider, whereas those in larger towns were more likely to mention Hospital Boards or the Commissioner. Deterrents to making complaints included the lack of services, scepticism about the role of complaints in bringing about change and an attitude that it was more appropriate to try to fix the problem than complain about it. Lack of awareness of appropriate complaint mechanisms which feed into quality assurance processes was also identified.Previously documented lower complaint rates from rural consumers can not be taken to mean greater satisfaction with health services.

Therapies for T2DM with RI are limited and may require dose adjustment. 52 wk, db, RCT examined efficacy/safety of QW Albi SQ (30 mg uptitrated to 50 mg if needed) vs. daily Sita in T2D pts and RI (eGFR ≥ 15 and < 90 mL/min/1.73 m2), A1C 7-10% on lifestyle (11% of pts) or Met, TZD, SU, or any combination (89% of pts).

Background/Purpose: While conducting pre-health assessments preadmission nurses discovered that some patients who take anticoagulant/antiplatelet medications do not understand how to manage these medications perioperatively. PURPOSE: Evaluation of whether or not same day surgical patients who take prescribed anticoagulant/antiplatelet medication and receive individualized education have increased knowledge on how to manage these medications perioperatively compared to patients who received standard care.

Objective: The goal of this project was to study the increasing risk of induction of labor in a community hospital and to determine whether it had an adverse effect on the rate of cesarean delivery. Study Design: From January 1, 1990, through July 31, 1997, 18,055 consecutive singleton pregnancies in women who were candidates for labor were reviewed via a comprehensive perinatal database. The risk of and indication for induction were reviewed. Cesarean delivery rates were calculated for nulliparous and multiparous patients by indication for induction and were compared with rates for patients who had spontaneous labor. Overall trends in cesarean delivery were reviewed for the duration of the study period. Results: The annual induction rate significantly rose from 32% to 43% at the conclusion of the study period. Labor was induced in nearly 40% of nulliparous patients. Postdate pregnancy was the most common indication for induction, although few patients were at or beyond 42 weeks' gestation. The cesarean delivery rate remained at or below 20% for the years of the study. No increase was noted in spite of the increasing risk of induction. However, for nulliparous patients who had elective induction of labor, the risk of cesarean delivery was twice that of nulliparous patients who had spontaneous labor. Conclusion: The use of induction methods has significantly increased in this community hospital. More than 40% of patients are now candidates for induction. The cesarean delivery rate remains low in this facility in spite of a marked increase in risk of operative delivery for nulliparous patients who undergo induction. (Am J Obstet Gynecol 1999;180:628-33.)

I’m sure I’m not the only one who is perturbed by evidence of a lack of caring in the NHS. As a doctor I know that this evidence is not just media scaremongering. I regularly treat acutely unwell elderly patients in need of hospitalisation who beg me not to send them in. I know sensible people who have given up going to their general practice, disillusioned by doctors who seem to be more interested in their computer than in them. I share the despair of patients with complex mental healthcare needs, refused help from psychiatric services because they have concomitant drug or alcohol issues or are labelled as “untreatable,” and the weary outrage of homeless people, discharged from hospital straight back onto the street while still recovering from a serious illness. I hear of growing numbers of Britons on the waiting list for assisted suicide in Zurich. All this makes me wonder whether we have given up on the notion of a caring health service. My personal disquiet about our system …

LCIS is a risk factor for the development of subsequent invasive breast carcinoma in either breast. Approximately 50 to 70% of these subsequent cancers are ILC. Not all LCIS progresses to invasive disease, and at present there are no biomarkers that predict which cases will develop ILC.

Background: Lobular carcinoma in situ (LCIS) is a risk factor for the development of subsequent invasive breast carcinoma in either breast. Approximately 50-70% of these subsequent cancers are invasive lobular carcinoma (ILC). Recent molecular evidence suggests that LCIS may be a precursor of ILC. However, not all LCIS progresses to invasive disease and at present there are no biomarkers that predict which cases are going to develop invasive disease. SNP-LOH analysis may be a useful method to analyse genome wide loss of heterozygosity (LOH) and copy number variation in LCIS and associated invasive disease in order to identify such biomarkers. The study of LCIS poses specific technical challenges as available samples are almost exclusively formalin fixed paraffin embedded (FFPE) tissue and LCIS tends to occur in small scattered foci which require micro-dissection.Aims: To assess the feasibility of performing SNP-LOH on micro-dissected FFPE tissue To compare patterns of LOH in pure LCIS and LCIS associated with ILCTo examine the genetic relationship between LCIS and associated ILCMethods: Tumour blocks were collected as part of the GLACIER Study (a study to investigate the Genetics of LobulAr Carcinoma In situ in EuRope). Tissue was micro-dissected from FFPE specimens. DNA was extracted with the DNEasy kit (Qiagen) if it was possible to micro-dissect by hand under a light microscope. For cases extracted using the laser capture microscope (LCM) the Picopure Kit (MDS Analytical Tech)) was used to extract DNA. SNP-LOH was performed using the GoldenGate Assay(Illumina) on 28 samples (20 LCIS, 8 ILC). A minimum of 250ng of DNA was required. For samples with low DNA yields, DNA was amplified using the Genomeplex Amplification Kit(Sigma).Results: Results were obtained on 24 samples that were micro-dissected under the light microscope and extracted using the DNEasy kit(Qiagen). Amplification of DNA was also possible from these samples and the SNP-LOH results for amplified DNA correlated with those for unamplified DNA(1 case).SNP-LOH was performed on 13 cases of classical LCIS: 6 pure LCIS, 7 with associated ILC. LOH events were more common in LCIS associated with invasive disease (range 2-5, median 3) than pure LCIS (range 0-5, median 2). The commonest change in both groups was 16q LOH (6/6 LCIS with invasive disease, 4/7 pure LCIS, p=0.12, Fishers Exact Test). 1q LOH was also present in all samples associated with invasive disease, but only identified in 3/7 samples of pure LCIS (p=0.049, Fishers Exact Test). There were also other regions of LOH that were more common in LCIS associated with ILC, but did not reach significance.Comparing LOH patterns in LCIS and associated ILC revealed that in 3/6 cases of ILC genetic changes were identical to those in the LCIS. In 2/6 cases the ILC had the same genetic changes but had also acquired new genetic changes. Interestingly in 1 case the LCIS had more genetic changes than the ILC.Conclusions: This pilot study has shown that it is possible to perform SNP-LOH on small amounts of micro-dissected FFPE tissue. The results confirm the findings of others that LCIS is a likely precursor lesion of ILC and suggest that even with this limited number of samples pure LCIS and LCIS associated with ILC may have different genetic profiles. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5169.

We welcome your recent focus on rural and remote health. Kamien and Cameron’s editorial addressed medical workforce supply issues,1 and the accompanying article ranged across not only workforce supply issues, but also broader systemic issues, including the roles of different levels of government.2 Coincidentally, the Australian Institute of Health and Welfare released its latest medical workforce report, which reported a rise in the number of doctors per head of population overall, particularly specialists, and particularly in urban areas, but decreased numbers of doctors in the bush, particularly in remote areas.3 Most of the media response ignored the contemporaneous nursing workforce report,4 which described a much more even geographical distribution of the nursing workforce — the largest health professional group.