A Multicentre Study of Thromboprophylaxis in Pregnancy.

Venous thromboembolism (VTE) is a leading cause of maternal mortality. The risk increases with increasing maternal age, mode of delivery and medical co-morbidities. Thromboprophylaxis with low molecular weight heparin (LMWH) has been shown to be both safe and efficacious. The aim of this study was to prospectively investigate the incidence of maternal risk factors in pregnant women admitted to hospital, to calculate their VTE risk status and to investigate if they were receiving appropriate thromboprophylaxis. All patients admitted to the participating hospitals on the day of investigation were assessed for risk of VTE on the basis of hospital chart review. Five Hundred and forty women were recruited from 16 hospitals. Almost 32% (31.7%) were receiving thromboprophylaxis with LMWH. Just under 80% of patients were on the correct thromboprophylaxis strategy as defined by the RCOG guideline but 49% were under-dosed. The odds of receiving appropriate thromboprophylaxis were significantly increased if the woman was >35 years 0or with parity>3.

Venous Thromboembolism - Risk Assessment Tool and Thromboprophylaxis Policy: A National Survey.

Venous Thromboembolic (VTE) events in hospitalised patients are associated with significant mortality and morbidity and a major economic burden on the health service. It is well established in the literature that active implementation of a mandatory risk assessment tool and thromboprophylaxis policy reduces the incidence of hospital associated thrombosis (HAT). This study examines the utilization of a VTE risk assessment tool and thromboprophylaxis (TP) policy in Irish hospitals that manage acute admissions. A national survey was distributed to forty acute hospitals throughout Ireland. The response rate was 78% (31/40). The results showed that only 26% (n=8/31) of acute hospitals in Ireland have a local implemented TP policy. Six (75%) of these eight had a risk assessment tool in conjunction with the TP policy. All respondents who did not report to have a TP policy and risk assessment tool agreed that they should implement VTE prevention policy at their hospital. Based on the data from this survey and evidence from the effectiveness of the VTE prevention programme introduced in the United Kingdom, there is a need for a national risk assessment and thromboprophylaxis policy in Ireland. This change in practice would have the potential to prevent or reduce the morbidity and mortality associated with hospital acquired thrombosis.

Incidence of Hospital Acquired Thrombosis (HAT) in a Tertiary Care Hospital.

Venous thromboembolism (VTE) is a major cause of preventable morbidity and mortality in hospitalized patients. In spite of guidelines, VTE prophylaxis continues to be underutilised, and hospital acquired thrombosis (HAT) continues to be a problem. This study was conducted to estimate the incidence of HAT in a tertiary referral centre and to examine whether VTE risk assessment and thromboprophylaxis (TP) were implemented. Patients 18 years and above, with a radiologically-confirmed acute VTE during the study period of 15 weeks were included. Acute VTE was diagnosed in 100 patients and HAT was diagnosed in 48. There were 12,024 admissions over the study period, therefore the incidence of HAT was 0.4%. TP was prescribed in only 35% of patients, and 65% did not receive any or appropriate TP. Hospitals without active implementation of a formal risk assessment tool and TP policy are likely to continue to have increased incidence of HAT.

Hospital Acquired Thrombosis (HAT) Prevention in an Acute Hospital; A Single Centre Cross-Sectional Study.

Evidence based guidelines are effective in reducing incidence of venous thromboembolism (VTE) which is associated with morbidly, mortality and economic burden. This study aimed to identify the proportion of inpatients who had a VTE risk assessment (RA) performed and who received thromboprophylaxis (TP), in Cork University Hospital. There was no structured RA tool at the time; information was obtained from medical and drug charts to ascertain if a RA was performed. Patients were then RA by researchers and stratified as per NICE guidelines and the proportion who received TP was calculated. One thousand and nineteen inpatients were screened. Risk was documented in 24% of cases. TP was prescribed in 43.2% of inpatients. Following application of a RA tool >80% were at high risk of VTE with low risk of bleeding with TP prescription in 46.3% of inpatients. A national collaborative effort should be encouraged to develop a standardized approach for safe RA of inpatients and prescription of TP for prevention of HAT.

Vitamin D, vitamin A, the primary melanoma transcriptome and survival.

Survival from melanoma is influenced by several, well-established clinical and histopathological factors, e.g. age, Breslow thickness and microscopic ulceration. We (the Section of Epidemiology and Biostatistics, University of Leeds) have carried out research to better understand the biological basis for these observations. Preliminary results indicated a protective role for vitamin D in melanoma relapse and that higher vitamin D was associated with thinner primary melanomas. Funding from the British Skin Foundation enabled JNB to establish a study of the effects of vitamin A in melanoma. The results suggested that vitamin A could reduce the protective effect of vitamin D in terms of overall survival. Therefore, we propose that vitamin D3 supplementation alone might be preferable to combined multivitamin preparations, where vitamin D supplementation is deemed to be appropriate. Proving a causal link between vitamin D and melanoma-specific survival is challenging. We have shown limited evidence of causation in a Mendelian randomization experiment (described in more detail later). Recent work in Leeds has also shown that higher vitamin D may be protective for microscopic ulceration. Taken together, vitamin D appears to be associated with less aggressive primary melanomas and may itself influence outcome. We continue to explore the role of vitamin D in melanoma survival and the optimum levels that might be crucial.

A Cost Minimisation Analysis of NOACs Compared to Warfarin to Attain Therapeutic Anticoagulation amongst AF Patients, Pre- and Post- Cardioversion.

Atrial fibrillation can be managed with anticoagulation and restoration of normal sinus rhythm using direct current cardioversion (DCCV). To reduce the risk of thromboembolism, anticoagulation pre-and-post DCCV is recommended. This study investigates the cost effectiveness of using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients pre-and-post DCCV. Propensity score matching revealed no statistically significant difference in outcomes from using NOACs and Warfarin. A cost minimisation study was performed; demonstrating a cost differential of €209 between those administered NOACs and warfarin pre- and post-DCCV. This study demonstrates how using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients pre-and-post DCCV is cost effective.

Nanoscale Trapping and Squeeze-Out of Confined Alkane Monolayers.

We present combined force curve and conduction atomic force microscopy (AFM) data for the linear alkanes CnH2n+2 (n = 10, 12, 14, 16) confined between a gold-coated AFM tip and a graphite surface. Solvation layering is observed in the force curves for all liquids, and conduction AFM is used to study in detail the removal of the confined (mono)layer closest to the graphite surface. The squeeze-out behavior of the monolayer can be very different depending upon the temperature. Below the monolayer melting transition temperatures the molecules are in an ordered state on the graphite surface, and fast and complete removal of the confined molecules is observed. However, above the melting transition temperature the molecules are in a disordered state, and even at large applied pressure a few liquid molecules are trapped within the tip-sample contact zone. These findings are similar to a previous study for branched alkanes [ Gosvami Phys. Rev. Lett. 2008, 100, 076101 ], but the observation for the linear alkane homologue series demonstrates clearly the dependence of the squeeze-out and trapping on the state of the confined material.

Economic evaluation of a randomized controlled trial of pharmacist-supervized patient self-testing of warfarin therapy.

WHAT IS KNOWN AND OBJECTIVE: The increase in numbers of patients requiring oral anti-coagulation testing in outpatient clinics has focused attention on alternative flexible systems of anti-coagulation management. One option is pharmacist led patient self-testing (PST) of international normalised ratio (INR) levels. PST has demonstrated improvements in anti-coagulation control, but its cost-effectiveness is inconclusive. This study reports the first cost-effectiveness evaluation of a randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on oral anti-coagulation therapy. METHODS: We conducted an economic evaluation alongside a randomised controlled trial investigating a pharmacist led PST method. The primary outcome was to determine the cost effectiveness of PST in comparison with usual care (management in a hospital based anti-coagulation clinic). Long term anti-coagulation patients were recruited to a 6 month cross over study between PST and routine care in an anti-coagulation clinic. Economic evaluation was from the healthcare payer perspective. RESULTS AND DISCUSSION: On a per patient basis over a 6 month period, PST resulted in an incremental cost of €59.08 in comparison with routine care. Patients achieved a significantly higher time in therapeutic range (TTR) during the PST arm in comparison with routine care, (72 ± 19.7% vs. 59 ± 13.5%). Overall cost of managing a patient through pharmacist supervised PST for a 6 month period is €226.45. Additional analysis of strategies from a societal perspective indicated that PST was the dominant strategy. WHAT IS NEW AND CONCLUSION: Pharmacist led patient self-testing is a viable method of management. It provides significant increases in anti-coagulation control for a minimal increase in cost.

Thromboprophylaxis in myeloma: what is happening outside of clinical trials?

Patients with myeloma are at high risk of venous thromboembolism (VTE). There is no consensus about what agent to use or what haematologists are doing in clinical practice. A survey was sent to haematologists treating patients with myeloma in Ireland. 32/45 (71%) responded. 13/28 (46%) felt that VTE affected < 5% of patients. However, 8/28 (29%) felt it affected 10-19%. Thromboprophylaxis was most commonly used in patients on lenalidomide; 25/28 (89%) and thalidomide; 23/28 (82%). 23/28 (82%) used LMWH and 20/28 (71%) used aspirin either very frequently or frequently. 3/28 (11%) had used dabigatran/rivaroxaban despite there being little evidence to support their use. Efficacy was the most important factor in choosing an agent for 25/28 (89%). Bleeding was not felt to be an issue 15/29 (52%) were not using thromboprophylaxis guidelines. This survey demonstrated wide variation in the beliefs and practices regarding the burden of VTE in patients with myeloma and the need for thromboprophylaxis.

Diagnosing HIV infection in patients presenting with glandular fever-like illness in primary care: are we missing primary HIV infection?

OBJECTIVES: The aim of the study was to examine the prevalence of HIV infection in patients presenting in primary care with glandular fever (GF)-like illness. METHODS: Samples from primary care submitted for a GF screen between April 2009 and June 2010 were identified. Samples without an HIV request were anonymized and retrospectively tested using a 4th-generation HIV antigen/antibody screening test. Reactive samples were further confirmed by an HIV antibody only test, with or without a p24 antigen assay. Antibody avidity testing based on the Recent HIV Infection Testing Algorithm (RITA) was used to identify individuals with evidence of recent acquisition (within 4-5 months). RESULTS: Of 1046 GF screening requests, concomitant HIV requests were made in 119 patients. Excluding one known positive patient, 2.5% (three of 118) tested HIV positive. Forty-five (4.3%) had a subsequent HIV test through another consultation within 1 year; of these, 4.4% (two of 45) tested positive. Of the remaining 882 patients, 694 (78.7%) had samples available for unlinked anonymous HIV testing, of which six (0.9%) tested positive. The overall HIV prevalence was 1.3% (11 of 857), with 72.7% (eight of 11) of cases missed at initial primary care presentation. Four of the nine (44.4%) available positive samples had evidence of recent acquisition, with three (75.0%) missed at initial primary care presentation. CONCLUSION: Low levels of HIV testing in patients presenting in primary care with GF-like illness are resulting in a significant number of missed HIV and seroconversion diagnoses. Local policy should consider adopting an opt-out strategy to include HIV testing routinely within the GF-screening investigation panel.

Implementation of thromboprophylaxis guidelines.

Venous thromboembolism (VTE) remains one of the leading direct causes of maternal death. Risk factors for VTE and prophylaxis guidelines have been highlighted by the Royal College of Obstetricians and Gynaecologists (RCOG). A cross sectional study was completed in Cork University Maternity Hospital (CUMH) to determine pattern of VTE risk and compliance with 2004 RCOG guidelines. 364 women's charts were reviewed. Forty percent (n = 145) were at risk for VTE, 69% (n = 100) of these received thromboprophylaxis but only 54% (n = 54) received the correct weight adjusted dose. Three of four morbidly obese women in this study received recommended thromboprophylaxis but none at the appropriate dose. Only 67% (n = 245) had a recorded body mass index (BMI). Increased BMI is a significant risk factor for VTE and should be measured and recorded at the booking visit. Awareness of the risks for VTE and the need for appropriate dosing should be improved.

Conventional versus ultra-low dose computed tomogram in Crohn's disease: Do morphomics correlate with clinical data?

BACKGROUND: Cross-sectional study to assess the body composition of patients with Crohn's disease (CD) on standard (SDCT) and low dose CT (LDCT) protocols for the abdomen and pelvis (CTAP). We aimed to assess if a low dose CT protocol reconstructed with model-based iterative reconstruction (IR) could evaluate body morphometric data comparable to standard dose examination. METHODS: The CTAP images of 49 patients who underwent a low dose CT scan (20% of standard dose) and a second at standard dose minus 20% were assessed retrospectively. Images were collected from the PACS system, deidentified and analysed using a web-based semi-automated threshold-based segmentation tool (CoreSlicer), capable of identifying tissue type based on differences in attenuation co-efficient. The cross-sectional area (CSA) and Hounsfield units (HU) of each tissue was recorded. RESULTS: Muscle and fat CSA is well preserved on comparing these derived metrics from low dose and standard dose CT scans of abdomen and pelvic in CD ((LDCT:SDCT mean CSA (cm2); Psoas muscle - 29.00:28.67, total lumbar muscle - 127.45:125.55, visceral fat- 110.44:114.16, subcutaneous fat - 250.88:255.05)). A fixed difference exists when assessing the attenuation of muscle, with higher attenuation on the low dose protocol (LDCT:SDCT mean attenuation (HU); Psoas muscle - 61.67:52.25, total lumbar muscle - 49.29:41.20). CONCLUSION: We found comparable CSA across all tissues (muscle and fat) on both protocols with a strong positive correlation. A marginally lower muscle attenuation suggestive of less dense muscle was highlighted on SDCT. This study augments previous studies suggesting that comparable and reliable morphomic data may be generated from low dose and standard dose CT images. IMPLICATIONS FOR PRACTICE: Threshold-based segmental tools can be used to quantify body morphomics on standard and low dose computed tomogram protocols.

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland.

BACKGROUND: There are limited data on the use of ustekinumab outside of clinical trials. OBJECTIVES: To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. METHODS: A retrospective case-note review of 129 patients with psoriasis treated with ustekinumab. RESULTS: Baseline Psoriasis Area and Severity Index (PASI) was 22·9±10·1 (mean±SD). After 16weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n=80/127) of patients, although four patients required concomitant therapy at the 16-week time point. Previous biologic use did show a small, non-significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n=5/17) of individuals weighing 90-100kg and treated with the standard 45mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups <80, 80-90, 100-110 and >110kg, respectively (P=0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n=3/129) of patients. CONCLUSIONS: Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short-term therapeutic efficacy with an acceptable short-term safety profile.

Complete skin examination is essential in the assessment of dermatology patients: findings from 483 patients.

BACKGROUND: Dermatological teaching has traditionally stressed that complete skin examination is essential in the assessment of patients with potential skin disease. OBJECTIVES: To determine whether complete skin examination results in increased diagnoses of skin malignancies that would not have been discovered otherwise. METHODS: New patients (n = 483) attending a dermatology clinic in a university teaching hospital and private dermatology practice had a complete skin examination, as is our normal practice. These patients were seen over a 9-month period (January-September 2009). All patients were examined by the same consultant dermatologist. Data were collected on patients' sex, age, presenting complaint and findings on complete skin examination. RESULTS: Two nodular malignant melanomas with mean Breslow thickness of 0·6 mm (0·4%) and one melanoma in situ were identified at sites distant from the patient's presenting complaint. Sixteen patients (3·3%) had a basal cell carcinoma that would not have been discovered if the presenting lesion alone had been examined. Thirty-three patients (6·8%) had actinic keratoses or squamous cell carcinoma in situ and nine (1·9%) had dysplastic naevi. A further 21 patients (4·3%) had a suspicious lesion biopsied or excised with subsequent benign histology. Seventy-three patients (15·1%) had other benign dermatological diagnoses requiring treatment or investigation. CONCLUSIONS: In a 9-month period, in a sample of 483 new patients, three patients (0·6%) had potentially lethal skin malignancies identified that would not have been diagnosed without a complete skin examination. Sixteen (3·3%) patients had basal cell carcinomas that would have been missed without complete skin examination. This study confirms the traditional teaching that complete skin examination has the potential to reduce morbidity and mortality from cutaneous malignancy.

Alcohol misuse in patients with psoriasis: identification and relationship to disease severity and psychological distress.

BACKGROUND: Moderate to severe psoriasis is associated with increased alcohol intake and excessive mortality from alcohol-related causes. Alcohol biomarkers provide an objective measure of alcohol consumption. Carbohydrate-deficient transferrin (CDT) is the single most sensitive and specific alcohol biomarker. OBJECTIVES: To assess alcohol consumption in a cohort of patients with moderate to severe psoriasis using standard alcohol screening questionnaires and biomarkers. We investigated whether there was an association between alcohol intake, anxiety, depression and disease severity. METHODS: Consecutive patients with chronic plaque psoriasis were recruited and completed a range of anonymized assessments. Psoriasis severity, anxiety and depression, and the impact of psoriasis on quality of life were assessed. Alcohol screening questionnaires were administered. Blood specimens were taken and γ-glutamyltransferase (γGT) and CDT were measured. RESULTS: A total of 135 patients completed the study. Using validated questionnaires, between 22% and 32% had difficulties with alcohol. Seven per cent had CDT > 1·6% indicating a heavy alcohol intake. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire was superior to other validated questionnaires in detecting alcohol misuse. There were no significant associations between measures of excessive alcohol consumption and disease severity. Excessive alcohol intake as measured by the CAGE questionnaire was associated with increased depression (P = 0·001) but other measures of alcohol excess did not correlate with psychological distress. Men had significantly more difficulties with alcohol than women (P < 0·001). CONCLUSION: Alcohol misuse is common in patients with moderate to severe psoriasis. Screening with the AUDIT questionnaire and CDT may allow the identification of patients who are misusing alcohol and allow appropriate intervention.

Complications following pancreatic transplantations: imaging features.

Whole organ vascularized pancreatic transplant is a recognized treatment for diabetes and is increasingly being performed worldwide. The procedure itself is complex and is associated with significant mortality and morbidity. Despite improvements in surgical techniques, postoperative complications of pancreatic transplantation are still common and include graft rejection, pancreatitis, peripancreatic fluid collections, exocrine leaks, vascular thrombosis, and hemorrhage. In this pictorial essay, we review clinical presentation and imaging features of these complications. We also briefly discuss technique and complications of islet cell transplants.

Clinical utility of genotypic resistance tests for HIV-1-infected patients with low-level virological failure.

The usefulness of genotypic resistance tests (GRT) among HIV-1 patients with low-level virological failure (LLVF) was evaluated. Up to 78% of samples with <1,000 copies/ml were sequenced successfully. For samples with 50 to 200 copies/ml, the success rate was as high as 69%. LLVF should not deter clinicians from requesting GRT.

Temperature dependence of solvation forces as measured in atomic force microscopy.

An atomic force microscope (AFM) has been used to study the effect of temperature on solvation forces in the liquids octamethylcyclotetrasiloxane, n-hexadecane, and n-dodecanol confined between the AFM tip and a graphite surface. Discrete solvation layers can be observed for all three liquids at all the temperatures measured (298-348K). However, with increasing temperature there is a significant decrease in the magnitude of the measured solvation forces and a reduction in the number of solvation oscillations which can be observed. Solvation forces per se are only weakly temperature dependent and the most plausible explanation is that we are measuring how the layers are squeezed from the tip-sample gap. The squeeze out process is a thermally activated phenomenon and gives rise to the large change in the magnitude of the force oscillations with temperature. A simple analysis is provided based on transition rate theory. The large change in solvation force with temperature has implications for the measurement of localized forces using AFM, particularly in interpreting biological interactions and single asperity friction.

Utilization of HIV point-of-care testing clinics in general practice and genitourinary medicine services in south-east London.

We compared the utilization of HIV point-of-care testing (POCT) clinics in a general practice and a genitourinary (GU) medicine service. Retrospective case-note review of patients attending the general practice HIV POCT clinic from February 2005 to July 2007 was undertaken. Those attending the GU medicine service over the same period were used as a comparator group. HIV POCT clinics in general practice when compared with GU medicine services were significantly more likely to be utilized by those of Black ethnicity (Black African 61/370 [16.5%] vs. 107/1231 [8.7%], P < 0.001; Black Caribbean 19/370 [5.1%] vs. 11/1231 [0.9%], P < 0.001 and Black Other 20/370 [5.4%] vs. 26/1231 [2.1%], P = 0.001, respectively). Fewer men who have sex with men attended for HIV POCT in general practice than in GU medicine; 82/238 (34.5%) vs. 337/816 (41.3%), P = 0.058. We have demonstrated that HIV POCT clinics in primary care and GU medicine attract different 'at-risk' groups and provide increased opportunity for testing.