Adherence to rivaroxaban for the treatment of venous thromboembolism-Results from the FIRST registry.

BACKGROUND: Medication nonadherence can result in poor clinical outcomes and significant costs to health care providers. When treating venous thromboembolism (VTE), subtherapeutic anticoagulation may contribute to complications such as recurrent VTE or postthrombotic syndrome. OBJECTIVES: To describe the extent, reasons for, and predictors of nonadherence to rivaroxaban for the treatment of VTE in clinical practice in the United Kingdom reported by participants of the FIRST registry. PATIENTS/METHODS: The FIRST registry was an observational, multicenter registry reporting on the use of rivaroxaban in routine clinical practice. FIRST registry participants completed an adherence screening questionnaire during their treatment and follow-up. RESULTS: In total, 1028 participants completed 1660 questionnaires over 2 years. One hundred thirteen of 1028 (11%) reported nonadherence at 28 days (interquartile range, 21-45). Reasons given for nonadherence at 1 month were forgetfulness (8.6% vs 74.7%; P < .001), carelessness (2.7% vs 27.3%; P < .001) or a change in routine (7.4% vs 25.5%; P < .001) reported by adherent and nonadherent participants, respectively. Older age (10-year increments) was the strongest predictor of good adherence (adjusted odds ratio, 1.21; 95% confidence interval, 1.06-1.39; 1 = adherent). CONCLUSIONS: Overall adherence to rivaroxaban was high, and most nonadherence was unintentional. Identification of those at risk of nonadherence may reduce the risk of VTE recurrence and long-term complications.

Rivaroxaban in acute venous thromboembolism: UK prescribing experience.

BACKGROUND: Rivaroxaban was reported as effective as traditional therapies for the acute treatment of venous thromboembolism (VTE) with fewer major bleeding complications in the seminal Einstein program and is now a recommended option for the treatment of VTE around the world. OBJECTIVE: To report the safety and efficacy of rivaroxaban in daily care for the management of acute VTE in the United Kingdom. PATIENTS/METHOD: The FIRST registry is a UK-only, multicenter, noninterventional, observational VTE study (NCT02248610). Consecutive patients diagnosed with acute VTE, managed with rivaroxaban, were recruited and followed for up to 5 years. The primary outcomes were treatment-emergent symptomatic objectively diagnosed recurrent VTE, major and clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. RESULTS: A total of 1262 participants were recruited between 2014 and 2018. Participants were heterogeneous, with age range 18 to 95 years, weight 35 to 234 kg, and maximum body mass index 64.4 kg/m2. The median duration of treatment exposure was 135 days (interquartile range [IQR], 84-307) and overall follow-up 497 days (IQR, 175-991). There were seven episodes of symptomatic VTE recurrence, 0.6%, (0.74/100 patient-years; 95% confidence interval [CI], 0.19-1.28). There were 79 of 1239 (6.4%), 8.66 of 100 patient-years (95% CI, 6.90-10.73) first episodes of major or CRNMB, which were most frequently reported by women aged <50 years as abnormal vaginal bleeding. CONCLUSIONS: Rivaroxaban is an effective and safe single drug modality for the treatment of VTE in daily practice in the United Kingdom. Data to determine the optimal anticoagulation therapy for women of childbearing age are needed.

The HAPI 'Hip Arthroscopy Pre-habilitation Intervention' study: does pre-habilitation affect outcomes in patients undergoing hip arthroscopy for femoro-acetabular impingement?

The purpose of this randomized prospective comparative controlled pilot study was to determine whether specific patient exercises done pre-hip arthroscopy surgery for femoro-acetabular impingement affected post-operative recovery. Between October 2013 and June 2014, 6 males and twelve females over the age of eighteen, who were listed for hip arthroscopy for femoro-acetabular impingement, were randomized into two groups. A hip-specific, 8-week home exercise programme was given to the experimental group before their surgery. The control group was given no instruction on exercise before surgery. All participants followed the same rehabilitation programme after surgery. Outcome measures were assessed at set time intervals. Hand held dynamometry was used to assess muscle strength, and the EQ-5D-5 L Score and the Non-Arthritic Hip Score were utilized. Sixteen participants completed the study (eight controls: mean age 41.75 years and eight intervention: mean age 37.5 years). A mixed ANCOVA analysis compared the treatment groups taking baseline values into account. A statistically significant difference was found between the treatment groups for knee extension strength on both operative (P = 0.05) and non-operative sides (P = 0.002), hip flexor strength operative side (P = 0.02) and for EQ-5D-5 L health (P = 0.03), in favour of the intervention group. There was no significant difference between the treatment groups for the other measures, although some tended towards significance. This small pilot study has been designed to aid the further research and the differences between the groups found in these results may inform future larger scale studies.

Predictors of birth-related post-traumatic stress symptoms: secondary analysis of a cohort study.

This study aimed to identify factors associated with birth-related post-traumatic stress symptoms during the early postnatal period. Secondary analysis was conducted using data from a prospective cohort study of 1824 women who gave birth in one large hospital in England. Post-traumatic stress symptoms were measured by the Impact of Event Scale at 6 to 8 weeks postpartum. Zero-inflated negative binomial regression models were developed for analyses. Results showed that post-traumatic stress symptoms were more frequently observed in black women and in women who had a higher pre-pregnancy BMI compared to those with a lower BMI. Women who have a history of mental illness as well as those who gave birth before arriving at the hospital, underwent an emergency caesarean section or experienced severe maternal morbidity or neonatal complications also showed symptoms. Women's perceived control during labour and birth significantly reduced the effects of some risk factors. A higher level of perceived social support during the postnatal period also reduced the risk of post-traumatic stress symptoms. From the perspective of clinical practice, improving women's sense of control during labour and birth appears to be important, as does providing social support following the birth.

Severe maternal morbidity and breastfeeding outcomes in the early post-natal period: a prospective cohort study from one English maternity unit.

Previous research has identified potential issues of establishing and maintaining breastfeeding among women who experience severe maternal morbidity associated with pregnancy and birth, but evidence in the UK maternity population was scarce. We explored the association between severe maternal morbidity and breastfeeding outcomes (uptake and prevalence of partial and exclusive breastfeeding) at 6 to 8 weeks post-partum in a UK sample. Data on breastfeeding outcomes were obtained from a large cohort study of women who gave birth in one maternity unit in England to assess the impact of women's experiences of severe maternal morbidity (defined as major obstetric haemorrhage, severe hypertensive disorder or high dependency unit/intensive care unit admission) on their post-natal health and other important outcomes including infant feeding. Results indicated that among women who responded (n = 1824, response rate = 53%), there were no statistically significant differences in breastfeeding outcomes between women who did or did not experience severe morbidity, except for women with severe hypertensive disorder who were less likely to breastfeed either partially or exclusively at 6 to 8 weeks post-partum. Rather, breastfeeding outcomes were related to multi-dimensional factors including sociodemographic (age, ethnicity, living arrangement), other pregnancy outcomes (neonatal intensive care unit admission, mode of birth, women's perceived control during birth) and post-natal psychological factors (depressive symptoms). Women who experience severe maternal morbidity can be reassured that establishing successful breastfeeding can be achieved. More studies are required to understand what support is best for women who have complex health/social needs to establish breastfeeding.

The relationship between severe maternal morbidity and psychological health symptoms at 6-8 weeks postpartum: a prospective cohort study in one English maternity unit.

BACKGROUND: The incidence of severe maternal morbidity is increasing in high-income countries. However, little has been known about the impact on postnatal morbidity, particularly on psychological health outcomes. The objective of this study was to assess the relationship between severe maternal morbidity (ie. major obstetric haemorrhage, severe hypertensive disorders or intensive care unit/obstetric high dependency unit admission) and postnatal psychological health symptoms, focusing on post-traumatic stress disorder (PTSD) symptoms at 6-8 weeks postpartum. METHOD: A prospective cohort study was undertaken of women who gave birth over six months in 2010 in an inner city maternity unit in England. Primary outcomes were prevalence of PTSD symptoms namely: 1) intrusion and 2) avoidance as measured using the Impact of Event Scale at 6 - 8 weeks postpartum via a self-administered postal questionnaire. Secondary outcomes included probable depression. Data on incidence of severe maternal morbidity were extracted from maternity records. Multivariable logistic regression analysis examined the relationship between severe maternal morbidity and PTSD symptoms taking into account factors that might influence the relationship. RESULTS: Of women eligible to participate (n=3509), 52% responded. Prevalence of a clinically significant level of intrusion and avoidance were 6.4% (n=114) and 8.4% (n=150) respectively. There was a higher risk of PTSD symptoms among women who experienced severe maternal morbidity compared with women who did not (adjusted OR = 2.11, 95%CI = 1.17-3.78 for intrusion; adjusted OR = 3.28, 95%CI = 2.01-5.36 for avoidance). Higher ratings of reported sense of control during labour/birth partially mediated the risk of PTSD symptoms. There were no statistically significant differences in the prevalence or severity of symptoms of depression. CONCLUSION: This is one of the largest studies to date of PTSD symptoms among women who had recently given birth. Findings showed that an experience of severe maternal morbidity was independently associated with symptoms of PTSD. Individually tailored care that increases women's sense of control during labour may be a protective factor with further work required to promote effective interventions to prevent these symptoms. Findings have important implications for women's health and the content and organisation of maternity services during and after the birth.

Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer.

PURPOSE: The Docetaxel Epirubicin Adjuvant (DEVA) trial evaluated the efficacy and toxicity of incorporating docetaxel after epirubicin to create a sequential anthracycline-taxane regimen in early breast cancer. PATIENTS AND METHODS: After complete tumor excision, postmenopausal women with node-positive early breast cancer were randomly assigned to either epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks for six cycles (EPI × 6) or three cycles of epirubicin 50 mg/m(2) on days 1 and 8 every 4 weeks followed by three cycles of docetaxel 100 mg/m(2) on day 1 every 3 weeks (EPI-DOC). A subset of patients also participated in a quality of life (QOL) study. The primary end point was disease-free survival (DFS). RESULTS: From 1997 to 2005, 803 patients entered DEVA (EPI × 6, n = 397; EPI-DOC, n = 406). At a median follow-up of 64.7 months (interquartile range, 45.2 to 84.4 months), 198 DFS events had been reported (EPI × 6, n = 114; EPI-DOC, n = 84). The 5-year DFS rates were 72.7% (95% CI, 68.0% to 77.3%) for epirubicin alone and 79.5% (95% CI, 75.2% to 83.8%) for epirubicin followed by docetaxel; evidence of improvement in DFS was observed with EPI-DOC (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.91; P = .008). One hundred twenty-seven patients have died (EPI × 6, n = 75; EPI-DOC, n = 52); a reduction in deaths was observed with EPI-DOC (HR, 0.66; 95% CI, 0.46 to 0.94; P = .02). The 5-year overall survival rates were 81.8% (95% CI, 77.7% to 85.9%) for epirubicin and 88.9% (95% CI, 85.5% to 92.2%) for epirubicin followed by docetaxel. Assessment of toxicity and QOL showed that EPI-DOC was associated with greater toxicity but with no difference in QOL between arms during follow-up. CONCLUSION: These results suggest, within a relatively small trial, that substitution of docetaxel for epirubicin for the last three cycles of chemotherapy results in improved outcome in postmenopausal women with node-positive, early breast cancer compared with six cycles of epirubicin monotherapy.

Tooth decay in alcohol abusers compared to alcohol and drug abusers.

Alcohol and drug abuse are detrimental to general and oral health. Though we know the effects of these harmful habits on oral mucosa, their independent and combined effect on the dental caries experience is unknown and worthy of investigation. We compared 363 "alcohol only" abusers to 300 "alcohol and drug" abusers to test the hypothesis that various components of their dental caries experience are significantly different due to plausible sociobiological explanations. After controlling for the potential confounders, we observe that the "alcohol and drug" group had a 38% higher risk of having decayed teeth compared to the "alcohol only" group (P < .05). As expected, those who belonged to a higher social class (OR = 1.98; 95% CI = 1.43-2.75) and drank wine (OR = 1.85; 95% CI = 1.16-2.96) had a higher risk of having more filled teeth. We conclude that the risk of tooth decay among "alcohol only" abusers is significantly lower compared to "alcohol and drug" abusers.

Pulse wave analysis in normal pregnancy: a prospective longitudinal study.

BACKGROUND: Outside pregnancy, arterial pulse wave analysis provides valuable information in hypertension and vascular disease. Studies in pregnancy using this technique show that vascular stiffness is raised in women with established pre-eclampsia. We aimed to establish normal ranges for parameters of pulse wave analysis in normal pregnancy and to compare different ethnic groups. METHODOLOGY/PRINCIPAL FINDINGS: This prospective study was conducted at The Homerton University Hospital, London between January 2006 and March 2007. Using applanation tonometry, the radial artery pulse waveform was recorded and the aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated. We recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia (n = 24, 3.6%) or gestational hypertension (n = 36, 5.4%) were excluded. We also excluded 47 women with other pregnancy complications or incomplete follow-up, leaving 541 healthy normotensive pregnant women for subsequent analysis. In the overall group of 541 women, there were no significant changes in AP or AIx-75 as pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell significantly from the first to the second trimester, then rose again in the third (P<0.001). The two main ethnic groups represented were Caucasian (n = 229) and Afrocaribbean (n = 216). There were no significant differences in AP or AIx-75 in any trimester between these two ethnic groups. CONCLUSIONS: This study is the largest to date of pulse wave analysis in normal pregnancy, the first to report on a subset of women studied longitudinally, and the first to investigate the effect of ethnicity. These data provide the foundation for further investigation into the potential role of this technique in vascular disorders in pregnancy.

The course of delirium in acute stroke.

BACKGROUND AND PURPOSE: several studies have assessed delirium post-stroke but conflicting results have been obtained. Also, the natural history and outcome of delirium post-stroke need to be fully elucidated. METHODOLOGY: eligible stroke patients were assessed for delirium on admission and for four consecutive weeks using the Confusion Assessment Method (CAM). Risk factors for delirium were recorded. Our outcome measures were length of stay, inpatient mortality and discharge destination. RESULTS: of 110 eligible patients, 82 were recruited over 7 months. Delirium was detected in 23 patients (28%); 21 of these were delirious on their first assessment. Sixty-nine per cent of patients who had four weekly assessments were delirious at 4 weeks. Multivariate logistic regression analysis was performed, and two models were identified. With unsafe swallow in the analysis, delirium was associated with an unsafe swallow on admission (OR 28.4, P<0.001), Barthel score < 10 (OR 32.1, P = 0.004) and poor vision pre-stroke (OR 110.8, P = 0.01). With unsafe swallow removed from the analysis, delirium was associated with an admission C-reactive protein (CRP) > 5 mg/l (OR 10.2, P = 0.009), Barthel score < 10 (OR 46.5, P = 0.001) and poor vision pre-stroke (OR 85.2, P = 0.01). Delirious patients had a higher mortality (30.4% vs. 1.7%, P<0.001), longer length of stay (62.2 vs. 28.9 days, P<0.001) and increased risk of institutionalisation (43.7 vs. 5.2%, OR 14, P<0.001). CONCLUSIONS: delirium is common post-stroke. Most cases develop at stroke onset and remain delirious for an appreciable period. Delirium onset is associated with stroke severity (low admission Barthel), unsafe swallow on admission, poor vision pre-stroke and a raised admission CRP. Delirium is a marker of poor prognosis.

The evaluation of delirium post-stroke.

OBJECTIVE: The aim of this study was to assess and compare the Confusion Assessment Method (CAM) and the Delirium Rating Scale (DRS) in the detection of delirium in the acute stroke setting, when used by a non-psychiatrist doctor. METHODS: Consecutive participants within 4 days of an acute stroke were screened for delirium using the CAM and the DRS. Patients also had a Mini-Mental State Examination at each assessment. Patients were screened weekly for a maximum of 4 weeks. The CAM and DRS were compared against each other with respect to agreement and applicability. RESULTS: Of 110 eligible patients, 82 were recruited over a 7 month period. Delirium developed in 23 patients (28%), 21 of whom developed delirium during week 1. We found high agreement between the CAM and the DRS in the detection of stroke in the acute stroke setting (kappa values 0.97, 0.86, 0.79 and 1 at weeks 1, 2, 3 and 4, respectively). In addition, there was strong correlation between low MMSE scores (MMSE less that 10) and delirium (kappa scores 1.0, 0.82, 0.83 and 1.0 at weeks 1, 2, 3 and 4, respectively). CONCLUSIONS: Delirium is a common complication post-stroke. The CAM is equivalent to the DRS in the acute stroke setting when used by a trained non-psychiatrist. A low MMSE score may have a small benefit in identifying patients that are at risk of having delirium.

Development and validation of a patient-based disease activity score in rheumatoid arthritis that can be used in clinical trials and routine practice.

OBJECTIVE: Assessor-based disease activity measures such as the Disease Activity Score in 28 joints (DAS28), although widely used in rheumatoid arthritis (RA), have high interobserver variability. We developed and validated a patient-based disease activity score (PDAS) as an alternative assessment. METHODS: Patients' assessments of swollen or tender joints, visual analog scales for pain and general health, the Health Assessment Questionnaire, and erythrocyte sedimentation rate (ESR) were used to develop the PDAS. In a developmental cohort (204 patients), regression analyses determined the best fit with the DAS28. A validation cohort (322 patients) subsequently evaluated criterion and construct validity against a range of outcome measures, including the Nottingham Health Profile (NHP) and Short Form 36 (SF-36). Sensitivity to change was assessed in 56 patients after 6 months of treatment with disease-modifying antirheumatic drugs or biologics. RESULTS: In the developmental cohort, the PDAS with ESR (PDAS1) and without ESR (PDAS2) achieved excellent fit with the DAS28 (r = 0.88 and 0.74, respectively). In the validation cohort, the PDAS showed high criterion validity by correlation with the DAS28 (PDAS1: r = 0.89, PDAS2: r = 0.76). Construct validity was demonstrated by high correlations with a range of disease activity measures (r > or = 0.45), whereas low correlations (r < 0.45) with mental and social components of the SF-36 and NHP indicated divergent validity. The PDAS and DAS28 had similar sensitivity to change, determined using effect sizes (DAS28 = 1.03, PDAS1 = 1.02, PDAS2 = 0.77) or standardized response means (DAS28 = 0.79, PDAS1 = 0.77, PDAS2 = 0.73). CONCLUSION: The PDAS1 and PDAS2 are valid and sensitive tools to assess disease activity in RA. They appear suitable for clinical decision making, epidemiologic research, and clinical trials.

The reporting quality of randomised controlled trials in surgery: a systematic review.

OBJECTIVES: In order to examine the reporting quality of urological RCTs, the initial objectives of this study were to evaluate the degree to which RCTs involving urological surgical techniques (as the intervention) published in the years 2000-2003 complied with the CONSORT statement, and to assess trends and patterns of compliance. Following our initial findings in urology, we extended the methodology to a number of other specialties to assess whether our findings in urology could be generalised to other surgical disciplines. METHODS: The Royal Society of Medicine (RSM) Library was commissioned to search the Medline and Cochrane databases for RCTs in compliance with the study inclusion criteria below. Additional analyses of five other specialties (non-urological trials: cardiovascular, gastrointestinal, hepatic, orthopaedic and vascular) were also made. For the non-urological trials, 15 English language trials (from each specialty) were randomly picked from a blast search conducted by the RSM for the year 2003. The RCTs were given a score out of 22, reflecting how many of the 22 CONSORT items were complied with (with each item being given equal weighting), this score was termed the "CONSORT score". RESULTS: Urology trials: In total 122 RCT abstracts were identified which met the inclusion criteria for this study. From these, 32 were excluded as they were follow-up studies, involved a virtual procedure or were a cost analysis, leaving 90 RCTs published across 35 different journals which were analysed (68.2%, 90/122). The average score of 11.1 for urological trials indicates that RCTs in our sample do not comply with the CONSORT statement. No trials reported how they implemented their randomisation process. Only 46% of RCTs stated that they had permission from an ethics review board, 20% had declared their sources of funding, 14% stated whether there were any conflicts of interest and only 1.1% stated their trial registry number. For non-urological studies, an average CONSORT score of 11.2 was obtained. CONCLUSION: Clinical research teams conducting RCTs in urology and other surgical disciplines demonstrate poor compliance with the CONSORT statement. We would recommend that trials should be registered at their outset and that urological and other surgical journals to consider supporting the CONSORT statement and to have compliance 'hard-wired' into their submission, editorial and peer-review processes. Since it seems the best researchers are unable to produce an RCT results which enable surgical techniques to be critically assessed, there is a need for education about the CONSORT statement and its importance at all levels of surgical training. We believe that an open debate is needed on the possible role of other research designs, such as tracker studies. Whether this study actually raises the question of how appropriate RCTs are to surgical techniques, we leave to the reader.

Personality differences between doctors and their patients: implications for the teaching of communication skills.

OBJECTIVE: To establish, as part of a wider study into specialty choice and job satisfaction, whether the personality profiles of a sample of doctors differed from those of the UK population at large, i.e. their potential patients, and the implications this might have for the doctor/patient consultation process. DESIGN: The Myers-Briggs Type Indicator (MBTI), which measures normal personality differences, was administered by post to five cohorts of doctors (n = 464) who had qualified from a London medical school during the 1980s. SETTING: United Kingdom. PARTICIPANTS: 313 (67.5%) of the medical graduates. MAIN OUTCOME MEASURES: Personality profiles of the respondents compared to those of the UK adult population norms, a proxy for their potential patients. RESULTS: The doctors in this sample differed significantly from the UK adult population norms on most of the dimensions of personality measured, including those which measure an individual's preferred mode of perception, i.e. how one likes to take in information and learn about things. This suggests potential points for miscommunication in the doctor/patient consultation process. CONCLUSIONS: This research should be replicated to see if the results are generalizable. Nevertheless, the findings do indicate that these doctors might benefit from education in the concept of psychological type differences and how these could affect communication with their patients. Training in how to "flex" their consultation style, when necessary, to take into account possible personality differences between themselves and their patients could enhance the outcome of the interaction for both parties.