The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity.

A missense variant (c.1637C>T, T546M) in ABCC11 encoding the MRP8 (multidrug resistance protein 8), a transporter of 5-fluorodeoxyuridine monophosphate, has been associated with an increased risk of 5-fluorouracil-related severe leukopenia. To validate this association, we investigated the impact of the ABCC11 variants c.1637C>T, c.538G>A and c.395+1087C>T on the risk of early-onset fluoropyrimidine-related toxicity in 514 cancer patients. The ABCC11 variant c.1637C>T was strongly associated with severe leukopenia in patients carrying risk variants in DPYD, encoding the key fluoropyrimidine-metabolizing enzyme dihydropyrimidine dehydrogenase (odds ratio (OR): 71.0; 95% confidence interval (CI): 2.5-2004.8; Pc.1637C>T*DPYD=0.013). In contrast, in patients without DPYD risk variants, no association with leukopenia (OR: 0.95; 95% CI: 0.34-2.6) or overall fluoropyrimidine-related toxicity (OR: 1.02; 95% CI: 0.5-2.1) was observed. Our study thus suggests that c.1637C>T affects fluoropyrimidine toxicity to leukocytes particularly in patients with high drug exposure, for example, because of reduced fluoropyrimidine catabolism.

Palliative Care Quality Indicators for Patients with End-Stage Liver Disease Due to Cirrhosis.

BACKGROUND AND AIMS: There are guidelines for the medical management of cirrhosis and associated quality indicators (QIs), but QIs focusing on standards for palliative aspects of care are needed. METHODS: We convened a 9-member, multidisciplinary expert panel and used RAND/UCLA modified Delphi methods to develop palliative care quality indicators for patients with cirrhosis. Experts were provided with a report based on a systematic review of the literature that contained evidence concerning the proposed candidate QIs. Panelists rated QIs prior to a planned meeting using a standard 9-point RAND appropriateness scale. These ratings guided discussion during a day-long phone conference meeting, and final ratings were then provided by panel members. Final QI scores were computed and QIs with a final median score of greater than or equal to 7, and no disagreement was included in the final set. RESULTS: Among 28 candidate QIs, the panel rated 19 as valid measures of quality care. These 19 quality indicators cover care related to information and care planning (13) and supportive care (6). CONCLUSIONS: These QIs are evidence-based process measures of care that may be useful to improve the quality of palliative care. Research is needed to better understand the quality of palliative care provided to patients with cirrhosis.

[What is new in 2014 for the specialist in hospital internal medicine? The point of view of university hospital chief residents]. / L'année 2014 mise en perspective par les internistes hospitaliers.

The year 2014 was rich in significant advances in all areas of internal medicine. Many of them have an impact on our daily practice and on the way we manage one problem or another. From the use of the ultrasound for the diagnosis of pneumonia to the choice of the site of venous access and the type of line, and the increasing complexity of choosing an oral anticoagulant agent, this selection offers to the readers a brief overview of the major advances. The chief residents in the Service of internal medicine of the Lausanne University hospital are pleased to share their readings.

Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Do I have enough time? The impact of recruiting patients to a randomised controlled trial at recruiting centres.

INTRODUCTION: This paper explores the impact of recruiting patients to a randomised controlled trial (RCT) at recruiting centres. This large multicentre RCT examining the efficacy of chewing gum compared to ibuprofen in the relief of orthodontic pain was carried out across nine recruiting centres. METHOD: The work diaries of clinicians and supporting staff at recruiting centres were analysed over a four-month period from September to December 2011. This quantified the amount of clinical and non-clinical time spent on research duties. RESULTS: Over this time period 98 patients were recruited across seven trial sites. On average, patient recruitment had a direct clinical impact of 19 minutes per patient recruited. The time commitment on trial administration outside the clinical sessions was much higher, averaging at 110 minutes per patient recruited, giving the overall time spent on the trial 129 minutes per patient. CONCLUSIONS: This information will be valuable to lead researchers when calculating the full economic cost of a proposed clinical trial and therefore when applying for grant funding. It may also be valuable to clinicians and their managers when considering becoming a principle investigator (PI) in a RCT. Although the impact on clinical time was 19 minutes per patient recruited, there is a considerably higher (almost six times greater) time commitment in administration around the recruitment of patients.

Assessment and management of patients with cognitive impairment and dementia in primary care.

OBJECTIVES: To evaluate care provided by primary care physicians in community practice to older patients presenting with cognitive impairment and dementia. DESIGN: Secondary analysis of an intervention study. SETTING: Primary care clinics. PARTICIPANTS: 101 patients 75 years and older enrolled in the ACOVE-2 study who presented with a new cognitive problem, new dementia, or prevalent dementia. MEASUREMENTS: Patients assessment and management were evaluated from medical record review and caregiver interviews. RESULTS: Among 34 patients presenting with a new cognitive problem, half received a cognitive assessment comprising of a test of memory and one other cognitive task, 41% were screened for depression and 29% were referred to a consultant. Of the 27 patients with newly diagnosed dementia, 15% received the components of a basic neurological examination, one-fifth received basic laboratory testing and for one third the medical record reflected an attempt to classify the type of dementia. Counseling was under-reported in the medical record compared to the caregiver interview for the 101 patients with dementia, but even the interview revealed that about half or fewer patients received counseling about safety and accident prevention, caregiver support or managing conflicts. Less than 10% were referred to a social worker. CONCLUSION: This small but detailed evaluation suggests patients presenting with cognitive problems to primary care physicians do not consistently receive basic diagnosis and management.

Disfunción eréctil: un marcador de disfunción endotelial: estudio de casos y control / Higher frequency of erectile dysfunction among patients hospitalized for an acute coronary syndrome

Background: Endothelial dysfunction is associated to erectile dysfunction. This last condition can even be considered as a cardiovascular risk factor. Aim: To determine the frequency of erectile dysfunction among hospitalized patients with and without acute coronary syndromes. Material and Methods: Prospective cross sectional study in which all male patients, aged 40 to 70 years admitted to the emergency room or medicine service of a general hospital in a period of two months, were included. Those with acute coronary syndromes were considered as cases and those without, as controls. The international erectile dysfunction index questionnaire (IIEF-5) was applied to all. Results: Forty four patients with acute coronary syndrome aged 57 +/- 8 years and 46 controls aged 56 +/- 9 years were included. Erectile dysfunction was present in 34 (77 percent) cases and 20 (44 percent) controls (p < 0.01). The odds ratio of having erectile dysfunction among coronary patients was 4.4 (95 percent confidence intervals 1.6-12.3). Conclusions: There was a higher frequency of erectile dysfunction among patients with acute coronary syndromes.

17-year follow-up of the rough-blasted threaded Weill cup in uncemented total hip arthroplasty.

INTRODUCTION: For uncemented hip arthroplasty, various cup designs are available. The threaded Weill acetabular component (Weill cup; Zimmer, Winterthur, Switzerland) has been used for more than 20 years, with poor results of the smooth threaded design. Our study was intended to assess the 17-year outcome of the rough-blasted option of the threaded Weill cup. MATERIALS AND METHODS: Between 1987 and 1988, a series of 86 rough-blasted threaded Weill cups were implanted in combination with the CLS Spotorno stem (Zimmer Ltd, Germany) The patients' mean age at the time of surgery was 50 years (range 19-67 years). 67 out of 86 hips (78%) were available for a follow-up at a mean of 17 years (range 16-18 years). Radiographs were available from 55 out of 63 unrevised hips (87%) and analyzed for radiolucency and PE wear. RESULTS: Two out of 86 cups (3%) were revised due to aseptic loosening and another two cups (3%) were awaiting revision for the same reason. Ten patients (10 cups, 12%) were lost to follow-up, and nine patients with nine cups (11%) had deceased without radiographic signs of cup failure. Cup survival with "revision or awaiting revision" as endpoint was 86% (95% CI 75-92%). No deep infections occurred, and no polyethylene insert was exchanged. The Harris hip score was excellent in 37 out of 67 clinically examined hips (55%), good in 18 hips (26%), satisfactory in 5 hips (8%) and moderate or poor in 5 hips (8%) and 2 hips (3%), respectively. CONCLUSION: The rough-blasted threaded Weill cup provides a good long-term performance in cementless total hip arthroplasty. The results compare favourably to the smooth threaded cup design.

Use of statin therapy to reduce cardiovascular risk in older patients.

Background. Cardiovascular disease is the principal cause of mortality in older individuals, and more than 80% of deaths due to coronary heart disease or stroke occur in patients over 65 years of age. Hyperlipidemia is one of the main modifiable risk factors for cardiovascular disease. Current guidelines recommend the use of statins to reduce low-density lipoprotein cholesterol to appropriate targets based on an individual's cardiovascular risk, and clearly state that older age should not be a barrier to treatment. Despite extensive evidence demonstrating clear benefit with statin therapy in older individuals, this population remains chronically undertreated. Scope. This paper provides an overview of the current evidence available regarding the efficacy and safety of statin therapy to reduce cardiovascular risk in older patients. We use hypothetical case studies to address some of the questions frequently posed by physicians responsible for the cardiovascular health of older patients. Conclusions. Various factors may account for the failure to provide appropriate treatment, including a lack of awareness of clinical benefits and perceived safety issues. However, if current guidelines are followed and older patients treated to appropriate LDL-C goals, the likelihood of cardiovascular events will be reduced in this high-risk population. Employing an evidence-based approach to the management of cardiovascular risk in older patients is likely to yield benefits in terms of overall cardiovascular burden.

3D surface imaging in dentistry - what we are looking at.

3D imaging has been widely used within various fields of dentistry to aid diagnosis, in treatment planning and appliance construction. Whereas traditionally this has involved the use of impression materials together with plaster or stone models, modern techniques are continually evolving which use virtual 3D images. These electronic virtual images are created using either contact or non-contact optical scanning techniques, but there are limitations, the most important of which is that any new virtual surface image is created from a series of discrete data points. It is not created from a continuous stream of data relating to the original object. This means that computer software has to be used to recreate a possible best fit, virtual surface from the data obtained. This paper describes the principles behind 3D scanning technology, the limitations of 3D imaging as well as current and possible uses of such imaging in clinical dentistry.

A randomized control clinical trial investigating orthodontic bond failure rates when using Orthosolo universal bond enhancer compared to a conventional bonding primer.

OBJECTIVE: This study assessed the in vivo bond failure rates of orthodontic brackets bonded using Orthosolo universal bond enhancer and compared it with the conventional bonding primer, Transbond XT. DESIGN: This was a single centre randomized controlled clinical study. SETTING: Department of Child Dental Health, Bristol Dental Hospital, Bristol, UK. MATERIALS AND METHODS: Thirty-three consecutive patients undergoing fixed orthodontic appliance therapy were included in this study. Using a split-mouth design, diagonally opposite quadrants were randomly allocated a primer, either Orthosolo universal bond enhancer (Ormco, Orange, CA, USA) or Transbond XT primer (3M Unitek, Monrovia, CA, USA). A total of 555 teeth were bonded using a conventional acid-etch technique. 277 received Orthosolo as their primer and 278 received the Transbond XT primer. Bond failures and their positions were recorded at six months. RESULTS: There was an overall bond failure rate of 1.26%. Four brackets failed in the Orthosolo group (0.72%) and three failed in the Transbond XT group (0.54%). CONCLUSION: There was no clinical or statistically significant difference in the in vivo bond failure rates between orthodontic brackets bonded using either Orthosolo universal bond enhancer or the conventional Transbond XT primer.

Beneficial effects of aggressive low-density lipoprotein cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study.

OBJECTIVE: To examine by secondary analysis of the Treating to New Targets (TNT) study whether the benefits of intensive versus standard levels of lipid lowering are equally applicable to women. METHODS: A total of 10 001 patients (1902 women) with stable coronary heart disease (CHD) were randomised to double-blind treatment with atorvastatin 10 or 80 mg/day for a median follow-up of 4.9 years. RESULTS: In women and men, intensive treatment with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events compared with atorvastatin 10 mg. Among women, the relative and absolute reductions were 27% and 2.7%, respectively (hazard ratio (HR) = 0.73, 95% confidence interval (CI) 0.54 to 1.00, p = 0.049). In men, the corresponding rate reductions were 21% and 2.2% (HR = 0.79, 95% CI 0.69 to 0.91, p = 0.001). The number needed to treat value (to prevent one cardiovascular event over 4.9 years compared with patients treated with atorvastatin 10 mg) for atorvastatin 80 mg was 29 for women and 30 for men. Rates of death of non-cardiovascular origin in the atorvastatin 80 mg and atorvastatin 10 mg were 3.6% and 1.6%, respectively (p = 0.004) among women, and 2.8% and 3.1% (p = 0.47) among men. CONCLUSION: Intensive lipid-lowering treatment with atorvastatin 80 mg produced significant reductions in relative risk for major cardiovascular events compared with atorvastatin 10 mg in both women and men with stable CHD.

Coronary heart disease in women: update 2008.

Coronary heart disease (CHD) remains the leading cause of mortality for US women, responsible for almost 250,000 deaths annually. Preventive heart-health behavioral changes by women and aggressive coronary risk reduction can decrease the number of women disabled and killed by CHD. Angina is the predominant initial and subsequent presentation of CHD in women; categorization of chest pain and risk stratification of women assume pivotal roles. A robust evidence-based algorithm can guide cardiovascular imaging techniques to evaluate women with suspected myocardial ischemia to detect those with worsened survival. Restricted functional capacity (<5 METs) is a consistent marker of worsened prognosis. Younger women have substantially higher mortality rates than men following myocardial infarction and coronary bypass surgery. Although these women have more comorbidity and risk factors, other issues including biological differences, treatment differences, and psychosocial factors require management strategies tailored to the unique needs of women.

Coronary heart disease in women: battle is won, but the war remains.

According to the most recent report of the US National Heart, Lung, and Blood Institute, mortality from coronary heart disease has declined in women from one in three to one in four. Due to massive campaigning efforts in educating the medical community and the general public, coronary heart disease has become increasingly recognized as a woman's disease. Indeed, it is the number one killer in women, exceeding cancer and infectious diseases. Numerous observational studies, clinical trials, and reports have indicated that there are gender-specific differences in the presentation, diagnosis, treatment, and outcomes of coronary heart disease. One common theme, not only in United States, but world-wide is the underutilization of known and validated medical and interventional therapies in women compared to men. Even though previously conducted large, randomized controlled trials had limited numbers of women, recent large scale cardiac trials in women have enabled the development of evidence-based guidelines for coronary heart disease diagnosis and management in women. Importantly, menopausal hormone therapy and antioxidant vitamin therapy do not protect post-menopausal women from coronary heart disease. Aggressive life-style and pharmacologic management of known coronary risk factors in women should be a top priority to improve coronary heart disease morbidity and mortality. Research data continue to emerge to fill the gaps of how gender affects atherosclerosis; in the meantime, continued patient and physician education to increase awareness of coronary heart disease may help to eliminate some of the gender-based disparities in the delivery of coronary care to women.

Peri-operative second molar tube failure during orthognathic surgery: two case reports.

With improvements in bonding techniques, bracket base design and bond strengths, molar tubes are becoming more popular in orthodontics. Molar tubes make an attractive alternative to conventional banding due to a reduction in clinical bonding time and ease of placement on partially erupted teeth. The use of molar tubes negates the need for orthodontic separation and subsequent cementation of bands, and offers improved periodontal health. Their use on terminal molars, however, should be limited to non-orthognathic cases. This paper presents two cases of peri-operative second molar tube failure during orthognathic surgery. They are presented in the hope that it will highlight the importance of banding the distal terminal molar in orthognathic cases to prevent loss of molar tubes and peri-operative contamination of the surgical wound site.

Direct digital lateral cephalometry: the effects of JPEG compression on image quality.

OBJECTIVES: This study used an aluminium test object to assess the effect of the Joint Photographics Expert Group (JPEG) compression algorithm, on direct digital cephalometric image quality. METHODS: The aluminium block of 15 steps, with 20 holes in each step was radiographed in a Planmeca Proline 2002 digital cephalometric machine with Dimaxis2 software. Six different JPEG compression ratios were used to capture the cephalometric images. These ratios were 60%, 70%, 80%, 90%, TOP QUALITY JPEG (TQJPEG 98%) and TIFF (uncompressed). The images were taken at 68 kV and 12 mA with a 7 s exposure. Six experienced observers viewed the monitor displayed images, which were presented randomly. This was repeated one month later. The number of holes detected by each observer was plotted against each compression ratio. Intra-observer and inter-observer reproducibility was calculated using the Mann-Whitney U-test. Differences between the compression ratios were assessed using a Kruskal-Wallis one-way analysis of variance. RESULTS: When comparing intra-observer reproducibility, it was found that there were only four of 36 comparisons that showed a statistically significant difference (Observer 1: 60% (P=0.004), TQJPEG (P=0.019); Observer 2: TIFF (P=0.005); Observer 3: 90% (P=0.007)). Statistically, there was no significant difference with inter-observer reproducibility. There was no statistically significant difference between the image quality obtained from each compression ratio. CONCLUSIONS: The results showed that JPEG compression does not have any effect on the perceptibility of landmarks in the aluminium test object used in this study.

Religiousness and spirituality among HIV-infected Americans.

PURPOSE: To describe the demographic and clinical factors associated with the importance of religiousness and spirituality among patients with human immunodeficiency virus (HIV) infection in the United States. METHODS: Longitudinal study of a nationally representative cohort of 2266 patients receiving care for HIV infection surveyed in 1996 and again in 1998. Measures included 12 items assessing religious affiliation and attendance, the importance of religion and spirituality in life, and religious and spiritual practices. Multi-item religiousness and spirituality scales were constructed. RESULTS: Eighty percent of respondents reported a religious affiliation. Sixty-five percent affirmed that religion and 85% that spirituality was "somewhat" or "very" important in their lives. A majority indicated that they "sometimes" or "often" rely on religious or spiritual means when making decisions (72%) or confronting problems (65%). Women, nonwhites, and older patients were more religious and spiritual. Residents of regions other than the western United States reported higher religiousness. High school graduates were more religious and spiritual than those with less education. Patients who did not report one of the risk factors assessed for HIV infection had higher religiousness scores than injection drug users (IDUs). Women, nonwhites other than Hispanics, patients older than 45 years of age compared to those between 18 and 34 years of age, and more educated patients reported higher spirituality. Clinical stage was not associated with religiousness or spirituality. CONCLUSIONS: A large majority of HIV-infected patients in the United States affirm the importance of religiousness and spirituality. These findings support a comprehensive, humanistic approach to the care of HIV-infected patients.

Women in cardiology: the US experience.

"You are not required to complete the work, but neither are you at liberty to abstain from it.."-Rabbi Tarfon, Pirke Avot 2:16.

Developing quality indicators for older adults: transfer from the USA to the UK is feasible.

BACKGROUND: Measurement of the quality of health care is essential for quality improvement, and patients are an underused source of data about quality of care. We describe the adaptation of a set of USA quality indicators for use in patient interview surveys in England, to measure the extent to which older patients receive a broad range of effective health care interventions in both primary and secondary care. METHOD: One hundred and nineteen quality indicators covering 16 clinical areas, based on a set of indicators for the care of vulnerable elderly patients in the USA, were reviewed by a panel of 10 clinical experts in England. A modified version of the RAND/UCLA appropriateness method was used and panel members were supplied with literature reviews summarising the evidence base for each quality indicator. The indicators were sent for comment before the panel meeting to UK charitable organisations for older people. RESULTS: The panel rated 102 of the 119 indicators (86%) as valid for use in England; 17 (14%) were rejected as invalid. All 58 indicators about treatment or continuity and follow up were rated as valid compared with just over half (13 of 24) of the indicators about screening. CONCLUSIONS: These 102 indicators are suitable for use in patient interview surveys, including the English Longitudinal Study of Ageing (ELSA). The systematic measurement of quality of care at the population level and identification of gaps in quality is essential for quality improvement. There is potential for transfer of quality indicators between countries, at least for the health care of older people.