Religious Values in Clinical Practice are Here to Stay.

Research to date has shown that health professionals often practice according to personal values, including values based on faith, and that these values impact medicine in multiple ways. While some influence of personal values are inevitable, awareness of values is important so as to sustain beneficial practice without conflicting with the values of the patient. Detecting when own personal values, whether based on a theistic or atheistic worldview, are at work, is a daily challenge in clinical practice. Simultaneously ethical guidelines of tone-setting medical associations like American Medical Association, the British General Medical Council and Australian Medical Association have been updated to encompass physicians' right to practice medicine in accord with deeply held beliefs. Framed by this context, we discuss the concept of value-neutrality and value-based medical practice of physicians from both a cultural and ethical perspective, and reach the conclusion that the concept of a completely value-neutral physician, free from influence of personal values and filtering out value-laden information when talking to patients, is simply an unrealistic ideal in light of existing evidence. Still we have no reason to suspect that personal values, whether religious, spiritual, atheistic or agnostic, should hinder physicians from delivering professional and patient-centered care.

Predictive values of colorectal cancer alarm symptoms in the general population: a nationwide cohort study.

BACKGROUND: Alarm symptoms are used in many cancer referral guidelines. The objectives were to determine the 1-year predictive values (PVs) of colorectal cancer (CRC) alarm symptoms in the general population and to describe the proportion of alarm symptoms reported prior to diagnosis. METHODS: A nationwide prospective cohort of 69,060 individuals ≥40 years randomly selected from the Danish population was invited to complete a survey regarding symptoms and healthcare-seeking in 2012. Information on CRC diagnoses in a 12-month follow-up came from the Danish Cancer Registry. PVs and positive and negative likelihood ratios were calculated. RESULTS: A total of 37,455 individuals participated (response rate 54.2%). Sixty-four individuals were diagnosed with CRC. The single symptom with the highest positive PVs (PPV) and LR+ was rectal bleeding. PPVs were generally higher among individuals aged ≥75 years and highest among those reporting at least one specific alarm symptom that led to a GP contact. CONCLUSION: In general, the PPVs of CRC alarm symptoms are low and the NPVs high, especially in the youngest age groups. The LR + show a relative association with specific symptoms like rectal bleeding. Future campaigns on early diagnosis of CRC should focus on healthcare-seeking when experiencing rectal bleeding and target older people with the highest incidence.

A Plain Language Summary of "Dostarlimab for primary advanced or recurrent endometrial cancer".

What is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that uses a patient's own immune system to treat endometrial cancer. Dostarlimab is a type of medicine called an immunotherapy. Immunotherapies help the immune system find and attack cancer cells. Dostarlimab stops cancer cells from being able to hide from the immune system, which allows the patient to have a boosted immune response against their cancer.The RUBY study is a phase 3 clinical study of primary advanced (cancer that has spread outside the uterus) or recurrent (cancer that has come back) endometrial cancer. A phase 3 clinical study looks at how well a new treatment works compared to the standard, or usual, treatment in a large patient population. The RUBY study is testing how well dostarlimab given with chemotherapy, followed by dostarlimab alone, works at delaying primary advanced or recurrent endometrial cancer from getting worse and preventing patients from dying, compared to chemotherapy given alone (the current standard treatment for primary advanced or recurrent endometrial cancer).What were the results? When dostarlimab was given with chemotherapy, this combination was found to delay primary advanced or recurrent endometrial cancer from getting worse and to prevent patients from dying, compared with chemotherapy given alone (without dostarlimab). Patients in the study who received dostarlimab with chemotherapy had a 36% lower risk of dying or having their cancer get worse.What do the results mean? The results from this study contributed to the approval of dostarlimab with chemotherapy as a new treatment option for patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer. As of the publication of this plain language summary of publication (PLSP), this combination of dostarlimab with chemotherapy has been approved in the United States of America, the United Kingdom, the European Union and Hong Kong.Clinical Trial Registration: NCT03981796 (RUBY).

Second victims in the labor ward: Are Danish midwives and obstetricians getting the support they need?

OBJECTIVE: To describe midwives' and obstetricians' experiences on the level of support from colleagues and managers in Danish labor wards following adverse events. DESIGN, SETTING AND PARTICIPANTS: A 2012 National survey of Danish obstetricians and midwives was conducted to assess the level of support received in the workplace. MAIN OUTCOME MEASURES: Scales on social community at work, social support from colleagues and immediate superiors, and use of support mechanisms on labor wards after serious adverse events were assessed. RESULTS: 2098 midwives and obstetricians were invited to complete the survey (response rate 59%), and the analyses were carried out on the 593 respondents who had been involved in at least one traumatic childbirth at their current place of work. Respondents experienced high levels of social support from colleagues and social community at work, midwives significantly higher than obstetricians, and 95% of respondents had talked to colleagues about an adverse event. Respondents generally experienced low levels of social support and feedback from immediate superiors, and only 49% had talked to their immediate superior about an adverse event. Fifty% believed that the hospital had a clear process through which they could report adverse events, and 44% knew how to access the necessary confidential emotional support at work. CONCLUSIONS: Midwives and obstetricians experienced high levels of social support and feedback from colleagues who are the most frequent individuals to consult after adverse events. We strongly suggest developing second victim support programmes with a focus on offering peer support from qualified and trained peers.

Predictive values of upper gastrointestinal cancer alarm symptoms in the general population: a nationwide cohort study.

BACKGROUND: Survival rates for upper gastrointestinal (GI) cancer are poor since many are diagnosed at advanced stages. Fast track endoscopy has been introduced to prompt diagnosis for patients with alarm symptoms that could be indicative of upper GI cancer. However, these symptoms may represent benign conditions and little is known about the predictive values of alarm symptoms of upper GI cancer in the general population. METHODS: The study is a nationwide cohort study of 60,562 individuals aged 45 years or above randomly selected from the Danish general population. Participants were invited to complete a survey comprising of questions on several symptom experiences, including alarm symptoms for upper GI cancer within the past four weeks. The participants were asked about specific symptoms (repeated vomiting, difficulty swallowing, signs of upper GI bleeding or persistent and recent-onset abdominal pain) and non-specific symptoms (nausea, weight loss, loss of appetite, feeling unwell and tiredness). We obtained information on upper GI cancer diagnosed in a 12-month period after completing the questionnaire from the Danish Cancer Registry. We calculated positive predictive values and positive likelihood ratios for the association between alarm symptom and subsequent upper GI cancer. RESULTS: A total of 33,040 individuals above 45 years completed the questionnaire, yielding a response rate of 54.6%. Respondents were fairly respresentative of the study sample. During the follow-up period, 18 people were diagnosed with upper GI cancer. The number of incident cancers was similar among eligible non-respondents. Two thirds of the respondents with an upper GI malignancy had experienced one or more alarm symptoms. The positive predictive value for being diagnosed with upper GI cancer after reporting a least one alarm symptom was 0.1% (95% CI:0.0-0.1%). The positive likelihood ratio was 4.4 for specific alarm symptoms and 1.1 for non-specific alarm symptoms. CONCLUSIONS: We found that positive predictive values of alarm symptoms of upper GI cancer experienced in the general population are low. It is important knowledge that despite denoted alarm symptoms even patients with specific alarm symptoms of upper GI cancer have a low risk of being diagnosed with upper GI cancer.

Correction to: Impact of socioeconomic position and distance on mental health care utilization: a nationwide Danish follow-up study.

In the original publication of this article, Table 3 was published incorrectly. The corrected table is shown below.

Impact of socioeconomic position and distance on mental health care utilization: a nationwide Danish follow-up study.

PURPOSE: To determine the impact of socioeconomic position (SEP) and distance to provider on outpatient mental health care utilization among incident users of antidepressants. METHOD: A nationwide register-based cohort study of 50,374 person-years. RESULTS: Persons in low SEP were more likely to have outpatient psychiatrist contacts [odds ratio (OR) 1.25; confidence interval (CI) 1.17-1.34], but less likely to consult a co-payed psychologist (OR 0.49; CI 0.46-0.53) and to get mental health service from a GP (MHS-GP) (OR 0.81; CI 0.77-0.86) compared to persons in high SEP after adjusting for socio-demographics, comorbidity and car ownership. Furthermore, persons in low SEP who had contact to any of these therapists tended to have lower rates of visits compared to those in high SEP. When distance to services increased by 5 km, the rate of visits to outpatient psychiatrist tended to decrease by 5% in the lowest income group (IRR 0.95; CI 0.94-0.95) and 1% in the highest (IRR 0.99; CI 0.99-1.00). Likewise, contact to psychologists decreased by 11% in the lowest income group (IRR 0.89; CI 0.85-0.94), whereas rate of visits did not interact. CONCLUSION: Patients in low SEP have relatively lower utilization of mental health services even when services are free at delivery; co-payment and distance to provider aggravate the disparities in utilization between patients in high SEP and patients in low SEP.

Early intervention for childhood overweight: A randomized trial in general practice.

OBJECTIVE: To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice. DESIGN: Prospective randomized controlled trial. SETTING: A total of 60 general practices in the former County of Funen, Denmark. SUBJECTS: Overweight children, identified by International Obesity Task Force criteria, aged 5-9 years. INTERVENTION: Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations. MAIN OUTCOME MEASURES: Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time. RESULTS: A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI -0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.09) in Model 2, respectively, was detected. The majority of the participants (2/3) continued in the study for more than one year in both models, with a mean of 12 consultations in general practice. CONCLUSION: In this particular setting the two intervention strategies against overweight and obesity did not differ significantly with regard to change in BMI z-scores.

Primary non-adherence in general practice: a Danish register study.

PURPOSE: The aim of this study was to describe primary non-adherence (PNA) in a Danish general practitioner (GP) setting, i.e. the extent to which patients fail to fill the first prescription for a new drug. We also assessed the length of time between the issuing of a prescription by the GP and the dispensing of the drug by the pharmacist. Lastly, we sought to identify associations between PNA and the characteristics of the patient, the drug and the GP. METHODS: By linking data on issued prescriptions compiled in the Danish General Practice Database with data on redeemed prescriptions contained in the Danish National Prescription Registry, we calculated the rate of PNA among Danish patients from January 2011 through to August 2012. Characteristics associated with PNA were analysed using a mixed effects logistic regression model. RESULTS: A total of 146,959 unique patients were started on 307,678 new treatments during the study period. The overall rate of PNA was 9.3 %, but it varied according to the major groups of the Anatomical Therapeutic Chemical (ATC) Classification System, ranging from 16.9 % for "Blood and bloodforming organs" (ATC group B) to 4.7 % for "Cardiovascular system" (ATC group C). Most of the patients redeemed their prescriptions within the first week. Older age, high income and a diagnosis of chronic obstructive pulmonary disease were found to be significantly associated with lower rates of PNA, while polypharmacy and a diagnosis of ischaemic heart disease were associated with higher rates of PNA. CONCLUSIONS: The overall rate of PNA among Danish residents in a GP setting was 9.3 %. Certain drug classes and patient characteristics were associated with PNA.

Measures of 'exposure needed for one additional patient to be harmed' in population-based case-control studies.

PURPOSE: The magnitude of risk for adverse drug reactions may be communicated by a measure of 'exposure needed for one additional patient to be harmed' (ENH). We present four ENH measures, based on four different counterfactual contrasts, as illustrated by the known effects of NSAID use on peptic ulcer bleeding. METHODS: The four measures were basic ENH (estimating the excess risk when treating the entire source population versus treating no one), age-restricted ENH (the entire source population above, e.g. 50 years old treated versus no one above 50 years old treated), standardised ENH (a population of similar age and gender distribution as those actually treated versus same subjects not treated) and naturalistic ENH (those actually treated versus same subjects not treated). Data were derived from a case-control dataset on NSAIDs and severe peptic ulcer bleeding, collected in Funen County in 1995-2006. We incorporated prescription and census data to account for the source population's drug use. RESULTS: Estimates of basic, age-restricted, standardised and naturalistic ENH were 619 person-years (py) (95% confidence interval (CI): 558-684), 223 py (CI: 201-246), 131 py (CI: 118-144) and 162 py (CI: 151-173). The age-restricted ENH showed strong dependence on the chosen age limit. CONCLUSION: The differing counterfactual contrasts underlying the ENH result in widely different estimates. These differences reflect the clinical and epidemiological aspects of NSAID-related peptic ulcer bleeding. The ultimate choice of ENH measure will depend on epidemiological or clinical considerations and on availability of data.

Influence of comorbidity on cancer patients' rehabilitation needs, participation in rehabilitation activities and unmet needs: a population-based cohort study.

PURPOSE: This study aims to investigate possible associations between cancer survivors' comorbidity status and their (1) need for rehabilitation, (2) participation in rehabilitation activities and (3) unmet needs for rehabilitation in a 14-month period following date of diagnosis. METHODS: We performed a population-based cohort study including incident cancer patients diagnosed from 1 October 2007 to 30 September 2008 in two regions in Denmark. Fourteen months after diagnosis, participants completed a questionnaire measuring different aspects and dimensions of rehabilitation. Individual information on comorbidity was based on hospital contacts from 1994 and until diagnosis, subsequently classified according to the Charlson comorbidity index. Logistic regression analyses were used to explore the association between comorbidity and outcomes for rehabilitation. Analyses were conducted overall and stratified for gender, age and cancer type. RESULTS: A total of 3,439 patients responded (70%). Comorbidity at all levels was statistically significant associated with a physical rehabilitation need, and moderate to severe comorbidity was statistically significant associated with a need in the emotional, family-oriented and financial areas as well as participation in physical-related rehabilitation activities. Stratified analyses showed that significant results in most cases were related to being older than 65 years or having colorectal or prostate cancer. CONCLUSIONS: Comorbidity at all levels was significantly associated with needs for physical rehabilitation. Moderate to severe comorbidity was further associated with other areas of need and participation in physical area activities. This should be taken into account when planning rehabilitation interventions for cancer survivors. Differences among subgroups could help target interventions and should be explored further.

Long-term treatment with probiotics in primary care patients with irritable bowel syndrome--a randomised, double-blind, placebo controlled trial.

OBJECTIVE. Meta-analyses have indicated effect of probiotics on irritable bowel syndrome (IBS). However, few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting. We aimed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up. MATERIAL AND METHODS. We randomized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 10(10) CFU per capsule. Primary endpoint was proportion of responders defined as patients reporting adequate relief (AR) at least 50% of the time in the 6-month treatment period. Secondary outcomes were proportions of patients reporting AR at different time points, and change in gastrointestinal symptoms and health-related quality of life (HrQOL) from baseline to 6 and 12 months. RESULTS. A total of 131 patients were included in this study. The proportion of responders in the treatment period was 52% (35/67) in the probiotic group versus 41% (26/64) in the placebo group, p = 0.18. Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment. Patients improved in HrQOL, but with no statistically significant difference between the groups. CONCLUSION. During a 6-month treatment period, we were not able to detect a positive effect of probiotic when compared with placebo.

Unmet needs in cancer rehabilitation during the early cancer trajectory--a nationwide patient survey.

BACKGROUND: A cancer diagnosis may lead to psychosocial problems and physical symptoms that can be relieved during rehabilitation. The aim of this study was to analyse patient-perceived unmet needs of rehabilitation close to time of diagnosis, i.e. frequencies of unmet needs and the association with sociodemographic characteristics, cancer type and treatment. MATERIAL AND METHODS: All adult residents of Denmark diagnosed with cancer for the first time from 1 May to 31 August 2010 were mailed a patient questionnaire two to five months following diagnosis. The study population was identified by use of national administrative registers. Data on rehabilitation, family situation, education, and cancer treatment were obtained from the questionnaire, while sex, birth year and cancer type were obtained from the Danish National Patient Registry. The association between each type of unmet needs and the variables sex, age, cancer diagnosis, treatment, education, cohabitation status, and children (living at home and away from home) was analysed using multiple logistic regression. RESULTS: Among the 4346 participants (64.7%) unmet needs were reported with regard to talking to patients in the same situation (24.1%), counselling with a psychologist (21.4%), physical rehabilitation (18.8%), practical help (17.3%), and counselling related to work or education (14.8%). Differences were observed with regard to type of unmet needs, sociodemographic and clinical characteristics, but generally, young age, male sex, low educational level and living alone increased the adjusted odds ratios of unmet needs. Breast cancer and to some extent melanoma cancer decreased the odds. CONCLUSION: Unmet needs of rehabilitation are frequent during the early cancer trajectory and sociodemographic and clinical inequalities exist. The results support guideline recommendations of integration of cancer rehabilitation from the beginning of the cancer trajectory. Early interventions tailored to men, patients with low educational level, living alone, or treated with chemotherapy may help counterbalancing social and clinical inequalities in the long run.

Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation: a register-based nested case-control study.

OBJECTIVES: The objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation. DESIGN: The study was designed as a case-control study, nested within users of VKA and with tramadol use as our main exposure. We used conditional logistic regression to control for potential confounders. SETTING: Prescription data from primary care were obtained from Odense Pharmacoepidemiological Database (OPED). Information about hospital admissions was obtained from the patient administrative system of Funen County (FPAS). SUBJECTS: Both cases and controls were selected from users of VKA. Cases were defined by being hospitalised with a main diagnosis indicating excessive anticoagulation. For each case, we selected 15 controls among VKA users, matched by age and sex. MAIN OUTCOME MEASURE: Odds ratio for experiencing excessive anticoagulation attributable to the use of tramadol. RESULTS: A total of 178 patients were included, 30 of which were exposed to tramadol, along with 2643 controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for experiencing excessive anticoagulation during use of tramadol was 3.1 (1.9-5.2). This corresponds to, on average, one excess case per 250 treatment years (CI 125-584). The result is potentially confounded by concomitant paracetamol use and the presence of acute illness. CONCLUSION: Caution is advised when using tramadol in patients using VKA, and if possible, an alternative pain-medication should be used.

Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease: a population-based cohort study.

BACKGROUND: Socioeconomic status is known to influence the prevalence, severity and mortality of obstructive lung diseases, but it is uncertain whether it affects the use of diagnostic spirometry in patients initiating treatment for these conditions. The objective of this paper was to examine a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. METHODS: We conducted a population-based cohort study. Danish national registers were linked, retrieving data on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. RESULTS: A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years of age, being unemployed was significantly associated with reduced odds of having spirometry performed, the strongest association was seen in men (OR = 0.82, CI = 0.73-0.91). Medium income was associated with increased odds of having spirometry performed in men (OR =1.18, CI = 1.06-1.30) and high educational level (>12 years) was associated with reduced odds of having spirometry performed in women (OR = 0.86, CI = 0.78-0.94). Cohabitation status was not associated with having spirometry performed. Among medication users over 65 years of age, living alone was associated with reduced odds of having spirometry performed among men (OR = 0.78, CI = 0.69-0.88). CONCLUSION: Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed and among women with higher education is required when initiating medication.

Process-related factors associated with disciplinary board decisions.

BACKGROUND: In most health care systems disciplinary boards have been organised in order to process patients' complaints about health professionals. Although, the safe-guarding of the legal rights of the involved parties is a crucial concern, there is limited knowledge about what role the complaint process plays with regard to board decision outcomes. Using complaint cases towards general practitioners, the aim of this study was to identify what process factors are statistically associated with disciplinary actions as seen from the party of the complainant and the defendant general practitioner, respectively. METHODS: Danish Patient Complaints Board decisions concerning general practitioners completed in 2007 were examined. Information on process factors was extracted from the case files and included complaint delay, complainant's lawyer involvement, the number of general practitioners involved, event duration, expert witness involvement, case management duration and decision outcome (discipline or no discipline). Multiple logistic regression analyses were performed on compound case decisions eventually involving more general practitioners (as seen from the complainant's side) and on separated decisions (as seen from the defendant general practitioner's side). RESULTS: From the general practitioner's side, when the number of general practitioners involved in a complaint case increased, odds of being disciplined significantly decreased (OR=0.661 per additional general practitioner involved, p<0.001). Contrarily, from the complainant's side, no association could be detected between complaining against a plurality of general practitioners and the odds of at least one general practitioner being disciplined. From both sides, longer case management duration was associated with higher odds of discipline (OR=1.038 per additional month, p=0.010). No association could be demonstrated with regard to complaint delay, lawyer involvement, event duration, or expert witness involvement. There was lawyer involvement in 5% of cases and expert witness involvement in 92% of cases. The mean complaint delay was 3 months and 18 days and the mean case management duration was 14 months and 7 days. CONCLUSIONS: Certain complaint process factors might be statistically associated with decision outcomes. However, the impact diverges as seen from the different parties. Future studies are merited in order to uncover the judicial mechanisms lying behind.

General practice variation in spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease in Denmark: a population-based observational study.

BACKGROUND: Spirometry testing is essential to confirm an obstructive lung disease, but studies have reported that a large proportion of patients diagnosed with COPD or asthma have no history of spirometry testing. Also, it has been shown that many patients are prescribed medication for obstructive lung disease without a relevant diagnosis or spirometry test registered. General practice characteristics have been reported to influence diagnosis and management of several chronic diseases. However, these findings are inconsistent, and it is uncertain whether practice characteristics influence spirometry testing among patients receiving medication for obstructive lung disease. The aim of this study was therefore to examine if practice characteristics are associated with spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease. METHODS: A national register-based cohort study was performed. All patients over 18 years receiving first-time prescriptions for medication targeting obstructive lung disease in 2008 were identified and detailed patient-specific data on sociodemographic status and spirometry tests were extracted. Information on practice characteristics like number of doctors, number of patients per doctor, training practice status, as well as age and gender of the general practitioners was linked to each medication user. RESULTS: Partnership practices had a higher odds ratio (OR) of performing spirometry compared with single-handed practices (OR 1.24, CI 1.09-1.40). We found a significant association between increasing general practitioner age and decreasing spirometry testing. This tendency was most pronounced among partnership practices, where doctors over 65 years had the lowest odds of spirometry testing (OR 0.25, CI 0.10-0.61). Training practice status was significantly associated with spirometry testing among single-handed practices (OR 1.40, CI 1.10-1.79). CONCLUSION: Some of the variation in spirometry testing among patients receiving first-time prescriptions for medication targeting obstructive lung disease was associated with practice characteristics. This variation in performance may indicate a potential for quality improvement.

The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer: results from the Nordic ACT trial.

PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting. METHODS: Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher's exact test. RESULTS: The VEGFR-1 319 C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p = 0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs. CONCLUSIONS: The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation.

Long-term use of antiplatelet drugs by stroke patients: a follow-up study based on prescription register data.

PURPOSE: Treatment with antiplatelet drugs is a key element of secondary stroke prevention. We investigated long-term antiplatelet drug use in stroke patients with a focus on non-persistence. METHODS: Population-based prescription register data were used to determine antiplatelet drug use in a cohort of stroke patients discharged from a Danish neurology department. The antiplatelet drugs comprised acetylsalicylic acid (ASA), clopidogrel and dipyridamole (if combined with ASA use). Non-persistence was defined as failure to present a prescription for antiplatelet drugs within 180 days after the dosage of a previous prescription had run out, or within 180 days after discharge. Cox regression was used to identify risk factors for non-persistence. RESULTS: The cohort comprised 503 patients with ischaemic stroke discharged in 1999-2001. During follow-up (median 2.8 years, interquartile range 0.8-7.8 years), 486 of the subjects presented prescriptions for antiplatelets. Most subjects used a dual regimen of ASA and dipyridamole (N = 320). Of 110 non-persistent subjects in this group, 64 stopped using ASA, but continued to use dipyridamole in monotherapy. Overall, 181 patients (36 %) were non-persistent. Stroke severity was inversely associated with the risk of non-persistence [NIHSS score on admission 0-3 (reference); 4-6: hazard risk (HR) 0.87, 95 % confidence interval (CI) 0.61-1.25; 7+: HR 0.47, 95 % CI 0.29-0.74]. CONCLUSIONS: Long-term non-persistence with antiplatelet treatment was high and more pronounced in our patients with less severe stroke. Our findings on the use of ASA and dipyridamole indicate that non-persistence may in part be amenable to simple intervention measures.