Jeanet W. Blom

Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study.

Summary.  Background: The incidence of venous thrombosis (VT) for cancer patients is increased compared with patients without cancer, but estimations of the incidence for different types of cancer have rarely been made because of the low incidence of various types of cancer. Large registries offer an opportunity to study the risk of VT in large cohorts of cancer patients, which is essential in decisions on prophylactic anti‐coagulant treatment. Methods: This cohort study estimates the incidence of VT in cancer patients by using record linkage of a Cancer Registry and an Anticoagulation Clinic database in the Netherlands. Cumulative incidences in patients with different types of malignancies were estimated. We calculated relative risks (RRs) in relation to the presence of distant metastases and treatment. Results: Tumors of the bone, ovary, brain, and pancreas are associated with the highest incidence of VT (37.7, 32.6, 32.1, and 22.7/1000/0.5 year). Patients with distant metastases had a 1.9‐fold increased risk [RRadj: 1.9; 95% confidence interval (CI): 1.6–2.3]. Chemotherapy leads to a 2.2‐fold increased risk (RRadj: 2.2; 95% CI: 1.8–2.7) and hormonal therapy leads to a 1.6‐fold increased risk (RRadj: 1.6; 95% CI: 1.3–2.1) compared with patients not using these treatment modalities. Patients with radiotherapy or surgery did not have an increased risk. Conclusions: We compared the overall incidences of VT in the first half year in our study to the risk of major bleeding as described in the literature. For patients with distant metastases, for several types of cancer, prophylactic anti‐thrombotic treatment could be beneficial.

Prevalence, determinants and patterns of multimorbidity in primary care: a systematic review of observational studies.

Introduction Multimorbidity is a major concern in primary care. Nevertheless, evidence of prevalence and patterns of multimorbidity, and their determinants, are scarce. The aim of this study is to systematically review studies of the prevalence, patterns and determinants of multimorbidity in primary care. Methods Systematic review of literature published between 1961 and 2013 and indexed in Ovid (CINAHL, PsychINFO, Medline and Embase) and Web of Knowledge. Studies were selected according to eligibility criteria of addressing prevalence, determinants, and patterns of multimorbidity and using a pretested proforma in primary care. The quality and risk of bias were assessed using STROBE criteria. Two researchers assessed the eligibility of studies for inclusion (Kappa  = 0.86). Results We identified 39 eligible publications describing studies that included a total of 70,057,611 patients in 12 countries. The number of health conditions analysed per study ranged from 5 to 335, with multimorbidity prevalence ranging from 12.9% to 95.1%. All studies observed a significant positive association between multimorbidity and age (odds ratio [OR], 1.26 to 227.46), and lower socioeconomic status (OR, 1.20 to 1.91). Positive associations with female gender and mental disorders were also observed. The most frequent patterns of multimorbidity included osteoarthritis together with cardiovascular and/or metabolic conditions. Conclusions Well-established determinants of multimorbidity include age, lower socioeconomic status and gender. The most prevalent conditions shape the patterns of multimorbidity. However, the limitations of the current evidence base means that further and better designed studies are needed to inform policy, research and clinical practice, with the goal of improving health-related quality of life for patients with multimorbidity. Standardization of the definition and assessment of multimorbidity is essential in order to better understand this phenomenon, and is a necessary immediate step.

The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma

Summary.  Background: Only limited data on the incidence of venous thrombosis in different types of malignancy are available. Patients with adenocarcinoma are believed to have the highest risk of developing venous thrombosis. Objectives: To study the incidence of thrombosis in patients with lung cancer, with an emphasis on the comparison between adenocarcinoma and squamous cell carcinoma, we have performed a cohort study of patients with non‐small‐cell lung cancer. In addition the risk associated with treatment and extent of disease was assessed. Patients/methods: A total of 537 patients with a first diagnosis of lung carcinoma were included. Patient and tumor characteristics as well as venous thrombotic events were recorded from the medical records and from the Anticoagulation Clinic. Results: Thrombotic risk in lung cancer patients was 20‐fold higher than in the general population (standardized morbidity ratio (SMR): 20.0 (14.6–27.4). In the group of patients with squamous cell cancer we found 10 (10/258) cases (incidence: 21.2 per 1000 years) of venous thrombosis whereas in the group of patients with adenocarcinoma 14 (14/133) cases (incidence: 66.7 per 1000 years) occured. The crude adjusted hazard ratio was 3.1 (95% CI: 1.4–6.9). The risk increased during chemotherapy and radiotherapy and in the presence of metastases. Conclusions: The risk of venous thrombosis in lung cancer patients is increased 20‐fold compared to the general population. Patients with adenocarcinoma have a higher risk than patients squamous cell carcinoma. During chemotherapy or radiotherapy and in the presence of metastases the risk is even higher.

Old and new risk factors for upper extremity deep venous thrombosis

Summary.  Background: Well known risk factors for upper extremity deep venous thrombosis are the presence of a central venous catheter (CVC) and malignancy, but other potential risk factors, such as surgery, injury and hormone replacement therapy (HRT), have not yet been explored. Methods: We performed a population‐based case‐control study including 179 consecutive patients, aged 18–70 years with upper extremity deep venous thrombosis and 2399 control subjects. Participants reported on acquired risk factors in a questionnaire and factor V Leiden and prothrombin 20210A mutation were ascertained. Information on CVC was obtained from discharge letters. Results: Forty‐two patients (23%) and one control subject (0.04%) had a CVC (ORadj: 1136, 95% CI: 153–8448, adjusted for age and sex). Cancer patients without a CVC had an eightfold increased risk of venous thrombosis of the arm (ORcrude: 7.7, 95% CI: 4.6–13.0). Other evident risk factors were prothrombotic mutations, surgery, immobilization of the arm (plaster cast), oral contraceptive use and family history, with odds ratios varying from 2.0 up to 13.1. The risk in the presence of injury and during puerperium was twofold or more increased, although not significantly. In contrast HRT, unusual exercise, travel and obesity did not increase the risk. Hormone users had an increased risk in the presence of prothrombotic mutations or surgery. Obese persons (BMI > 30 kg m−2) undergoing surgery had a 23‐fold increased risk of arm thrombosis compared with non‐obese persons not undergoing surgery. Conclusion: A CVC is a very strong risk factor for arm thrombosis. Most risk factors for thrombosis in the leg are also risk factors for arm thrombosis.

The Ariadne principles: how to handle multimorbidity in primary care consultations

Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient’s preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.Please see related article: http://www.biomedcentral.com/1741-7015/12/222.

Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection

OBJECTIVES To assess risk factors for fluoroquinolone resistance in community-onset febrile Escherichia coli urinary tract infection (UTI). METHODS A nested case-control study within a cohort of consecutive adults with febrile UTI presenting at primary healthcare centres or emergency departments during January 2004 through December 2009. Resistance was defined using EUCAST criteria (ciprofloxacin MIC >1.0 mg/L). Cases were subjects with fluoroquinolone-resistant E. coli, and controls those with fluoroquinolone-susceptible isolates. Multivariable logistic regression analysis was used to identify potential risk factors for fluoroquinolone resistance. RESULTS Of 787 consecutive patients, 420 had E. coli-positive urine cultures. Of these, 51 (12%) were fluoroquinolone resistant. Independent risk factors for fluoroquinolone resistance were urinary catheter [odds ratio (OR) 3.1; 95% confidence interval (CI) 0.9-11.6], recent hospitalization (OR 2.0; 95% CI 1.0-4.3) and fluoroquinolone use in the past 6 months (OR 17.5; 95% CI 6.0-50.7). Environmental factors (e.g. contact with animals or hospitalized household members) were not associated with fluoroquinolone resistance. Of fluoroquinolone-resistant strains, 33% were resistant to amoxicillin/clavulanate and 65% to trimethoprim/sulfamethoxazole; 14% were extended-spectrum β-lactamase (ESBL) positive compared with <1% of fluoroquinolone-susceptible isolates. CONCLUSIONS Recent hospitalization, urinary catheter and fluoroquinolone use in the past 6 months were independent risk factors for fluoroquinolone resistance in community-onset febrile E. coli UTI. Contact with animals or hospitalized household members was not associated with fluoroquinolone resistance. Fluoroquinolone resistance may be a marker of broader resistance, including ESBL positivity.

The contribution of immobility risk factors to the incidence of venous thrombosis in an older population.

Venous thrombosis is common in the older population. Assessment of risk factors is necessary to implement preventive measures.

Blood pressure trends and mortality: the Leiden 85-plus Study.

Objective: To evaluate the independent contributions of both the trend in SBP and the SBP value at age 90 to the prediction of mortality in nonagenarians. Methods: The trend in SBP between 85 and 90 years and SBP at age 90 years were assessed in a population-based sample of 271 participants (74 men and 197 women) aged 90 years of the Leiden 85-plus Study, an observational population-based prospective follow-up study (started 1997). Primary endpoint, followed up over 5 years (median 3.6 years), was all-cause mortality. Results: A decreasing trend in SBP between 85 and 90 years (decline ≥2.9 mmHg/year) was associated with increased mortality compared to an average SBP trend (hazard ratio 1.45, 95% confidence interval 1.02–2.06), independent of SBP at age 90. The effect was stronger in institutionalized participants compared to those living independently [hazard ratio 1.87 (1.10–3.19) and hazard ratio 1.30 (0.81–2.09)]. After analysis with a fully adjusted model, the estimate approached unity [hazard ratio 1.08 (0.60–1.86)]. Overall, 90-year-old participants with SBP of 150 mmHg or less had a 1.62 times increased mortality risk compared to those with SBP more than 150 mmHg (1.21–2.20), independent of the SBP trend in preceding years. This applied to those with and without antihypertensive drugs and those with and without history of cardiovascular disease or noncardiovascular disease. In the fully adjusted model, the estimate was 1.47 (0.90–2.40). Conclusion: In very old age, both decreasing trend in SBP over the previous 5 years and the current SBP value independently contribute to prediction of all-cause mortality. Therefore, in individual patients, all available preceding SBP measurements should be taken into account.

Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment.

OBJECTIVE Home-based treatment of acute pyelonephritis (AP) is generally reserved for young non-pregnant women who lack co-morbidity. This study, focusing on the elderly and patients with co-morbidity, evaluates the Dutch primary care guideline that recommends referral to hospital only in case of suspected deterioration to severe sepsis or failure of antibiotic treatment, irrespective of patients age, sex or co-morbidity. METHODS A prospective observational cohort study including consecutive non-pregnant adults with AP. Clinical and microbiological outcome measures of non-referred patients from 35 primary health care centres (PHC) were compared to patients referred to two affiliating emergency departments (EDs). RESULTS Of 395 evaluable patients, 153 were treated by PHCs and 242 referred to EDs. The median age was 63years [IQR 43-77], 34% were male, 58% had co-morbidity; all comparable between the PHC and ED group. Referred ED patients were more likely to have signs of sepsis and to have been pre-treated with antibiotics. Bacteraemia was present in 10% of patients in the PHC group and 27% in the ED group (RR 2.83; 95% CI: 1.64-4.86, p<0.001). Eight (5%) PHC patients were admitted during outpatient treatment but otherwise no major complications occurred. Clinical failure rates at 30days were similar between PHC patients and ED patients; 9% and 10% respectively. Mortality rates of PHC patients versus ED patients were 1% versus 5% at 30days (p=0.058) and 1% versus 7% at 90days (p=0.007). Complicated outcome occurred in 6% of the PHC patients versus 12% in the patients referred to ED (p=0.067). CONCLUSION In a health care system with a well-organized primary care system and clear guideline, the outcome of adults with acute pyelonephritis, including men, the elderly and patients with co-morbidity, selected for oral antibiotic treatment at home did not lead to major complications.

Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85-plus Study

To investigate whether low systolic blood pressure is predictive for increased mortality risk in 90‐year‐old subjects without heart failure, defined by low levels of NT‐proBNP, as well as in 90‐year‐old subjects with high levels of NT‐proBNP.