Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women.

BACKGROUND: Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. OBJECTIVES: We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. METHODS: Premenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up. RESULTS: Six hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1). CONCLUSION: CHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

Recruitment and retention of general practitioners in European medical deserts: a systematic review.

INTRODUCTION: Despite policies aiming at universal health coverage by ensuring availability and accessibility of general practitioners (GPs), medically underserved areas are still present in Europe. This systematic review aims to summarize and compare literature on interventions and their potential effectiveness of GP recruitment and retention in these underserved areas ('medical deserts') from 2011 onwards. METHODS: PubMed and Embase were used to identify publications, applying a two-stage selection process. All types of study designs, published in the past 10 years, were included if they discussed a possible intervention for GP recruitment or retention covering an underserved area in an EU-27/EEA/EFTA country (part of the European Union, the European Economic Area or the European Free Trade Association). Exclusion criteria were abstracts or full text not available, conference abstracts, poster presentations, books or overlapping secondary literature. Identified interventions were classified into four categories: 'education', 'professional and personal support', 'financial incentives' and 'regulation'. Eligible articles were critically appraisal by two authors (JB, LF), independently, by using the Joanna Briggs Institute checklist. RESULTS: Of the 294 publications initially retrieved, 25 publications were included. Of them, 14 (56%) described educational interventions, 13 (52%) professional and personal support, and 11 (40%) financial or regulatory interventions. Overlapping categories were often described (56%). The effectiveness of educational or supportive interventions has mainly been evaluated cross-sectionally, whereby causal inference on future GP availability cannot be implied. Few and mixed results were found for the effectiveness of financial and regulatory interventions, because period co-interventions were not taken into account during the study. CONCLUSION: In the past 10 years, educational and supportive interventions to improve GP recruitment and retention have been reported most frequently, but often overlapping strategies are seen. While multiple strategies have potential to be effective, their limited evaluation makes it difficult to provide suggestions for policymakers to adapt their GP recruitment and retention strategies aiming at a best-practice approach in European medical deserts.

Characteristics of medical deserts and approaches to mitigate them: a scoping review.

INTRODUCTION: Medical deserts are increasingly considered problematic and many countries employ a multitude of actions and initiatives to achieve a better distribution of the health workforce (HWF). This study systematically maps research and provides an overview of the definitions/characteristics of medical deserts. It also identifies contributing factors and approaches to mitigate medical deserts. METHODS: Embase, MEDLINE, CINAHL, Web of Science Core Collection, Google Scholar and The Cochrane Library were searched from inception to May 2021. Studies reporting primary research on definitions, characteristics, contributing factors and approaches to mitigate medical deserts were included. Two independent reviewers assessed studies for eligibility, extracted data and clustered studies. RESULTS: Two-hundred and forty studies were included (49% Australia/New Zealand, 43% North America, 8% Europe). All used observational designs except for five quasi-experimental studies. Studies provided definitions (n=160), characteristics (n=71), contributing/associated factors (n=113), and approaches to mitigate medical deserts (n=94). Most medical deserts were defined by the density of the population in an area. Contributing/associated factors consisted in sociodemographic/characteristics of HWF (n=70), work-related factors (n=43) and lifestyle conditions (n=34). Approaches focused on training adapted to the scope of rural practice (n=79), HWF distribution (n=3), support and infrastructure (n=6) and innovative models of care (n=7). DISCUSSION: Our study provides the first scoping review on definitions, characteristics, contributing/associated factors and approaches to mitigate medical deserts. We identified gaps such as the scarcity of longitudinal studies to investigate factors contributing to medical deserts, and interventional studies to evaluate the effectiveness of approaches to mitigate medical deserts.

Characteristics of Medical Deserts and Approaches to Mitigate Their Health Workforce Issues: A Scoping Review of Empirical Studies in Western Countries.

BACKGROUND: Medical deserts are considered a problematic issue for many Western countries which try to employ multitude of policies and initiatives to achieve a better distribution of their health workforce (HWF). The aim of this study was to systematically map research and provide an overview of definitions, characteristics, contributing factors and approaches to mitigate medical deserts within the European Union (EU)-funded project "ROUTE-HWF" (a Roadmap OUT of mEdical deserts into supportive Health WorkForce initiatives and policies). METHODS: We performed a scoping review to identify knowledge clusters/research gaps in the field of medical deserts focusing on HWF issues. Six databases were searched till June 2021. Studies reporting primary research from Western countries on definitions, characteristics, contributing factors, and approaches were included. Two independent reviewers assessed studies for eligibility, extracted data and clustered studies according to the four defined outcomes. RESULTS: Two-hundred and forty studies were included (n=116, 48% Australia/New Zealand; n=105, 44% North America; n=20, 8% Europe). All used observational designs except for five quasi-experimental studies. Studies provided definitions (n=171, 71%), characteristics (n=95, 40%), contributing factors (n=112, 47%), and approaches to mitigate medical deserts (n=87, 36%). Most medical deserts were defined by the density of the population in an area. Contributing factors to HWF issues in medical deserts consisted in work-related (n=55, 23%) and lifestyle-related factors (n=33, 14%) of the HWF as well as sociodemographic characteristics (n=79, 33%). Approaches to mitigate them focused on training adapted to the scope of rural practice (n=67, 28%), HWF distribution (n=3, 1%), support/infrastructure (n=8, 3%) and innovative models of care (n=7, 3%). CONCLUSION: Our study provides the first scoping review that presents and categorizes definitions, characteristics, contributing factors, and approaches to mitigate HWF issues in medical deserts. We identified gaps such as the scarcity of longitudinal studies to investigate the impact of factors contributing to medical deserts, and interventional studies to evaluate the effectiveness of approaches to mitigate HWF issues.

Adherence to coprescribing of laxatives with opioids and associated characteristics in general practices in the Netherlands.

BACKGROUND: Guidelines recommend to prescribe a laxative with an opioid to prevent constipation. We aimed to determine the adherence by general practitioners (GPs) to this recommendation and to explore which GP- and patient related factors were associated with it from the perspective of the GP.  METHODS: We conducted an observational study using GPs' prescription data from the Nivel Primary Care Database combined with a questionnaire asking for reasons of non-adherence. The proportion of first opioid prescriptions prescribed together with a laxative was determined as primary outcome. Possible explanatory factors such as the quality of registration, the level of collaboration with the pharmacy, familiarity with the recommendation and use of a clinical decision support system were explored, as were the self-reported reasons for non-adherence (classified as either GP-related or patient-related). We assessed the association of factors with the primary outcome using univariable multilevel logistic regression analysis. RESULTS: The recommendation was measured in 195 general practices. The median proportion of first opioid prescriptions prescribed together with a laxative in these practices was 54% (practice range 18-88%). None of the determinants was consistently associated with the primary outcome. GPs from 211 practices filled out the questionnaire and the most frequently mentioned reason not to prescribe a laxative was that the patient has laxatives in stock, followed by that the patient doesn't want a laxative; both were patient-related factors. CONCLUSION: There was room for improvement in following the guideline on laxative prescribing in opioid use. A main reason seemed to be that the patient refuses a laxative. Improvement measures should therefore focus on communication between GPs and patients on the relevance of co-using a laxative with opioids. Future studies need to establish the effect of such improvement measures, and determine whether reasons for non-adherence to the guideline changed over time.

The use of out-of-hours primary care during the first year of the COVID-19 pandemic.

BACKGROUND: In the Netherlands, General Practitioners (GP) are usually the first point of contact with a health professional for most health problems. Out-of-hours (OOH) primary care is provided by regional OOH services. Changes in consultation rates at OOH services may be regarded as a warning system for failures elsewhere in the healthcare system. Therefore in this study, we investigated how the COVID-19 pandemic changed the use of primary care OOH services during the first year of the pandemic. METHODS: Routine electronic health records data were used from 60% of OOH services in the Netherlands, collected by the Nivel Primary Care Database. We compared consultation rates per week (2020) for COVID-19-like symptoms and other health problems (e.g. small traumas, urinary tract infections), for different age groups, the proportion of remote consultations, and different levels of urgency during the pandemic compared to the same period in 2019. RESULTS: The number of consultations for COVID-19-like symptoms peaked at the start of the COVID-19 pandemic, while consultations for other health problems decreased. These changes in consultation rates differed between age groups. Remote consultations took place more frequently for all health problems, while the proportion of non-urgent health problems increased. CONCLUSION: There were significant changes in the number of consultations and the proportion that were remote for COVID-19-like symptoms and other health problems. Especially care for babies and young children decreased, while the number of consultations for older adults remained stable. The continued use of OOH services by older adults suggests there were unmet care needs elsewhere in our healthcare system.

Electronic Health Record-Triggered Research Infrastructure Combining Real-world Electronic Health Record Data and Patient-Reported Outcomes to Detect Benefits, Risks, and Impact of Medication: Development Study.

BACKGROUND: Real-world data from electronic health records (EHRs) represent a wealth of information for studying the benefits and risks of medical treatment. However, they are limited in scope and should be complemented by information from the patient perspective. OBJECTIVE: The aim of this study is to develop an innovative research infrastructure that combines information from EHRs with patient experiences reported in questionnaires to monitor the risks and benefits of medical treatment. METHODS: We focused on the treatment of overactive bladder (OAB) in general practice as a use case. To develop the Benefit, Risk, and Impact of Medication Monitor (BRIMM) infrastructure, we first performed a requirement analysis. BRIMM's starting point is routinely recorded general practice EHR data that are sent to the Dutch Nivel Primary Care Database weekly. Patients with OAB were flagged weekly on the basis of diagnoses and prescriptions. They were invited subsequently for participation by their general practitioner (GP), via a trusted third party. Patients received a series of questionnaires on disease status, pharmacological and nonpharmacological treatments, adverse drug reactions, drug adherence, and quality of life. The questionnaires and a dedicated feedback portal were developed in collaboration with a patient association for pelvic-related diseases, Bekkenbodem4All. Participating patients and GPs received feedback. An expert meeting was organized to assess the strengths, weaknesses, opportunities, and threats of the new research infrastructure. RESULTS: The BRIMM infrastructure was developed and implemented. In the Nivel Primary Care Database, 2933 patients with OAB from 27 general practices were flagged. GPs selected 1636 (55.78%) patients who were eligible for the study, of whom 295 (18.0% of eligible patients) completed the first questionnaire. A total of 288 (97.6%) patients consented to the linkage of their questionnaire data with their EHR data. According to experts, the strengths of the infrastructure were the linkage of patient-reported outcomes with EHR data, comparison of pharmacological and nonpharmacological treatments, flexibility of the infrastructure, and low registration burden for GPs. Methodological weaknesses, such as susceptibility to bias, patient selection, and low participation rates among GPs and patients, were seen as weaknesses and threats. Opportunities represent usefulness for policy makers and health professionals, conditional approval of medication, data linkage to other data sources, and feedback to patients. CONCLUSIONS: The BRIMM research infrastructure has the potential to assess the benefits and safety of (medical) treatment in real-life situations using a unique combination of EHRs and patient-reported outcomes. As patient involvement is an important aspect of the treatment process, generating knowledge from clinical and patient perspectives is valuable for health care providers, patients, and policy makers. The developed methodology can easily be applied to other treatments and health problems.

Fitness for purpose of routinely recorded health data to identify patients with complex diseases: The case of Sjögren's syndrome.

BACKGROUND: This study is part of the EU-funded project HarmonicSS, aimed at improving the treatment and diagnosis of primary Sjögren's syndrome (pSS). pSS is an underdiagnosed, long-term autoimmune disease that affects particularly salivary and lachrymal glands. OBJECTIVES: We assessed the usability of routinely recorded primary care and hospital claims data for the identification and validation of patients with complex diseases such as pSS. METHODS: pSS patients were identified in primary care by translating the formal inclusion and exclusion criteria for pSS into a patient selection algorithm using data from Nivel Primary Care Database (PCD), covering 10% of the Dutch population between 2006 and 2017. As part of a validation exercise, the pSS patients found by the algorithm were compared to Diagnosis Related Groups (DRG) recorded in the national hospital insurance claims database (DIS) between 2013 and 2017. RESULTS: International Classification of Primary Care (ICPC) coded general practitioner (GP) contacts combined with the mention of "Sjögren" in the disease episode titles, were found to best translate the formal classification criteria to a selection algorithm for pSS. A total of 1462 possible pSS patients were identified in primary care (mean prevalence 0.7‰, against 0.61‰ reported globally). The DIS contained 208 545 patients with a Sjögren related DRG or ICD10 code (prevalence 2017: 2.73‰). A total of 2 577 577 patients from Nivel PCD were linked to the DIS database. A total of 716 of the linked pSS patients (55.3%) were confirmed based on the DIS. CONCLUSION: Our study finds that GP electronic health records (EHRs) lack the granular information needed to apply the formal diagnostic criteria for pSS. The developed algorithm resulted in a patient selection that approximates the expected prevalence and characteristics, although only slightly over half of the patients were confirmed using the DIS. Without more detailed diagnostic information, the fitness for purpose of routine EHR data for patient identification and validation could not be determined.

Prevalence and incidence rate of hospital admissions related to medication between 2008 and 2013 in The Netherlands.

PURPOSE: In 2009 a Dutch guideline was published containing recommendations to reduce Hospital Admissions Related to Medications (HARMs). This study aims to examine time-trends of HARMs and their potential preventability between 2008 and 2013 in The Netherlands. METHODS: A retrospective prevalence study was conducted using the Dutch PHARMO Database Network. A semi-automated pre-selection was used to make a crude identification of possible HARMs of which four samples were selected. These were independently assessed with respect to causality and potential preventability by a physician and pharmacist. The results were stratified by age into 18-64 years and 65 years and older. For these groups the net prevalences and incidence rates of HARMs and potentially preventable HARMs were calculated for the years 2008, 2009, 2011 and 2013. RESULTS: Four samples of 467 (2008), 447 (2009), 446 (2011) and 408 (2013) admissions were assessed. The net prevalence of HARMs in the 18-64 years group was approximately four times smaller compared to the older group with a mean prevalence of 2.7% (95% confidence interval [CI]:2.4%-3.0%) and 10.2% (95%CI: 9.7%-10.7%) respectively. The potential preventability was 25.1% (18.4%-31.8%) and 48.3% (95%CI: 44.8%-51.8%), respectively. The prevalence of HARMs in both groups did not change significantly between 2008 and 2013 with 2.4% (95%CI: 1.9%-3.0%) and 10.0% (95%CI: 9.0%-11.0%) in 2008 and 3.1% (2.7%-3.5%) and 10.4% (95%CI: 9.4%-11.4%) in 2013, respectively. CONCLUSION: Despite efforts to reduce HARMs, the prevalence did not decrease over time. Additional measures are therefore necessary, especially in the elderly population.

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study.

Background: Patients with primary hypothyroidism are treated with levothyroxine (LT4) to normalize their serum thyrotropin (TSH). Finding the optimal dosage is a long-lasting process, and a small change can have major impact. Currently, limited data are available on the impact of dose-equivalent substitution between brands. This study aimed to determine the effect of the shortage of the LT4 brand Thyrax® in the Netherlands and the resulting dose-equivalent switch to another brand on plasma TSH concentrations in a large cohort of patients. Methods: Observational cohort study. Two registries representative for the Dutch population containing prescription and laboratory test data: the Nivel Primary Care Database and the PHARMO Database Network. Patients using at least 25 µg Thyrax daily for one year or longer were included. Two cohorts were formed: a switch cohort consisting of patients who switched from Thyrax to an alternative brand, and a Thyrax cohort including patients who continued to use Thyrax. Patients in the switch cohort did switch from Thyrax to a different brand of LT4 in 2016 and had two consecutive TSH measurements on the same dose of LT4, one before and one 6 weeks after the switch. Patients in the Thyrax cohort had two consecutive TSH measurements on the same dose of Thyrax that were 6 weeks apart. Results: In the Thyrax cohort, 19% of euthyroid patients using ≤100 µg had a TSH level outside the reference range at the subsequent measurement compared with 24% in the switch cohort (p < 0.0001). For patients using >100 µg Thyrax, these figures were 24% and 63%, respectively (p < 0.0001). Furthermore, patients using >50 µg Thyrax were four to five times more likely to become hyperthyroid after a dose-equivalent switch to a different brand compared with patients who stayed on Thyrax. Conclusions: In euthyroid patients continuing the LT4 product Thyrax at the same dose, TSH was out of range in 19-24% at least 6 weeks later. A dose-equivalent switch from Thyrax to other LT4 brands induced biochemical signs of overdosing in an even larger proportion (24-63%) of patients. The results indicate that a dose-equivalent LT4 brand switch may necessitate a dose adjustment in a large number of patients.

Impact of a Restriction in Reimbursement on Proton Pump Inhibitors in Patients with an Increased Risk of Gastric Complications.

Governments have several options to reduce the increasing costs of health care, including restrictions for the reimbursement of medicines. Next to the intended effect of reduced costs for medicines, reimbursement restriction can have unintended effects such as patients refraining from their treatment which may lead to health problems and increased use of health care. An example of a reimbursement restriction is the one for proton pump inhibitors (PPIs) that became effective in the Netherlands in January 2012. A major unintended effect of this measure could be that high-risk patients who start with non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (aspirin) and who have an increased risk of gastric complications for which they are prescribed PPIs refrain from this PPI treatment. The aim of this study was to evaluate the effect of the reimbursement restriction among high-risk users of NSAIDs or aspirin. Do these patients refrain from their PPI treatment and if so do they have an increased risk of gastric complications? Part of the patients starting with NSAIDs or aspirin have an increased risk of gastric complications due to their age, comorbidities, or co-medication. The incidence of PPI use during the 2 years before the reimbursement restriction (2010 and 2011) and 2 years after the introduction of the reimbursement restriction was compared for patients on NSAIDs or aspirin with an increased risk of developing gastric complications. Impact of age, sex, and social economic status (SES) was taken into account. Hospital admissions due to gastric complications were studied over the same period (2010-2013). Data were obtained from a large population-based primary care database and a hospital database. The use of PPIs in patients with an increased risk of gastric complications who started NSAID/aspirin increased from 40% in 2010 to 55% in 2013. No impact was found of age, sex, or SES. There was no increase in hospital admissions due to gastric complications after the reimbursement restriction. The reimbursement restriction on PPIs was not associated with any detectable unintended effects for patients with an increased risk of gastric complications.

Evaluation of the Prevention and Reactivation Care Program (PreCaP) for the hospitalized elderly: a prospective nonrandomized controlled trial.

BACKGROUND: The hospitalized elderly are at risk of functional decline. We evaluated the effects and care costs of a specialized geriatric rehabilitation program aimed at preventing functional decline among at-risk hospitalized elderly. METHODS: The prospective nonrandomized controlled trial reported here was performed in three hospitals in the Netherlands. One hospital implemented the Prevention and Reactivation Care Program (PReCaP), while two other hospitals providing usual care served as control settings. Within the PReCaP hospital we compared patients pre-implementation with patients post-implementation of the PReCaP ("within-hospital analysis"), while our nonrandomized controlled trial compared patients of the PReCaP hospital post-implementation with patients from the two control hospitals providing usual care ("between-hospital analysis"). Hospitalized patients 65 years or older and at risk of functional decline were interviewed at baseline and at 3 and 12 months using validated questionnaires to score functioning, depression, and health-related quality of life (HRQoL). We estimated costs per unit of care from hospital information systems and national data sources. We used adjusted general linear mixed models to analyze functioning and HRQoL. RESULTS: Between-hospital analysis showed no difference in activities of daily living (ADL) or instrumental activities of daily living (IADL) between PReCaP patients and control groups. PReCaP patients did have slightly better cognitive functioning (Mini Mental State Examination; 0.4 [95% confidence interval (CI) 0.2-0.6]), lower depression (Geriatric Depression Scale 15; -0.9 [95% -1.1 to -0.6]) and higher perceived health (Short-Form 20; 5.6 [95% CI 2.8-8.4]) than control patients. Analyses within the PReCaP hospital comparing patients pre-and post-implementation of the PReCaP showed no improvement over time in functioning, depression, and HRQoL. One-year health care costs were higher for PReCaP patients, both for the within-hospital analysis (+€7,000) and the between-hospital analysis (+€2,500). CONCLUSION: We did not find any effect of the PReCaP on ADL and IADL. The PReCaP may possibly provide some benefits to hospitalized patients at risk of functional decline with respect to cognitive functioning, depression, and perceived health. Further evaluations of integrated intervention programs to limit functional decline are therefore required.

Genetic variations associated with recurrent venous thrombosis.

BACKGROUND: The prediction of recurrent venous thrombosis using individual genetic risk predictors has proven to be challenging. The aim of this study was to assess whether multiple genetic single nucleotide polymorphism (SNP) analysis would predict recurrent venous thrombosis. METHODS AND RESULTS: Patients with a first venous thrombosis were followed for a recurrent venous thrombosis up to 2009 (MEGA follow-up study), which occurred in 608 out of 4100 patients (2.7%/year). Thirty-one common thrombosis-associated single nucleotide polymorphisms (SNPs) were associated with the risk of recurrence. A genetic risk score (GRS) for each individual was calculated by summing the number of risk-increasing alleles for each of the 31 SNPs and for a simplified model consisting of 5 SNPs: rs6025, rs1799963, rs8176719, rs2066865, and rs2036914. The risk of recurrence associated with the GRS was calculated continuously and after stratification in a low and high score. All individual SNPs were at most mildly associated with recurrence risk. Regarding the 31-SNP GRS, recurrence risk was highest in patients with ≥31 and lowest in patients with <21 risk alleles. The discriminative power of the 5-SNP GRS was similar to that of the 31-SNP GRS. The 6-year cumulative incidence of recurrence was high for individuals with ≥5 (20.3%; 95% confidence interval, 16.5-24.1) and low for individuals with ≤1 (9.4%; 95% confidence interval, 6.7-12.1) risk alleles. Predictive power improved after stratification into provoked and unprovoked first events and sex. CONCLUSIONS: Multiple genetic SNP analysis is useful in the prediction of recurrent thrombosis, even more so when combining this model with clinical risk factors.

Formal and informal care costs of hospitalized older people at risk of poor functioning: A prospective cohort study.

Hospitalized older people are at risk of poor functioning after hospital discharge. We aimed to relate formal and informal care costs to level of risk for low functioning of hospitalized older people up to one year after admission. We studied 460 patients 65 years or older who were admitted to a 450-bed hospital in the Netherlands between June 2010 and October 2010. Participants were classified into five risk groups at hospital admission using the Identification Seniors At Risk-Hospitalized Patients (ISAR-HP). Patients were interviewed at hospital admission and at three and twelve months after admission using validated questionnaires to measure health care utilization. Informal caregivers were interviewed by mailed paper questionnaires at the same time as patients. We estimated costs per unit from hospital information systems and nationally representative research. Mean healthcare costs were €30k euro per person per year, with one third for initial hospital stay (€9,8k), one third for formal healthcare costs between hospital discharge and twelve month follow up (€10,3k), and one third for informal healthcare costs between hospital discharge and twelve month follow up (€9,5k). Informal and formal healthcare costs were almost double for people with the highest risk score compared to people not at risk (p<0.001). Older patients with high risk scores at hospital admission have substantially higher formal and informal care costs in the year after initial hospital admission than people with low risk scores. This implies that substantial investments may be made in preventive interventions for at-risk hospitalized older people.

Impact of incident venous thromboembolism on risk of arterial thrombotic diseases.

BACKGROUND: Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population. METHODS AND RESULTS: In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69-6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32-3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients. CONCLUSIONS: Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE.

Prognosis of hospitalised older people with different levels of functioning: a prospective cohort study.

BACKGROUND: hospitalised older people are at risk for poor functioning after hospital discharge. We aimed to validate the predictive ability of the Identification Seniors At Risk-Hospitalized Patients (ISAR-HP) screening questionnaire to identify older patients at risk for functional dependence by comparing groups with different ISAR-HP scores on cognitive and physical functioning, mortality, health-related quality of life (HRQoL) and loneliness. DESIGN: a longitudinal prospective cohort study. SETTING: a 450-bed hospital in the Netherlands. SUBJECTS: four hundred and sixty patients 65 years or older admitted between June 2010 and October 2010. METHODS: participants were classified into five risk groups at hospital admission using the ISAR-HP. We interviewed patients at hospital admission and at 3 and 12 months after admission using validated questionnaires to score HRQoL, physical functioning, cognitive functioning and loneliness. Differences in survival were quantified by a concordance statistic (c). RESULTS: cognitive functioning, physical functioning, loneliness and HRQoL differed significantly between groups during the 1-year follow-up after hospital admission (all comparisons P < 0.05), with high-risk groups having lower scores than low-risk groups for functioning and loneliness, although not always for HRQoL. The lowest risk group (ISAR-HP = 0) scored consistently higher on functioning and HRQoL than all other groups. Mortality differed significantly between groups (P < 0.001, c = 0.67). CONCLUSIONS: the ISAR-HP can readily distinguish well-functioning older patients from patients with low functioning and low HRQoL after hospital admission. The ISAR-HP may hence assist in selecting patients who may benefit from individually tailored reactivation treatment that is provided next to treatment of their medical condition.

Surveillance of second-degree relatives from melanoma families with a CDKN2A germline mutation.

BACKGROUND: Lifetime melanoma risk of mutation carriers from families with a germline mutation in the CDKN2A gene is estimated to be 67%. The necessity to include family members in a melanoma surveillance program is widely endorsed, but there is no consensus on which family members should be invited. METHODS: In a retrospective follow-up study, we investigated the yield of surveillance of first- and second-degree relatives of melanoma and pancreatic cancer patients from 21 families with the "p16-Leiden" CDKN2A mutation. Melanoma incidence rates were compared with the general population. RESULTS: Three-hundred and fifty-four first-degree relatives and 391 second-degree relatives were included. Forty-five first-degree relatives and 11 second-degree relatives were diagnosed with melanoma. Most (72%) of second-degree relatives diagnosed with melanoma had become a first-degree relative before diagnosis, due to the occurrence of a melanoma in a parent or sibling. Overall, melanoma incidence rate was 2.1 per 1,000 person years [95% confidence interval (CI), 1.2-3.8] in family members still being second-degree relatives at diagnosis, compared with 9.9 per 1,000 person years (95% CI, 7.4-13.3) in first-degree relatives. The standardized morbidity ratio for melanoma of second-degree relatives compared with the general population was 12.9 (95% CI, 7.2-23.4). CONCLUSION: Second-degree relatives from families with the p16-Leiden mutation in CDKN2A have a considerably increased melanoma risk compared with the general population. IMPACT: This study provides justification for the surveillance of second-degree relatives from families with a CDKN2A germline mutation.

Increased risk of CVD after VT is determined by common etiologic factors.

Patients with venous thrombosis (VT) have an increased risk of subsequent CVD (CVD), but the underlying pathophysiology is unclear. Using data from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis follow-up study, 4480 patients with VT, 2926 partner control participants, and 2638 random digit dialing (RDD) control participants were followed-up between 1999 and 2008. Incidence rates and hazard ratios with 95% confidence intervals (95% CIs) of CVD (defined as myocardial infarction or ischemic stroke) were calculated for patients vs controls. Measurable confounders (age, sex, body mass index, smoking, chronic disease, malignancy, genetic thrombophilia, and procoagulant markers) were adjusted for when comparing patients with RDD controls. Unmeasured lifestyle-related factors were also considered by comparing patients with their partners. During a median follow-up time of 5 years, 124 CVD events occurred. Incidence of CVD per 1000 person-years was 3.2 (95% CI, 2.5-4.0) in patients, 2.2 (95% CI, 1.5-3.0) in partners, and 1.6 (95% CI, 0.9-2.6) in RDD controls. Crude hazard ratio was 2.2 (95% CI, 1.2-3.8) in patients compared with RDD controls and 1.5 (95% CI, 1.0-2.3) in patients compared with partners. After adjustment for all confounders, these risks attenuated to 1.8 (95% CI, 0.8-4.2) and 1.3 (95% CI, 0.7-2.5) for patients compared with RDD control participants and partners, respectively. In conclusion, individuals with VT had an increased risk of CVD. This could be explained by common etiologic factors.

Broadening the factor V Leiden paradox: pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum.

Risk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.