Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus.

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.

Incidence of sight-threatening diabetic retinopathy in people with Type 2 diabetes mellitus and numbers needed to screen: a systematic review.

AIM: To investigate the incidence of sight-threatening diabetic retinopathy in Type 2 diabetes mellitus. BACKGROUND: In most countries, yearly or biennial screening intervals for diabetic retinopathy in people with Type 2 diabetes are recommended. Fewer screening sessions reduce the effort required of people with Type 2 diabetes and reduce healthcare costs. METHODS: We conducted a search of PubMed, Embase, Web of Science and the COCHRANE Library for studies published betweeen 1 January 2000 and 1 January 2017. Eligible studies were those that included general populations of >100 people with Type 2 diabetes mellitus. Additional study population criteria were absence of moderate diabetic retinopathy or more severe diabetic retinopathy at last screening session and at least two gradable retinal screening sessions. Outcomes of interest in the included studies were moderate and severe non-proliferative diabetic retinopathy (R2), proliferative diabetic retinopathy (R3) or maculopathy (M1), collectively known as sight-threatening or referable diabetic retinopathy. RESULTS: A total of 17 studies were included. In people with Type 2 diabetes without or with only mild diabetic retinopathy at baseline, the average incidence rates of sight-threatening diabetic retinopathy were ~1 per 100 person-years and ~8 per 100 person-years, respectively. The average numbers needed to screen to detect one case of sight-threatening diabetic retinopathy were 175 and 19 in people without and with mild retinopathy at last screening, respectively. CONCLUSION: In people with Type 2 diabetes without retinopathy at last screening, the incidence of severe sight-threatening retinopathy at the subsequent screening session was low. In people with mild retinopathy, progression to sight-threatening diabetic retinopathy was nearly 10-fold higher. This review supports lengthening of the screening interval of patients with Type 2 diabetes without retinopathy at last screening session.

The frail older person does not exist: development of frailty profiles with latent class analysis.

BACKGROUND: A fundamental issue in elderly care is targeting those older people at risk and in need of care interventions. Frailty is widely used to capture variations in health risks but there is no general consensus on the conceptualization of frailty. Indeed, there is considerable heterogeneity in the group of older people characterized as frail. This research identifies frailty profiles based on the physical, psychological, social and cognitive domains of functioning and the severity of the problems within these domains. METHODS: This research was a secondary data-analysis of older persons derived from The Older Person and Informal Caregiver Minimum Dataset. Selected respondents were 60 years and older (n = 43,704; 59.6% female). The following variables were included: self-reported health, cognitive functioning, social functioning, mental health, morbidity status, and functional limitations. Using latent class analysis, the population was divided in subpopulations that were subsequently discussed in a focus group with older people for further validation. RESULTS: We distinguished six frailty profiles: relatively healthy; mild physically frail; psychologically frail; severe physically frail; medically frail and multi-frail. The relatively healthy had limited problems across all domains. In three profiles older people mostly had singular problems in either the physical or psychological domain and the severity of the problems differed. Two remaining profiles were multidimensional with a combination of problems that extended to the social and cognitive domains. CONCLUSIONS: Our research provides an empirical base for meaningful frailty profiles. The profiles showed specific patterns underlying the problems in different domains of functioning. The heterogeneous population of frail older people has differing needs and faces different health issues that should be considered to tailor care interventions. Evaluation research of these interventions should acknowledge the heterogeneity of frailty by profiling.

General practitioners' and community pharmacists' beliefs and practices on opioids for non-malignant pain.

BACKGROUND: In Europe, opioid use has surged, largely due to prescriptions for chronic non-malignant pain (CNMP). General practitioners (GPs) and community pharmacists (CPs) play a major role in opioid prescribing for non-malignant pain. Exploring their personal beliefs and practices might reveal underlying mechanisms to identify measures that could halt the further escalation of opioid use. METHODS: Guided by the health belief model, a survey was designed and distributed nationwide to examine the practices and beliefs of GPs and CPs in the domains: threats, benefits, barriers and self-efficacy. The results of GPs and CPs were compared at the statement level using chi-square analysis. RESULTS: Of 214 GPs and 212 CPs who completed the survey, the majority agreed that too many opioids are used in the treatment of chronic non-malignant pain (66.8% GPs and 66.5% CPs). Furthermore, they were concerned about the addictive potential of opioids (83.1% GPs and 71.7% CPs). In general, both professions have concerns about opioid use. GPs report a slightly higher degree of self-efficacy and perceive fewer benefits from opioids in treating CNMP. GPs and CPs valued the recommended measures to reduce opioid prescribing, yet less than half actively implement these strategies in their clinics. CONCLUSION: GPs and CPs believe that opioids are being used too frequently to treat CNMP. However, both professions lack the actions to improve opioid-related care. GPs and CPs require education, collaboration and tools to implement guidelines on non-malignant pain and opioids. SIGNIFICANCE: This study, guided by the health belief model, reveals that general practitioners and community pharmacists have serious concerns about opioid use in chronic non-malignant pain. Despite shared concerns, both professions differ in their beliefs about opioid benefits and perceived self-efficacy. Both professions have in common that they value recommended measures to reduce opioid prescribing. Also, they both struggle to implement strategies, emphasizing the urgent need for education, collaboration and tools to align practices with guidelines on non-malignant pain and opioids.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Coded diagnoses from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in research.

AIMS: To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45-65 years at baseline, included between 2008-2012. Data from electronic health records were collected between 2012-2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM. RESULTS: After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92). CONCLUSIONS: ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.

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

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 (RR(adj): 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.

High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients.

To estimate the risk of venous thrombosis associated with pancreatic malignancies we followed a cohort of patients with pancreatic cancer (n = 202). We calculated incidence rates of venous thrombosis and compared this with population rates using a Standardised Morbidity Ratio (SMR). The effects of location, histology and treatment were assessed by Cox-modelling. The incidence of venous thrombosis was 108.3/1000 patient-years (95% confidence interval (CI) 64.4-163.8), 58.6-fold increased (SMR 58.6, 95% CI 36.9-92.9). Patients with a tumour of the corpus/cauda had a 2-fold increased risk compared with those with a tumour of the caput. Patients treated with chemotherapy had a 4.8-fold increased risk (HR(adj) 4.8, 95% CI 1.1-20.8), whereas radiotherapy did not increase the risk. In a postoperative period of 30 d, patients had a 4.5-fold increased risk of venous thrombosis (HR(adj) 4.5, 95% CI 0.5-40.9). The risk was 1.9-fold increased in the presence of distant metastases (HR(adj) 1.9, 95% CI 0.7-5.1). Anti-thrombotic prophylaxis seems warranted in the first month after surgery, during and after treatment with chemotherapy, and when distant metastases have been diagnosed.

Old and new risk factors for upper extremity deep venous thrombosis.

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

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) occurred. 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.

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

BACKGROUND: Venous thrombosis is common in the older population. Assessment of risk factors is necessary to implement preventive measures. OBJECTIVES: We studied the associations between immobility-related risk factors and thrombosis, specifically, hospitalization, surgery, fractures, plaster cast use, minor injuries, and transient immobility at home, in an older population. PATIENTS AND METHODS: Analyses were performed in the Age and Thrombosis, Acquired and Genetic risk factors in the Elderly (AT-AGE) study, a two-center population-based case-control study. Consecutive cases aged > 70 years with a first-time thrombosis (n = 401) and control subjects > 70 years old without a history of thrombosis (n = 431) were included. Exclusion criteria were active malignancy and severe cognitive disorders. We calculated odds ratios (OR) with 95% confidence intervals (95% CI) after adjustment for age, sex, body mass index, study center, and population-attributable risks. RESULTS: There was a 15-fold (OR 14.8, 95% CI 4.4-50.4) increased risk of thrombosis within 2 weeks after hospital discharge. Surgery (OR 6.6, 95% CI 3.7-11.6), fractures (OR 12.7, 95% CI 3.7-43.7), plaster cast (OR 6.2, 95% CI 2.0-18.9), minor leg injuries (OR 1.9, 95% CI 1.1-3.3), and transient immobility at home (OR 5.0, 95% CI 2.3-11.2) were all associated with thrombosis risk over 3 months. The population-attributable risks for in-hospital immobility was 27%, and for out-of-hospital immobility, 15%. CONCLUSIONS: In those > 70 years of age, in-hospital and out-of hospital immobility are strong risk factors for thrombosis. Additional studies on preventive measures during immobilization in this age group should not focus solely on hospital settings.

Prognostic value of pro-adrenomedullin, procalcitonin and C-reactive protein in predicting outcome of febrile urinary tract infection.

Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker-plasma midregional pro-adrenomedullin (MR-proADM)-was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.

Changing prediction of mortality by systolic blood pressure with increasing age: the Rotterdam study.

There are indications that in persons of older age, systolic blood pressure (SBP) is no longer associated with mortality. This raises the question whether the predictive value of SBP changes from younger to older age groups. Analysis in the Rotterdam Study, a population-based prospective cohort study among 4,612 participants aged ≥55 years without previous cardiovascular disease and with a median follow-up of 14.9 (interquartile range, 11.1-15.8) years. Within four age groups (55-64, 65-74, 75-84, ≥85 years), the predictive value of baseline SBP for mortality was studied. From age 55 to ≥85 years, risk of all-cause mortality associated with SBP ≥160 mmHg decreased from HR 1.7 (95%CI 1.2-2.2) to HR 0.7 (95%CI 0.4-1.1), p for trend <0.001. For participants with SBP 140-159 mmHg, the risk decreased from HR 1.2 (95%CI 0.9-1.5) to HR 0.7 (95%CI 0.5-1.1), p for trend <0.001. Analyses in the 5-year age groups showed an increased risk with higher SBPs up to age 75 years. After 75 years, a trend towards SBP no longer being associated with an increased mortality risk was seen in our study. These findings need to be considered with recently reported beneficial effects of antihypertensive treatment in this age group.

Diabetic retinopathy screening in patients with diabetes mellitus in primary care: Incentives and barriers to screening attendance.

AIM: Although diabetic retinopathy (DR) screening is a basic component of diabetes care, uptake of screening programs is less than optimal. Because attendance rates and reasons for non-attendance in an unselected diabetes population are unknown, this study examines incentives and barriers to attend DR-screening. METHOD: Four focus groups provided patient-related themes concerning individual decision-making regarding attendance at DR-screening. A questionnaire measuring attendance rates and the influence of several factors was sent to 3236 diabetes patients (>18 years) in 20 Dutch general practices, of which 2363 (73%) responded. RESULTS: In the past 3 years, 81% of the patients had attended DR-screening. Patients not attending had lower levels of education, a more recent diagnosis of diabetes, and less frequently used insulin. There was no difference in DM types 1 and 2 patients regarding attendance. Patients attending more often visited health-care providers. Patients reported 'knowledge of detrimental effects of DR on visual acuity', 'sense of duty' and 'fear of impaired vision' as main incentives. The main barrier was the absence of a recommendation by the health-care provider. CONCLUSION: Knowledge about detrimental effects of DR on visual acuity and recommendation by health-care providers are important, possibly modifiable, factors in the attendance to DR screening.

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 patient's 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.