The ESSAG-trial protocol: A randomized controlled trial evaluating the efficacy of offering a self-sampling kit by the GP to reach women underscreened in the routine cervical cancer screening program.

BACKGROUND: In Flanders (Belgium), women not screened for cervical cancer (CC) within the last three years receive an invitation letter from the regional screening organization, the Centre for Cancer Detection (CCD), encouraging them to have a cervical specimen taken by their general practitioner (GP) or gynecologist. However, the coverage for CC screening remains suboptimal (63%). The offer of a self-sampling kit (SSK, for HPV testing) by a GP may trigger participation among women who do not attend regular screening. METHODS: The ESSAG-trial is a cluster-randomized controlled trial with three arms, each including 1125 women aged 31-64 years, who were not screened for CC in the last 6 years. In arm A, GPs offer a SSK when eligible women consult for any reason. In arm B, women receive a personal GP signed invitation letter including an SSK at their home address. In the control arm, women receive the standard invitation letter from the CCD. The primary outcome is the response rate at three months after inclusion. Secondary outcomes are: screen test positivity; compliance with foreseen follow-up among screen-positives; costs per invited and per screened women; as well as contrasts between trial arms and between socio-demographic categories. CONCLUSION: The ESSAG-trial will assess the effect of GP-based interventions using SSKs on CC screening participation among hard-to-reach populations. Findings will inform policymakers about feasible strategies on increasing CC screening that may be rolled-out throughout the whole region. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05656976.

Clinical audit of quality of care among patients with viral hepatitis in primary care in a low endemic region.

BACKGROUND: The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma. OBJECTIVES: This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level. METHODS: This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021. RESULTS: A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively. CONCLUSION: In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.

Infections with the hepatitis B virus (HBV) and hepatitis C virus (HCV) are a leading cause of death worldwide. Over the last decade, several new therapeutic agents have been developed and can now prevent hepatitis-related deaths. Awareness and increasing testing rates for viral hepatitis in primary care could therefore contribute to control these diseases. The findings of our clinical audit among primary health care practices in Flanders, Belgium demonstrate that screening for HBV and HCV infection can be improved in primary health care in a low endemic region, especially in high-risk groups (e.g. migrants who originate from an endemic country) and patients with abnormal ALT level. The observed suboptimal testing rate in primary health care may be due to a lack of information on risk groups. Future research should focus on interventions to enhance testing, linkage to care, and treatment initiation for HBV and HCV infection among well-defined risk groups in primary health care.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

A longitudinal transition imputation model for categorical data applied to a large registry dataset.

Imputation of longitudinal categorical covariates with several waves and many predictors is cumbersome in terms of implausible transitions, colinearity, and overfitting. We designed a simulation study with data obtained from a general practitioners' morbidity registry in Belgium for three waves, with smoking as the longitudinal covariate of interest. We set varying proportions of data on smoking to missing completely at random and missing not at random with proportions of missingness equal to 10%, 30%, 50%, and 70%. This study proposed a 3-stage approach that allows flexibility when imputing time-dependent categorical covariates. First, multiple imputation using fully conditional specification or multiple imputation for the predictor variables was deployed using the wide format such that previous and future information of the same patient was utilized. Second, a joint Markov transition model for initial, forward, backward, and intermittent probabilities was developed for each imputed dataset. Finally, this transition model was used for imputation. We compared the performance of this methodology with an analyses of the complete data and with listwise deletion in terms of bias and root mean square error. Next, we applied this methodology in a clinical case for years 2017 to 2021, where we estimated the effect of several covariates on the pneumococcal vaccination. This methodological framework ensures that the plausibility of transitions is preserved, overfitting and colinearity issues are resolved, and confounders can be utilized. Finally, a companion R package was developed to enable the replication and easy application of this methodology.

Predictors for unplanned hospital admissions in community dwelling adults: A dynamic cohort study.

BACKGROUND: Polypharmacy and inappropriate medication use are associated with unplanned hospital admissions. Targeted interventions might reduce the hospitalization risk. Yet, it remains unclear which patient profiles derive the largest benefit from such interventions. OBJECTIVE: The aim of this study was to determine independent risk factors, among which polypharmacy, for unplanned hospital admissions in a cohort of community dwelling adults. METHODS: A retrospective study was performed using a large general practice registry and an insurance database in Flanders, Belgium. Community dwelling adults aged 40 years or older with data for 2013-2015 were included. The index date was the last general practitioner contact in 2014. Determinants were collected during the preceding year. Unplanned hospital admissions were determined during the year after the index date. Univariable logistic regression models were fitted on each risk factor for an unplanned hospital admission as the primary outcome. Two multivariable models were derived. RESULTS: In total, 40411 patients were included and 2126 (5.26%) experienced an unplanned hospital admission. Mean age was 58.3 (±12.3) years. The two models identified the following determinants for an unplanned hospital admission: excessive polypharmacy, older age, male sex, number of comorbidities, atrial fibrillation, chronic obstructive pulmonary disease or stroke, low hemoglobin, use of hypnotics, antipsychotics, antidepressants or antiepileptics and prior hospital and general practitioner visits. Prior hospital visits was the largest determinant. CONCLUSIONS: In our study we identified and confirmed the presence of known determinants for unplanned hospital admissions in community dwelling adults, most of which align with a geriatric phenotype. Our findings can inform the allocation of interventions aiming to reduce unplanned hospital admissions.

Trends in the registration of anxiety in Belgian primary care from 2000 to 2021: a registry-based study.

BACKGROUND: Anxiety is frequently encountered in general practice, but figures regarding prevalence and incidence in this healthcare setting remain scarce. AIM: To provide insight about the trends in prevalence and incidence of anxiety in Belgian general practice, as well as the comorbidities and treatment of anxiety in this context. DESIGN AND SETTING: Retrospective cohort study using the INTEGO morbidity registration network, with clinical data from over 600 000 patients in Flanders, Belgium. METHOD: Trends in age-standardised prevalence and incidence of anxiety from 2000 to 2021 as well as prescriptions in patients with prevalent anxiety were analysed with joinpoint regression. Comorbidity profiles were analysed using the Cochran-Armitage test and the Jonckheere-Terpstra test. RESULTS: During the 22-year study period, 8451 unique patients with anxiety were identified. The prevalence of anxiety diagnoses rose significantly during this period, from 1.1% in 2000 to 4.8% in 2021. The overall incidence rate rose from 1.1/1000 patient-years (PY) in 2000 to 9.9/1000 PY in 2021. The average chronic disease count per patient increased significantly during the study period, from 1.5 to 2.3 chronic conditions. The most frequent comorbidities in patients with anxiety in 2017-2021 were malignancy (20.1%), hypertension (18.2%), and irritable bowel syndrome (13.5%). The proportion of patients treated with psychoactive medication rose from 25.7% to almost 40% over the study period. CONCLUSION: A significantly increasing prevalence and incidence of physician-registered anxiety was found in the study. Patients with anxiety tend to become more complex, with more comorbidities. Treatment for anxiety in Belgian primary care is very dependent on medication.

Incidence rates and trends of childhood urinary tract infections and antibiotic prescribing: registry-based study in general practices (2000 to 2020).

BACKGROUND: To improve the management of childhood urinary tract infections, it is essential to understand the incidence rates, testing and treatment strategy. METHODS: A retrospective study using data from 45 to 104 general practices (2000 to 2020) in Flanders (Belgium). We calculated the incidence rates (per 1000 person-years) of cystitis, pyelonephritis, and lab-based urine tests per age (< 2, 2-4, 5-9 and 10-18 years)) and gender in children and performed an autoregressive time-series analysis and seasonality analysis. In children with UTI, we calculated the number of lab-based urine tests and antibiotic prescriptions per person-year and performed an autoregressive time-series analysis. RESULTS: There was a statistically significant increase in the number of UTI episodes from 2000 to 2020 in each age group (p < 0.05), except in boys 2-4 years. Overall, the change in incidence rate was low. In 2020, the incidence rates of cystitis were highest in girls 2-4 years old (40.3 /1000 person-years 95%CI 34.5-46.7) and lowest in boys 10-18 (2.6 /1000 person-years 95%CI 1.8-3.6) The incidence rates of pyelonephritis were highest in girls 2-4 years (5.5, 95%CI 3.5-8.1 /1000 person-years) and children < 2 years of age (boys: 5.4, 95%CI 3.1-8.8 and girls: 4.9, 95%CI 2.7-8.8 /1000 person-years). In children 2-10 years, there was an increase in number of lab-based urine tests per cystitis episode per year and a decrease in total number of electronic antibiotic prescriptions per cystitis episode per year, from 2000 to 2020. In children with cystitis < 10 years in 2020, 51% (95%CI 47-56%) received an electronic antibiotic prescription, of which the majority were broad-spectrum agents. CONCLUSIONS: Over the last 21 years, there was a slight increase in the number of UTI episodes diagnosed in children in Flemish general practices, although the overall change was low. More targeted antibiotic therapy for cystitis in accordance with clinical guidelines is necessary to reduce the use of broad-spectrum agents in children below 10 years.

Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study.

AIMS: This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update "Management of Hyperglycemia in Type 2 Diabetes" recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin. METHODS: Data were obtained in 2015 from Intego, a morbidity registration network of 111 general practitioners (GPs) working in 48 practices and including 123 261 registered patients. RESULTS: Of 123 261 patients, 9616 had T2D. Of these patients, 4200 (43.7%) presented with ASCVD and/or CKD and/or HF. Specifically, 3348 (34.8%) patients had ASCVD, 388 (4.0%) had heart failure, and 1402 (14.6%) had CKD. Compared to patients without any of these comorbidities, patients with at least 1 of these conditions were older (69.7 ±12.6 vs. 63.1±12.5 years), had higher LDL-C values (104.2±35.8 mg/dl vs. 97.2±37.7) and less frequently achieved the systolic blood pressure target of 140 mm Hg (53 vs. 61%) (all p<0.001). Comorbid patients also had significantly more other comorbidities, such as dementia or cancer; received more recommended medications, such as statins; and received less metformin. Most patients with HF (325; 3.4%) had ASCVD (114; 1.2%), CKD (76; 0.8%), or both (135; 1.4%). In total, 478 patients with CKD (5.0%) also had ASCVD. CONCLUSIONS: At the primary care level, 44% of T2D patients suffer from ASCVD, CKD, and/or HF, and thus qualify for GLP-1RA or SGLT2-I therapy.

Use of antibiotics and colorectal cancer risk: a primary care nested case-control study in Belgium.

OBJECTIVES: To examine the association between the use of oral antibiotics and subsequent colorectal cancer risk. DESIGN: Matched case-control study. SETTING: General practice centres participating in the Integrated Computerised Network database in Flanders, Belgium. PARTICIPANTS: In total, 1705 cases of colorectal cancer diagnosed between 01 January 2010 and 31 December 2015 were matched to 6749 controls by age, sex, comorbidity and general practice centre. PRIMARY OUTCOME MEASURE: The association between the number of prescriptions for oral antibiotics and the incidence of colorectal cancer over a period of 1-10 years, estimated by a conditional logistic regression model. RESULTS: A significantly increased risk of colorectal cancer (OR 1.25, 95% CI 1.10 to 1.44) was found in subjects with one or more prescriptions compared with those with none after correction for diabetes mellitus. No dose-response relationship was found. CONCLUSIONS: This study resulted in a modestly higher risk of having colorectal cancer diagnosed after antibiotic exposure. The main limitation was missing data on known risk factors, in particular smoking behaviour. This study did not allow us to examine the causality of the relationship, indicating the need of further investigation.

The effect of a case-finding app on the detection rate of atrial fibrillation compared with opportunistic screening in primary care patients: protocol for a cluster randomized trial.

BACKGROUND: Atrial fibrillation is a cardiac arrhythmia commonly encountered in a primary care setting. Current screening is limited to pulse palpation and ECG confirmation when an irregular pulse is found. Paroxysmal atrial fibrillation will, however, still be difficult to pick up. With the advent of smartphones, screening could be more cost-efficient by making use of simple applications, lowering the need for intensive screening to discover (paroxysmal) atrial fibrillation. METHODS/DESIGN: This cluster randomized trial will examine the effect of using a smartphone-based application such as FibriCheck® on the detection rate of atrial fibrillation in a Flemish general practice population. This study will be conducted in 22 primary care practices across the Flanders region of Belgium and will last 12 months. Patients above 65 years of age will be divided in control and intervention groups on the practice level. The control group will be subjected to standard opportunistic screening only, while the intervention group will be prescribed the FibriCheck® app on top of this opportunistic screening. The difference in detection rate between control and intervention groups will be calculated at the end of the study. We will use the online platform INTEGO for pseudonymized data collection and analysis, and risk calculation. DISCUSSION: Smartphone applications might offer a way to cost-effectively screen for (paroxysmal) atrial fibrillation in a primary care setting. This could open the door for the update of future screening guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT04545723 . Registered on September 10, 2020.

Comorbidity burden in the first three years after diagnosis in patients with rheumatoid arthritis, psoriatic arthritis or spondyloarthritis: a general practice registry-based study.

OBJECTIVES: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) are chronic inflammatory rheumatic conditions with high levels of comorbidity requiring additional therapeutic attention. We aimed to compare the 3-year comorbidity incidence and pain medication prescription in patients diagnosed with RA, PsA or SpA versus controls. METHODS: Data between 1999 and 2012 were obtained from Intego, a general practitioner (GP) morbidity registry in Flanders, Belgium. Cases were identified by International Classification of Primary Care (ICPC-2) codes representing 'rheumatoid/seropositive arthritis (L88)' or 'musculoskeletal disease other (L99)'. The registered keywords mapped to these ICPC-2 codes were further verified and mapped to a RA/SpA/PsA diagnosis. Controls were matched on age, gender, GP practice and diagnosis date. We analysed the 3-year comorbidity burden in cases and controls, measured by the Rheumatic Diseases Comorbidity Index (RDCI). All electronically GP-prescribed drugs were registered. RESULTS: In total, 738, 229 and 167 patients were included with a diagnosis of RA, SpA or PsA, respectively. Patients with RA or PsA had comparable median RDCI scores at baseline, but higher scores at year 3 compared with controls (RA: p=0.010; PsA: p=0.008). At baseline, depression was more prevalent in PsA patients vs controls (p<0.003). RA patients had a higher 3-year incidence of cardiovascular disease including myocardial infarction than controls (p<0.035). All disease population were given more prescriptions than controls for any pain medication type, even opioids excluding tramadol. CONCLUSIONS: This study highlights the increasing comorbidity burden of patients with chronic inflammatory rheumatic conditions, especially for individuals with RA or PsA. The high opioid use in all populations was remarkable.

Fast and optimal algorithm for case-control matching using registry data: application on the antibiotics use of colorectal cancer patients.

BACKGROUND: In case-control studies most algorithms allow the controls to be sampled several times, which is not always optimal. If many controls are available and adjustment for several covariates is necessary, matching without replacement might increase statistical efficiency. Comparing similar units when having observational data is of utter importance, since confounding and selection bias is present. The aim was twofold, firstly to create a method that accommodates the option that a control is not resampled, and second, to display several scenarios that identify changes of Odds Ratios (ORs) while increasing the balance of the matched sample. METHODS: The algorithm was derived in an iterative way starting from the pre-processing steps to derive the data until its application in a study to investigate the risk of antibiotics on colorectal cancer in the INTEGO registry (Flanders, Belgium). Different scenarios were developed to investigate the fluctuation of ORs using the combination of exact and varying variables with or without replacement of controls. To achieve balance in the population, we introduced the Comorbidity Index (CI) variable, which is the sum of chronic diseases as a means to have comparable units for drawing valid associations. RESULTS: This algorithm is fast and optimal. We simulated data and demonstrated that the run-time of matching even with millions of patients is minimal. Optimal, since the closest controls is always captured (using the appropriate ordering and by creating some auxiliary variables), and in the scenario that a case has only one control, we assure that this control will be matched to this case, thus maximizing the cases to be used in the analysis. In total, 72 different scenarios were displayed indicating the fluctuation of ORs, and revealing patterns, especially a drop when balancing the population. CONCLUSIONS: We created an optimal and computationally efficient algorithm to derive a matched case-control sample with and without replacement of controls. The code and the functions are publicly available as an open source in an R package. Finally, we emphasize the importance of displaying several scenarios and assess the difference of ORs while using an index to balance population in observational data.

Polypharmacy and excessive polypharmacy in community-dwelling middle aged and aged adults between 2011 and 2015.

AIMS: We aimed to assess the prevalence, components and evolution of polypharmacy and to evaluate risk factors associated with polypharmacy. METHODS: A retrospective dynamic cohort study was performed, using a primary healthcare database comprising Flemish community-dwelling adults aged ≥40 years between 2011 and 2015. Polypharmacy and excessive polypharmacy were defined as the use of 5-9 or minimum 10 different medications during 1 year, respectively. Temporal changes were analysed using an autoregressive error model. Risk factors for polypharmacy were evaluated using logistic regression. RESULTS: In total, 68 426 patients were included in the analysis. The prevalence of polypharmacy was 29.5% and 16.1% for excessive polypharmacy in 2015. The age-standardised prevalence rate of patients using minimum five medications increased with 1.3% per year (95% confidence interval (CI): 0.1968-2.4279). The mean number of unplanned hospital admissions was 0.07 (standard deviation (SD) 0.33) for polypharmacy patients and 0.19 (SD 0.53) for excessive polypharmacy patients. Four risk factors were found to be significantly correlated with polypharmacy: age (odds ratio (OR) 1.015; 95% CI: 1.013-1.017), female gender (OR 1.161; 95% CI: 1.108-1.216), number of chronic diseases (OR 1.126; 95% CI: 1.114-1.139) and number of general practitioner contacts (OR 1.283; 95% CI: 1.274-1.292). CONCLUSION: The prevalence of polypharmacy increased between 2011 and 2015. Polypharmacy and excessive polypharmacy patients appeared to differ based on our observations of characteristics, drug therapy and outcomes. Age, female gender, number of chronic diseases and number of general practitioner contacts were associated with polypharmacy.

Burden of infections on older patients presenting to general practice: a registry-based study.

BACKGROUND: Estimates on the incidence rates of infections are needed to assess the burden of disease in the community. OBJECTIVE: To assess incidence rates of potentially serious infections in patients aged 65 years and over presenting to Flemish general practice from 2000 to 2015, and to describe patient characteristics. METHODS: We performed a retrospective study, based on data provided by the Intego morbidity registry of the KU Leuven, which includes the electronic medical records of 111 general practitioners. Incidence rates were calculated taking person-time at risk into account, and longitudinal trends from 2000 to 2015 were analysed using autoregressive time-series analyses. RESULTS: On average, a person aged 65 years or older has an 8.0% risk of getting a potentially serious infection each year. Acute cystitis was the most often occurring potentially serious infection [39.8/1000 person-years; 95% confidence interval (CI): 39.4-40.2], followed by influenza like illness (ILI, 24.3/1000 person-years; 95% CI: 24.0-24.6) and pneumonia (9.7/1000 person-years; 95% CI: 9.5-9.9). The incidence rates of pneumonia were higher in older age groups and in men, whereas they were markedly lower for ILI at older ages, in both genders. From 2000 to 2015, overall incidence rates decreased significantly for ILI, while they increased in women for pneumonia, acute cystitis and pyelonephritis. Common chronic comorbidities were non-insulin dependent diabetes, chronic obstructive pulmonary disease, asthma, heart failure and chronic renal insufficiency. CONCLUSIONS: Potentially serious infections are quite common in an older patient population presenting to primary care. They are accompanied by several chronic comorbidities, which may differ by infection type.

Trends in multimorbidity and polypharmacy in the Flemish-Belgian population between 2000 and 2015.

OBJECTIVES: The aim of this paper was to describe the time trends in the prevalence of multimorbidity and polypharmacy in Flanders (Belgium) between 2000 and 2015, while controlling for age and sex. METHODS: Data were available from Intego, a Flemish-Belgian general practice-based morbidity registration network. The practice population between 2000 and 2015 was used as the denominator, representing a mean of 159,946 people per year. Age and gender-standardised prevalence rates were used for the trends of multimorbidity and polypharmacy in the total population and for subgroups. Joinpoint regression analyses were used to analyse the time trends and breaks in trends, for the entire population as well as for specific age and sex groups. RESULTS: Overall, in 2015, 22.7% of the population had multimorbidity, while the overall prevalence of polypharmacy was 20%. Throughout the study period the standardised prevalence rate of multimorbidity rose for both sexes and in all age groups. The largest relative increase in multimorbidity was observed in the younger age groups (up to the age of 50 years). The prevalence of polypharmacy showed a significant increase between 2000 and 2015 for all age groups except the youngest (0-25 years). CONCLUSION: For all adult age groups multimorbidity and polypharmacy are frequent, dynamic over time and increasing. This asks for both epidemiological and interventional studies to improve the management of the resulting complex care.

Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries.

BACKGROUND: Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients. OBJECTIVE: To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients. DESIGN: We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment. MAIN MEASURES: Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (ORadj) were calculated for GPs' advice to stop. KEY RESULTS: Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99). CONCLUSIONS: The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.

Factors associated with Prolonged Inaction in the hypoglycaemic treatment in people with non-insulin dependent Type 2 Diabetes and elevated glycated haemoglobin: A registry-based cohort study.

AIMS: To assess factors associated with Prolonged Inaction (PI) in insulin-naïve patients with Type 2 Diabetes Mellitus (T2DM). PI was defined as the absence of treatment initiation or intensification for ≥12 months despite HbA1c >7% (53mmol/mol). METHODS: A retrospective cohort study was conducted based on data from Intego, a Flemish General Practice registry. The study period ranged from January 1, 2006 to December 31, 2013. Patients with insulin therapy before the start of the study period were excluded from the analysis. A mixed effects logistic regression was used to assess the association of PI with the presence of co-morbidities, co-medications, process parameters and bio-clinical parameters. RESULTS: In a population of 2265 patients with T2DM, 578 insulin-naive patients presented with an HbA1c >7% (53mmol/mol) for ≥12 months. Median follow-up was 1.2 years, median age 67 years, 55% were male. PI was present in 340 patients (59%) and associated with moderate to severe Chronic Kidney Disease, absence of a mental health disorder, less frequent HbA1c measurements, lower HbA1c values and a smaller number of co-medications. CONCLUSIONS: PI is highly prevalent in primary care, particularly in patients with less complex disease status and with less intensive follow-up.

Correlates of dyspnoea and its association with adverse outcomes in a cohort of adults aged 80 and over.

Background: adults aged 80 and over, a fast growing age-group, with increased co-morbidity and frailty have not been the focus of previous research on dyspnoea. We investigate the correlates of dyspnoea and its association with adverse outcomes in a cohort of adults aged 80 and over. Methods: about 565 community-dwelling adults aged 80 and over of the BELFRAIL prospective cohort had assessment of Medical Research Council dyspnoea scale (MRC), forced expiratory volume in 1 s (FEV1), N-terminal pro-brain natriuretic peptide (NT-proBNP), physical performance tests, grip strength, 15 items geriatric depression scale, activities of daily living (ADL), body mass index (BMI) and demographics data. Kaplan-Meier survival curves, Cox and logistic multivariable regression, classification and regression tree (CART) analysis assessed association of dyspnoea (MRC 3-5) with time-to-cardiovascular and all-cause death (5 years), time to first hospitalisation (3 years), new/worsened ADL disability (2 years), and its correlates. Results: participants with dyspnoea MRC 3-5 (29.9%) had increased hazard ratios for cardiovascular mortality 2.85 (95% confidence interval 1.93-4.20), all-cause mortality 2.04 (1.58-2.64), first hospitalisation 1.72 (1.35-2.19); and increased odds ratio for new/worsened disability 2.49 (1.54-4.04), independent of age, sex and smoking status. Only FEV1, physical performance, BMI and NT-proBNP (in order of importance) were selected in the tree-based classification model for dyspnoea. Conclusions: in a cohort of adults aged 80 and over, dyspnoea was common and an independent predictor of adverse outcomes, with cardio-respiratory and physical performance impairments as key independent correlates. Its routine and comprehensive evaluation in primary care could be very valuable in caring for this age-group.

Too many, too few, or too unsafe? Impact of inappropriate prescribing on mortality, and hospitalization in a cohort of community-dwelling oldest old.

AIMS: Little is known about the impact of inappropriate prescribing (IP) in community-dwelling adults, aged 80 years and older. The prevalence at baseline (November 2008September 2009) and impact of IP (misuse and underuse) after 18 months on mortality and hospitalization in a cohort of community-dwelling adults, aged 80 years and older (n = 503) was studied. METHODS: Screening Tool of Older People's Prescriptions (STOPP-2, misuse) and Screening Tool to Alert to Right Treatment (START-2, underuse) criteria were cross-referenced and linked to the medication use (in Anatomical Therapeutic Chemical coding) and clinical problems. Survival analysis until death or first hospitalization was performed at 18 months after inclusion using Kaplan-Meier, with Cox regression to control for covariates. RESULTS: Mean age was 84.4 (range 80-102) years. Mean number of medications prescribed was 5 (range 0-16). Polypharmacy (≥5 medications, 58%), underuse (67%) and misuse (56%) were high. Underuse and misuse coexisted in 40% and were absent in 17% of the population. A higher number of prescribed medications was correlated with more misused medications (rs  = .51, P < 0.001) and underused medications (rs  = .26, P < 0.001). Mortality and hospitalization rate were 8.9%, and 31.0%, respectively. After adjustment for number of medications and misused medications, there was an increased risk of mortality (HR 1.39, 95% CI 1.10, 1.76) and hospitalization (HR 1.26, 95% CI 1.10, 1.45) for every additional underused medication. Associations with misuse were less clear. CONCLUSION: IP (polypharmacy, underuse and misuse) was highly prevalent in adults, aged 80 years and older. Surprisingly, underuse and not misuse had strong associations with mortality and hospitalization.

Polypharmacy in a Belgian cohort of community-dwelling oldest old (80+).

OBJECTIVES: Polypharmacy is highly prevalent among older people (65+), but little is known on the medication use of the oldest old (80+). This study explores the medication use of the Belgian community-dwelling oldest old in relation to their demographic, clinical and functional characteristics. METHODS: Baseline data was used from the BELFRAIL study; a prospective, observational population-based cohort of Belgian community-dwelling patients (80+). General practitioners recorded clinical problems and medications. Medications were coded by the Anatomic Therapeutic Chemical classification. RESULTS: Participants' (n = 503) mean age was 84.4 years (range 80-102) and 61.2% was female. Median chronic medication use was 5 (range 0-16). Polypharmacy (≥5 medications) was high (57.7%), with excessive polypharmacy (≥10 medications) in 9.1%. Most commonly used medication group were antithrombotics, but also benzodiazepines and antidepressants were frequently consumed. Demographics related to polypharmacy (univariate analysis) were female gender, low education and moderate alcohol use. Age, care dependency and cognitive impairment showed no association with polypharmacy. In multivariate analysis, the predominant association with polypharmacy was found for multimorbidity (OR 1.78, 95% CI 1.5-2.1), followed by depression (OR 3.7, 95% CI 4.4-9.7) and physical activity (OR 0.8, 95% CI 0.7-0.9). CONCLUSIONS: Polypharmacy was high among Belgian community-dwelling oldest old (80+). Determinants of polypharmacy were interrelated, but dominated by multimorbidity. On top of the burden of multimorbidity, polypharmacy was independently associated with less physical activity, and with depressive symptoms.