Multimorbidity and chronic co-prescription networks and potential interactions in adult patients with epilepsy: MorbiNet study.

OBJECTIVE: We constructed epilepsy multimorbidity networks to study associations with chronic conditions, and co-prescriptions and drug-disease networks to assess potential interactions. We conducted a population-based study in Catalonia, Spain, with electronic files of 3,135,948 adult patients with multimorbidity, 32,625 of them with epilepsy (active diagnosis any time during 2006-2017). We constructed epilepsy comorbidity networks using logistic regression models from odds ratio estimates adjusted by age, sex, and comorbidities with R software and generated trajectories to study the progression of epilepsy. We constructed drug-disease and co-prescription networks using mixed models with repeated measures adjusting by age, sex, and period with chronic prescription invoiced data. Comorbidity more frequently preceding epilepsy included cerebrovascular accident (OR: 3.59), congenital anomalies (2.18), and multiple sclerosis (1.33); and following epilepsy: dementia (1.91), personality disorder (1.59), alcohol abuse (1.22), and Parkinson (1.21). Mental retardation (13.08), neurological cancer (8.49), benign neoplasm (4.69), infections (3.14), and psychosis (1.58) might precede or not epilepsy. A common progression was to schizophrenia, dementia, and other neurological diseases (mainly cerebral palsy and other degenerative diseases of nervous system). Co-prescription associations with major-moderate potential interactions were 54% for carbamazepine, 61% phenytoin, 53% phenobarbital, and 32% valproate. Major potential interactions were with antipsychotic, anxiolytic, opioid, cardiovascular, and other anti-seizure medications (ASMs). The most frequent comorbidities of epilepsy were congenital, cerebrovascular, and neurological and psychiatric conditions. High comorbidity and co-prescription with potential interactions can increase the complexity of care of patients with epilepsy.

[Update on the use of insulins for the primary care physician]. / Actualización en el uso de insulinas para el médico de familia.

Insulin treatment in type 2 diabetes mellitus patients is still essential and its usage has increased during recent years. Despite this, the level of control continues to be very poor. Insulin treatment is initiated with control levels above the recommendations set by the Clinical Practice Guidelines (CPG) and patients are exposed to very high blood glucose levels during long periods of time. This paper reviews the role of insulin in the different CPG, the criteria for therapy initiation and intensification, the beginning of the intensification and the different types of insulin which are commercialized in our country. Moreover, we discuss insulinization in special situations such as corticosteroid treatment, fragile elderly patients, palliative care situations, chronic kidney disease or during Ramadan. Finally, the problem of therapeutic inertia in insulinization is also addressed.

Adherence, control of cardiometabolic factors and therapeutic inertia in patients with type 2 diabetes in the primary care setting.

INTRODUCTION: Studies on treatment adherence to glucose-lowering drugs among patients with type 2 diabetes (T2D) including concomitant treatment for other cardiovascular risk factors are scarce. We aimed to estimate the prevalence of good adherence to all medications used to control diabetes, hypertension and dyslipidemia and to analyse cardiometabolic control and its associated factors in T2D patients in the primary care (PC) setting. METHODS: Observational, retrospective study conducted in adult patients with T2D who were followed in the PC setting in Spain. Patients were classified as adherent in a particular category if the summary of the proportion of days covered (PDC) for a particular medication category was ≥80% and were considered globally adherent if the PDC was ≥80% for each of the 3 medication categories. RESULTS: A total of 457 evaluable patients were recruited, among which 321 patients (70.3%, 95% CI 65.8 to 74.4) were adherent to the three drug categories. The proportion of patients controlled for the 3 cardiometabolic risk factors was 31% according to the contemporary clinical practice guideline criteria, 58% according to investigator judgment and 36% when the objective for HbA1c was individualized. In a multivariate analysis, presenting comorbidities was associated with a lower likelihood of showing adequate control of dyslipidemia (odds ratio [OR] 0.25, 95% CI, 0.16-0.40) and the three cardiometabolic factors as a whole (OR 0.43, 95% CI 0.26-0.70). In a post hoc analysis, therapeutic inertia was found to be greater for dyslipidemia and hypertension than for T2D. CONCLUSIONS: Despite a relatively high adherence to all medications for treating diabetes, hypertension and dyslipidemia in patients with T2D in the PC setting in Spain, the control of cardiometabolic risk factors as a whole is far from optimal. This could be related, at least in part, to the high frequency of comorbidity of these patients.

Experience of Patients with Diabetes and Other Cardiovascular Risk Factors with Health Professionals and Healthcare in Spain.

We aimed to evaluate the experience of patients with type 2 diabetes (T2DM) with healthcare received in Spain. This was a retrospective, observational study in patients with T2DM cared for in primary healthcare (PHC) centers. A cross-sectional analysis of the patients' experience data was performed using the Instrument for the Evaluation of the Experience of Chronic Patients (IEXPAC). A total of 475 patients with T2DM were recruited from 36 PHC centers, of which 248 (52.2%) completed the IEXPAC questionnaire. The IEXPAC total mean score (range 0-10) was 7 points, with an average "new relational model" score of 2.5 points. The mean continuity of care score after hospital discharge was 6.2 points. The results showed that 8% of the patients always or almost always used the internet to check their medical history, appointments or other data from their healthcare service, and 15% responded that healthcare professionals always or almost always informed them of forums or other reliable internet sites to obtain information about their illness. The study results show that there is a wide margin for improvement in the experience of patients with T2DM with healthcare in Spain, especially regarding the information patients receive or can obtain.

MorbiNet Study: Hypothyroidism Comorbidity Networks in the Adult General Population.

PURPOSE: Multimorbidity impacts quality of life. We constructed hypothyroidism comorbidity networks to identify positive and negative associations with other prevalent diseases. METHODS: We analyzed data of 285 342 patients with hypothyroidism from 3 135 948 adults with multimorbidity in a population-based study in Catalonia, Spain, (period: 2006-2017). We constructed hypothyroidism comorbidity networks using logistic regression models, adjusted by age and sex, and for men and women separately. We considered relevant associations those with odds ratios (OR) >1.2 or <0.8 and P value < 1e-5 to identify coexistence greater (or smaller) than the expected by the prevalence of diseases. Multivariate models considering comorbidities were used to further adjust OR values. RESULTS: The conditions associated included larynx cancer (adjusted OR: 2.48), congenital anomalies (2.26), thyroid cancer (2.13), hyperthyroidism (1.66), vitamin B12/folate deficiency anemia (1.57), and goiter (1.56). The network restricted to men had more connections (mental, cardiovascular, and neurological) and stronger associations with thyroid cancer (7.26 vs 2.55), congenital anomalies (5.11 vs 2.13), hyperthyroidism (4.46 vs 1.69), larynx cancer (3.55 vs 1.67), and goiter (3.94 vs 1.64). After adjustment for comorbidities, OR values were more similar in men and women. The strongest negative associations after adjusting for comorbidities were with HIV/AIDS (OR: 0.71) and tobacco abuse (0.77). CONCLUSIONS: Networks show direct and indirect hypothyroidism multimorbidity associations. The strongest connections were thyroid and larynx cancer, congenital anomalies, hyperthyroidism, anemia, and goiter. Negative associations included HIV/AIDS and tobacco abuse. The network restricted to men had more and stronger associations, but not after adjusting for comorbidities, suggesting important indirect interactions.

Resource use and costs in patients with poorly controlled type 2 diabetes mellitus and obesity in routine clinical practice in Spain.

OBJECTIVE: To compare healthcare resource use (HRU) and annual costs in type 2 diabetes mellitus (T2DM) patients with poor glycaemic control and obesity versus good glycaemic control without obesity. METHODS: Observational retrospective study based on the analysis of electronic medical records from the BIG-PAC database, with one year of follow-up. T2DM patients aged ≥30 years who requested medical care during 2013 were included. Annual HRU and costs per patient were compared between a reference group (HbA1c ≥ 8%, BMI ≥30 kg/m2, receiving ≥2 oral antidiabetic drugs [OADs]) and a control group (HbA1c < 7% and BMI <30 kg/m2). Direct and indirect costs (lost productivity) were analysed. Cost comparisons across groups were made using the analysis of covariance (ANCOVA) for each cost component, with age, sex, time from diagnosis, Charlson comorbidity index, OAD number and sex by group interaction as covariates. RESULTS: During the follow-up, patients in the reference group (N = 2709) had a greater HRU than those in the control group (N = 5266), especially in the number of primary care (PC) visits (11.8 vs. 9.8; 95%CI: 11.5-12.1 vs. 9.6-10.0) and days of hospitalization (1.1 vs 0.6; 95%CI: 1.0-1.2 vs. 0.5-0.7). The main components of the total cost were hospital admissions (24.5%), productivity losses (16.3%), complementary tests (14.4%), PC visits (14.2%) and medication (13.6%) in the reference group and medication (19.6%), hospital admissions (18.7%) and PC visits (18.2%) in the control group. The corrected mean annual cost per patient was higher in the reference than in the control group: €1804 vs. €1309; p < .001. CONCLUSIONS: Poor glycaemic control and obesity in T2DM patients were associated with increased HRU and costs in routine clinical practice.

MorbiNet: multimorbidity networks in adult general population. Analysis of type 2 diabetes mellitus comorbidity.

Multimorbidity has great impact on health care. We constructed multimorbidity networks in the general population, extracted subnets focused on common chronic conditions and analysed type 2 diabetes mellitus (T2DM) comorbidity network. We used electronic records from 3,135,948 adult people in Catalonia, Spain (539,909 with T2DM), with at least 2 coexistent chronic conditions within the study period (2006-2017). We constructed networks from odds-ratio estimates adjusted by age and sex and considered connections with OR > 1.2 and p-value < 1e-5. Directed networks and trajectories were derived from temporal associations. Interactive networks are freely available in a website with the option to customize characteristics and subnets. The more connected conditions in T2DM undirected network were: complicated hypertension and atherosclerosis/peripheral vascular disease (degree: 32), cholecystitis/cholelithiasis, retinopathy and peripheral neuritis/neuropathy (degree: 31). T2DM has moderate number of connections and centrality but is associated with conditions with high scores in the multimorbidity network (neuropathy, anaemia and digestive diseases), and severe conditions with poor prognosis. The strongest associations from T2DM directed networks were to retinopathy (OR: 23.8), glomerulonephritis/nephrosis (OR: 3.4), peripheral neuritis/neuropathy (OR: 2.7) and pancreas cancer (OR: 2.4). Temporal associations showed the relevance of retinopathy in the progression to complicated hypertension, cerebrovascular disease, ischemic heart disease and organ failure.

Clinical Inertia in Poorly Controlled Type 2 Diabetes Mellitus Patients with Obesity: An Observational Retrospective Study.

INTRODUCTION: To evaluate clinical inertia in patients with type 2 diabetes mellitus (T2DM), obesity and poor glycaemic control in routine clinical practice. METHODS: This was a retrospective, observational study based on the analysis of medical records from the BIG-PAC® database. Subjects who required medical care in 2013 with the following characteristics were enrolled in the study: age ≥ 30 years, diagnosis of T2DM, glycosylated haemoglobin (HbA1c) ≥ 8%, obesity (body mass index [BMI] ≥ 30 kg/m2) and treatment with ≥ 2 oral antidiabetic drugs (OADs). Inertia was evaluated by time (days) to the first intensification during the period while HbA1c levels were ≥ 8% and percentage of patients whose treatment was not intensified at 6 months, 1, 2 and 3 years and the end of follow-up. The minimum length of follow-up was 4 years. Descriptive analyses and Kaplan-Meier survival curves were performed. RESULTS: A total of 13,824 patients with T2DM receiving ≥ 2 OADs were identified; of these 2709 (19.6%) had HbA1c ≥ 8% and BMI ≥ 30 kg/m2, thus fulfilling the inclusion criteria. Of these 2709 patients, the mean age was 65.5 (standard deviation [SD] 12.0) years; 54.9% were male, mean HbA1c level was 9.2% (SD 1.3%); mean BMI was 32.1 (SD 0.9) kg/m2; and mean time from diagnosis was 8.2 (SD 3.0) years. HbA1c remained ≥ 8% for a median of 440 (95% confidence interval [CI] 421-459) days. The median time to first intensification was 456 (95% CI 429-483) days. No intensification had occurred in 77.8, 59.5, 41.5, 28.1 and 22.4% of patients at 6 months, 1, 2, 3 years and the end of follow-up, respectively. CONCLUSIONS: The patients with T2DM analysed in this study had a mean HbA1c of 9.2% at baseline, and this remained at ≥ 8% for > 1 year. The time to the first treatment intensification was longer than that recommended by guidelines. Treatment was not intensified in a large percentage of patients, with almost 60% of patients not receiving intensification at 1 year of follow-up.

Glycaemic control and treatment of type 2 diabetes in adults aged 75 years or older.

AIM: The aim of this study was to assess glycaemic control and prescribing practices of antihyperglycaemic treatment in patients with diabetes mellitus type 2 aged 75 years or older. METHODS: We analysed data from health electronic records from 4,581 persons attended at primary healthcare centres of the Institut Català de la Salut (ICS), in the Girona Sud area of Catalonia, Spain, during 2013 and 2016. Variables such as age, gender, body mass index (BMI), diabetes duration, age at diabetes diagnosis, glycated haemoglobin (HbA1c), creatinine, glomerular filtrate rate and the albumin/creatinine ratio in urine were collected. A descriptive analysis of the study variables was done to determinate the percentage of persons on antidiabetic treatment. RESULTS: We identified 4,421 persons aged 75 years or older who provided data on HbA1c and antidiabetic treatment. Mean age was 82.3 (5.1) years. In 58.1% of patients, the level of HbA1c was below 7.0%, while in 36.8% it was below 6.5%. Between patients with HbA1c below 7.0%, antidiabetic drugs were taken by 70.2%, where 15.2% were either on insulin, sulphonylureas or repaglinide therapy. CONCLUSION: Intensive treatment among older adults with diabetes mellitus type 2 is common in primary care clinical practice in our area. Intensive glycaemic control confers an increased risk of hypoglycaemia and little benefit among older individuals with diabetes. Physicians should take care more not to harm those populations and treatment should be de-intensified to reduce the risk of hypoglycaemia.

Therapeutic inertia in patients treated with two or more antidiabetics in primary care: Factors predicting intensification of treatment.

AIMS: To determine the patterns and predictors of treatment intensification in patients with type 2 diabetes on ≥2 non-insulin antidiabetic drugs (NIADs) and inadequate glycaemic control in primary care in Catalonia, Spain. MATERIAL AND METHODS: This was a retrospective analysis using electronic medical records from patients with HbA1c ≥ 7% and a first prescription for a new NIAD or insulin recorded from January 2010 to December 2014. Therapeutic inertia was defined as no intensification if HbA1c was ≥8% at baseline or during follow-up. Time to first intensification was evaluated by time-to-event analysis, and factors predicting intensification through a competing-risk regression model. RESULTS: Among 23 678 patients with HbA1c ≥ 7%, 26.2% were censored without treatment intensification after a median follow up of 4.2 years. Among the 12 730 patients in the subgroup with HbA1c ≥ 8% at baseline or during follow-up, therapeutic inertia was present in 18.1% of cases. In the overall cohort, mean HbA1c at initiation of insulin and NIAD were 9.4% ± 1.5% and 8.7% ± 1.3%, respectively. Median time to first intensification was 17.1 months in patients with HbA1c 8.0% to 9.9%, and 10.1 months in those with HbA1c > 10%. Variables strongly associated with intensification were HbA1c values 8.0% to 9.9% (subhazard ratio [SHR], 1.7; 95% CI, 1.65-1.78) and >10% (SHR, 2.5; 95% CI, 2.37-2.68); diabetes duration ≥20 years (SHR, 1.25; 95% CI, 1.11-1.41) and, to a lesser extent, female gender, presence of comorbidities, chronic kidney disease and microvascular complications. CONCLUSIONS: Intensification was not undertaken in 1 in 5 patients. Both HbA1c thresholds and time until therapy intensification exceeded current recommendations.

Concordance between two methods in measuring treatment adherence in patients with type 2 diabetes.

OBJECTIVE: We analyzed the concordance between two methods for measuring treatment adherence (TA) and studied the determinants of TA in patients with type 2 diabetes mellitus. METHODS: We conducted a cross-sectional descriptive study in a primary care center, involving 320 diabetic patients. TA was measured using the Haynes-Sackett (H-S) adherence test during the patient interview and based on pharmacy refill data. TA was calculated globally and by drug groups (antihypertensive, lipid-lowering, and antidiabetic drugs). RESULTS: Poor TA as measured by the H-S test was observed in 11.2% of the patients. Based on pharmacy refill data, there was a poor global TA rate of 30.3%, which was 33.3%, 26.6%, and 34.2% for oral antidiabetic, antihypertensive, and lipid-lowering drugs, respectively. Concordance between the two methods was poor. There was no relationship between the degree of disease control and TA as measured by the H-S test. Good TA measured based on pharmacy refill data for antidiabetic and antihypertensive drugs was associated with lower glycosylated hemoglobin and diastolic blood pressure values, respectively. Patients with good global TA showed lower glycosylated hemoglobin, diastolic blood pressure, and low-density lipoprotein cholesterol values. The multivariate analysis found good oral antidiabetic adherence to be associated to free pharmacy service; good antihypertensive drug adherence to the existence of comorbidities; and good lipid-lowering drug adherence to a history of ischemic heart disease, and a more experienced physician and/or female physician. CONCLUSION: Concordance between the two methods in assessing TA was low. Approximately one-third of the patients with type 2 diabetes mellitus presented poor TA in relation to antihypertensive, lipid-lowering, and antidiabetic medication. An improved TA was associated with a better control of the studied parameters. Comorbidities, such as ischemic heart disease and access to free pharmacy service, were identified as determinants of good TA.

Prevalence of depression in patients with type 2 diabetes attended in primary care in Spain.

OBJECTIVES: To estimate the prevalence of known and undiagnosed depression in patients with type 2 diabetes attended in primary care setting in Spain, and to determine the factors associated with the presence of depression. METHODS: This was a cross-sectional and multicenter study performed in a random sample of patients with type 2 diabetes attended in 21 primary care centers. Depressive symptoms were measured with the self-administered Patient Health Questionnaire (PHQ-9). RESULTS: A total of 411 patients were analyzed (mean age 70.8 (SD 10.3) years; 53.8% women). 29.2% of patients met the diagnostic criteria of depression, of whom 17% had known depression and 12.2% undiagnosed depression (PHQ-9 score ≥10, without a previous diagnosis of depression). Depression was more common in women (43.4%; 95% confidence interval [CI] 34.5-52.3%), widow (33.3%; 95% CI 27.9-38.7%), and hypothyroidism (12.5%; 95% CI 8.7-16.3%). Cardiovascular risk factors, the degree of control, complications related to diabetes, antidiabetic therapy and the number of drugs were not associated with the presence of depression. CONCLUSIONS: The prevalence of depression was high in patients with type 2 diabetes. However, in approximately 40% of patients depression was undiagnosed. The complications related to diabetes and antidiabetic therapy were not associated with the presence of depression.

Prevalence of diabetic retinopathy in individuals with type 2 diabetes who had recorded diabetic retinopathy from retinal photographs in Catalonia (Spain).

BACKGROUND/AIMS: Retinal photography with a non-mydriatic camera is the method currently employed for diabetic retinography (DR) screening. We designed this study in order to evaluate the prevalence and severity of DR, and associated risk factors, in patients with type 2 diabetes (T2DM) screened in Catalan Primary Health Care. METHODS: Retrospective, cross-sectional, population based study performed in Catalonia (Spain) with patients with T2DM, aged between 30 years and 90 years (on 31 December 2012) screened with retinal photography and whose DR category was recorded in their medical records. DR was classified as: no apparent retinopathy (no DR), mild non-proliferative DR (mild NPDR), moderate NPDR, severe NPDR, proliferative DR (PDR) and diabetic macular oedema (DMO). Non-vision threatening DR (non-VTDR) included mild and moderate NPDR; VTDR included severe NPDR, PDR and DMO. Clinical data were obtained retrospectively from the SIDIAP database (System for Research and Development in Primary Care). RESULTS: 108 723 patients with T2DM had been screened with retinal photography. The prevalence of any kind of DR was 12.3% (95% CI 12.1% to 12.5%). Non-VTDR and VTDR were present in 10.8% (mild 7.5% and moderate NPDR 3.3%) and 1.4% (severe NPDR 0.86%, PDR 0.36% and DMO 0.18%) of the study patients, respectively. CONCLUSIONS: The prevalence of any type of DR in patients with T2DM screened with retinal photography was lower when compared with earlier studies.

Glycemic control and use of A1c in primary care patients with type 2 diabetes mellitus.

AIMS: To evaluate the degree of glycemic control and its relationship with disease characteristics and antidiabetic treatment in patients with type 2 diabetes mellitus (DM), as well as the frequency of A1c use. METHODS: For this purpose, an observational, cross-sectorial, and multicenter study was performed. A total of 443 patients were monitored in 17 Spanish primary healthcare centers. Demographic and clinical variables were recorded from the clinical history of patients. RESULTS: Mean age was 68.9±12.0 years. Time of evolution of DM was 9.2±6.4 years. Mean A1c was 7.38±1.34% and 45% of patients achieved A1c <7%. There was a no significant relationship between the degree of control and time of evolution of DM. In 16% of patients no A1c determination was performed in the previous twelve months. In those patients in whom A1c was determined, 95% received pharmacologic treatment, and 31% insulin therapy. 66% of patients on monotherapy attained A1C <7%, compared with 39% and 23% of those receiving double- and triple-oral therapy, respectively (p<0.001). Only 21% of patients on insulin therapy achieved A1c <7%. The worst-controlled patients were those receiving oral antidiabetic agents and insulin (24% had A1c levels ≥9%). CONCLUSIONS: A large proportion of patients are poorly controlled. Poor control increases according to complexity of treatment. A1c is underdetermined in many patients, likely related to clinical inertia.

Evaluation of diabetic foot screening in Primary Care.

AIM: To ascertain whether patients with type 2 diabetes are screened for diabetic foot, and to analyze the factors related to patients and centers associated to performance of such screening. MATERIAL AND METHODS: A multicenter, epidemiological, cross-sectional study was conducted. The clinical records of 443 patients with type 2 diabetes monitored at Primary Care for at least 12 months were reviewed. Demographic and healthcare variables and characteristics of the primary care center were recorded. RESULTS: In the previous year, 51.2% of patients had been trained on foot self-care, 56.4% had undergone foot inspection, 39.5% had been examined with a monofilament, and palpation of peripheral pulses and measurement of the ankle-brachial index were performed in 45.8 and 10.1% of patients, respectively. Diabetic foot screening (inspection, monofilament testing, and palpation of peripheral pulses) was performed in 37% of study patients. Ulcer risk stratification was done in 12.4% of patients. A significant association was found between diabetic foot screening and presence of foot deformities (P<.001), history of neuropathy (P=.005), and history of peripheral artery disease (P<.05). Screening was also associated to some characteristics of the center, such as reception of information about goal achievement (P<.001) and economic incentives for goal attainment (P<.001). CONCLUSIONS: Compliance with diabetic foot screening and ulcer risk stratification in patients with type 2 diabetes in Primary Care was poor.

[Inertia and treatment compliance in patients with type 2 diabetes in primary care]. / Inercia y cumplimiento terapéutico en pacientes con diabetes mellitus tipo 2 en atención primaria.

BACKGROUND AND OBJECTIVES: Therapeutic inertia (TI) and therapeutic compliance (TC) are 2 important barriers in achieving the therapeutic objectives recommended for patients with diabetes mellitus type 2 (DM2). This study analyzes the TI in patients with DM2 who do not achieve the glycemic, blood pressure (BP) and LDL-cholesterol (c-LDL) control goals, the patients' TC and the relationship between TI and TC. PATIENTS AND METHODS: This is a descriptive study conducted in a Primary Health Care center. We included 320 diabetic patients. Objectives of control were HbA1c ≤ 7%, blood pressure (BP) ≤ 130/80 mm Hg, c-LDL ≤ 100 mg/dl, TI (when the objectives of control were not reached and the professional did not change the treatment) and TC (by counting withdrawals of pharmacy prescriptions). RESULTS: The objectives of control for HbA1c, BP and c-LDL were reached by 66.4, 43.2 and 40.5% of patients, respectively. There was TI in the 86.4% of patients for c-LDL, in 76.7% for BP and in 40.6% for HbA1c. The percentage of therapeutic non-compliance was of 36.1, 37.5 and 32.0% for antidiabetic, antihypertensive and lipid lowering drugs, respectively. Elderly patients were better compliants. TI and TC were not associated. We did not find differences in the level of control, TI, use of drugs and TC by sex. CONCLUSIONS: TI and TC play an important role in the non-consecution of the control objectives in diabetic patients, especially regarding BP and lipids. TC is not related to TI.