The effect of external stimulation on functional networks in the aging healthy human brain.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.

Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

The Aging Imageomics Study: rationale, design and baseline characteristics of the study population.

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged ≥50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

The Role First-Day Readings Play in a 3-Day Schedule of Self-Monitoring Home Blood Pressure Based on Prognostic Data. VAMPAHICA Study.

BACKGROUND: The optimal schedule for self-monitoring home BP (SMHBP) readings is enormously important in the diagnosis of different phenotypes related to hypertension. The aim of this study was to determine the prognostic capacity of a 3-day SMHBP schedule when using or suppressing the first-day measurements in compiling the results. METHODS: A total of 767 newly diagnosed, nontreated patients with no history of cardiovascular disease (CVD) were followed for 6.2 years. As a baseline, office BP measurements were taken for all the patients who then went on to follow a 3-day SMHBP schedule, taking 2 readings in the morning and 2 in the evening. The prognostic calculation was performed with CVD variables. The prognostic capacity of the 3-day schedule was evaluated with and without the first-day readings (12 and 8 readings). RESULTS: A total of 223 normotensive subjects (NT), 271 subjects with sustained hypertension (SHT), and 184 white-coat hypertensive subjects (WCH) were followed. The distribution of 98 (14.4%) nonfatal CV events during the follow-up was as follows: WCH 21 (11.4%), NT 9 (4.0%), and SHT 68 (25.1%). No statistically significant differences were observed in the risk of CV events (OR) for the 2 groups of hypertensives, irrespective of the schedule of readings used (SHT with vs. without first-day readings: 8.81 (4.28-18.15) vs. 8.61 (4.15-17.85) and WCH with vs. without first-day readings: 2.71(1.13-6.47) vs. 3.40 (1.49-7.78)). CONCLUSIONS: Our findings show that first-day readings do not need to be discarded in order to calculate the final value of an SMHBP schedule.

Analysis of the location of retinal lesions in central retinographies of patients with Type 2 diabetes.

PURPOSE: To describe the distribution of Type 2 DM retinal lesions and determine whether it is symmetrical between the two eyes, is random or follows a certain pattern. METHODS: Cross-sectional study of Type 2 DM patients who had been referred for an outpatients' ophthalmology visit for diabetic retinopathy screening in primary health care. Retinal photographic images were taken using central projection non-mydriatic retinography. The lesions under study were microaneurysms/haemorrhages, and hard and soft exudates. The lesions were placed numerically along the x- and y-axes obtained, with the fovea as the origin. RESULTS: From among the 94 patients included in the study, 4770 lesions were identified. The retinal lesions were not distributed randomly, but rather followed a determined pattern. The left eye exhibited more microaneurysms/haemorrhages and hard exudates of a greater density in the central retina than was found in the right eye. Furthermore, more cells containing lesions were found in the upper temporal quadrants, (especially in the left eye), and tended to be more central in the left eye than in the right, while the hard exudates were more central than the microaneurysms/haemorrhages. CONCLUSION: The distribution of DR lesions is neither homogeneous nor random but rather follows a determined pattern for both microaneurysms/haemorrhages and hard exudates. This distribution means that the areas of the retina most vulnerable to metabolic alteration can be identified. The results may be useful for automated DR detection algorithms and for determining the underlying vascular and non-vascular physiopathological mechanisms that can explain these differences.

High levels of fasting glucose and glycosylated hemoglobin values are associated with hyperfiltration in a Spanish prediabetes cohort. The PREDAPS Study.

AIM: This study aimed to investigate whether different levels of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) in prediabetes are associated with hyperfiltration. METHODS: A prospective cohort of 2,022 individuals aged 30-74 years took part in the PREDAPS Study. One cohort of 1,184 participants with prediabetes and another cohort of 838 participants with normal FPG and normal HbA1c were followed for 5 years. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile for healthy control participants, while hypofiltration was defined as an eGFR below the 5th percentile. The prevalence of hyperfiltration was compared for different levels of prediabetes: level 1 of prediabetes: FPG <100 mg/dL plus HbA1c 5.7-6.0% or FPG 100-109 mg/dL plus HbA1c < 5.7%; level 2 of prediabetes: FPG <100 mg/dL plus HbA1c 6.1-6.4% or FPG 100-109 mg/dL plus HbA1c 5.7-6.0% or FPG 110-125 mg/dL plus HbA1c <5.7% and level 3 of prediabetes: FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4%. RESULTS: The participants with hyperfiltration were significantly younger, had a higher percentage of active smokers, and lower levels of hemoglobin and less use of ACEIs or ARBs. Only level 3 prediabetes based on FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4% had a significantly higher odds ratio (OR) of hyperfiltration (OR 1.69 (1.05-2.74); P < 0.001) compared with no prediabetes (FPG < 100 mg/dL and HbA1c < 5.7%) after adjustment for different factors. The odds ratios for different levels of HbA1c alone in prediabetes increased progressively, but not significantly. CONCLUSIONS: Level 3 of prediabetes based on FPG 100-109 mg/dL plus HbA1c 6.1-6.4% or FPG 110-125 mg/dL plus HbA1c 5.7-6.4% had a significantly higher OR of hyperfiltration compared with participants without prediabetes.

The effects of copayment in primary health care: evidence from a natural experiment.

OBJECTIVE: Evaluate the effects of the 'euro per prescription' on primary health care services (number of doctor visits), through a retrospective cohort study of health care users in Catalonia (Spain). This policy, implemented in Catalonia on 23 June 2012, only lasted 6 months. This policy was introduced to improve budgetary imbalances in Spain and boost the regional and national governments' budgets. METHODS: We used a retrospective cohort, composed of individuals who had had contact with primary healthcare services between January 1, 2005 and December 31, 2012. The econometric specification followed is a hurdle model. RESULTS: Our results show that from October 2012 onwards there was a decrease in the average number of overall visits, particularly for individuals aged 65 years or more. However, this decline cannot be entirely attributed to the introduction of the euro per prescription policy as in October of that same year the Spanish government introduced its pharmaceutical copayment for pensioners. CONCLUSIONS: The policies appraised in this paper reveal a clear deterrent effect among vulnerable individuals such as those with the highest probability of being unemployed and/or those individuals with chronic conditions.

What is the optimal cut-off threshold in self-home blood pressure measurement?: A cohort study according to STROBE statement.

Two aspects arise concerning the use of self-measured blood pressure monitoring to diagnose white-coat hypertension (WCH): the presence of target organ damage (TOD) and the normal cut-off threshold. This study aims to evaluate the cardiovascular risk of WCH according to different self-measured blood pressure normal cut-off thresholds and the influence of TOD at baseline.In all, 678 patients were followed for 6.2 years; 223 normotensive patients, 271 patients with sustained hypertension (HT), and 184 with WCH. TOD was defined as: left ventricular hypertrophy according to ECG, albuminuria, or low estimated glomerular filtration rate. The risk for different cutting points of self-measured blood pressure (<135/85 mm Hg, <130/85 mm Hg, and <130/80 mm Hg) has been determined.The patients with HT experienced an increase in cardiovascular risk and death higher than the normotensive patients (odds ratio [OR] 7.9, 95% confidence interval [CI] 3.8-16.2 for sustained HT; and OR 3.5, 95% CI 1.6-7.4 for WCH). This was observed for all the cut-off thresholds analyzed. In white-coat hypertensive patients (cut-off <135/85 mm Hg) with TOD, the risk was higher than in normotensive patients (OR 4.5; 95% CI 1.9-10.6). Using a self-monitoring blood pressure cut-off threshold of <130/80 mm Hg without TOD at baseline, the WCH cases exhibited no differences in risk to the normotensive patients (OR 2.0, 95% CI 0.5-7.7).The decisions being taken for patients with WCH based on the presence of TOD and a self-administered home monitoring blood pressure measurement cut-off point probably lower than the one that is currently recommended.

Prognostic Value of the Estimated Glomerular Filtration Rate Decline in Hypertensive Patients Without Chronic Kidney Disease.

BACKGROUND: Our objective of this study was to determine if rate of estimated glomerular filtration rate (eGFR) decline and its intensity was associated with cardiovascular risk and death in patients with hypertension whose baseline eGFR was higher than 60 ml/minute/1.73 m2. METHODS: This study comprised 2,516 patients with hypertension who had had at least 2 serum creatinine measurements over a 4-year period. An eGFR reduction of ≥10% per year has been deemed as high eGFR and a reduction in eGFR of less than 10% per year as a low decline. The end points were coronary artery disease, stroke, transitory ischemic accident, peripheral arterial disease, heart failure, atrial fibrillation, and death from any cause. Cox regression analyses adjusted for potentially confounding factors were conducted. RESULTS: A total of 2,354 patients with low rate of eGFR decline and 149 with high rate of eGFR decline were analyzed. The adjusted model shows that a -10% rate of eGFR decline per year is associated with a higher risk of the primary end point (HR 1.9; 95% CI 1.1-3.5; P = 0.02) and arteriosclerotic vascular disease (HR 2.2; 95% CI 1.2-4.2; P < 0.001) in all hypertensive groups. The variables associated to high/low rate of eGFR decline in the logistic regression model were serum creatinine (OR 3.35; P < 0.001), gender, women (OR 15.3; P < 0.001), tobacco user (OR 1.9; P < 0.002), and pulse pressure (OR 0.99; P < 0.05). CONCLUSIONS: A rate of eGFR decline equal to or higher than -10% per year is a marker of cardiovascular risk for patients with arterial hypertension without chronic kidney disease at baseline. It may be useful to consider intensifying the global risk approach for these patients.

Duration and dosing of Proton Pump Inhibitors associated with high incidence of chronic kidney disease in population-based cohort.

BACKGROUND: Proton Pump Inhibitors (PPIs) have been associated with chronic kidney disease (CKD). Our objective was to quantify the association between PPI use and incident CKD in a population-based cohort. METHODS AND FINDINGS: We used a population-based retrospective cohort, including people aged 15 years or over, between January 1, 2005 and December 31, 2012. PPI use was measured in a follow-up session by recording prescriptions. Incident CKD was defined as an estimated glomerular filtration rate < 60 ml/ min/1.73 m2 and/or urinary albumin level to creatinine level ≥ 30 mg/g, in two or more determinations over a period of at least 3 months of the follow-up. Proton Pump Inhibitor use was associated with incident CKD in analysis adjusted for different clinical variables (Hazard Ratio (HR) 1.18; 95% CI 1.04-1.51) in individuals who used PPI in the basal visit (HR 1.37; 95% CI 1.25-1.50) and in those who started to use PPI during the follow-up. High doses of PPI increased the risk of incident CKD (HR 1.92; 95%CI 1.00-6.19) for any type of exposure to PPIs (HR 2.40; 95%CI 1.65-3.46) and for individuals who used high doses throughout the follow-up. This risk of incident CKD increased after three months' exposure to PPIs, (HR1.78; 95% CI 1.39-2.25) between the third and sixth months and (HR 1.30; 95%CI 1.07-1.72) after the sixth month. CONCLUSIONS: PPI use is associated with a higher risk of incident CKD. This association is greater for high doses and becomes apparent after three months' exposure.

Prediabetes is associated with glomerular hyperfiltration in a European Mediterranean cohort study.

BACKGROUND: Glomerular hyperfiltration is well recognized as an early renal alteration in subjects with diabetes mellitus. However, what is not well-known is whether hyperfiltration also occurs in the early stages of hyperglycaemia, for instance in prediabetes. Identifying subjects with glomerular hyperfiltration from among those with prediabetes might be helpful to implement preventive and therapeutic strategies. This study aimed to investigate the association of prediabetes with glomerular hyperfiltration and its associated variables. METHODS: A representative sample of 9238 people aged ≥ 30 years and whose entire clinical and laboratory data were available, were included in this study. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: After adjustment for age, gender, body mass index, systolic blood pressure and diastolic blood pressure, cholesterol, log (triglycerides), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum uric acid, smoking status, hypertension, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, fasting plasma glucose (FPG) was found to be independently positively associated with eGFR. The hazard ratios (95% confidence interval) for hyperfiltration were 1.61 (1.28-2.03) and 2.30 (1.89-2.79) for prediabetes and diabetes, respectively, when compared with participants with normoglycemia. CONCLUSION: Prediabetes was associated with glomerular hyperfiltration. Longitudinal studies are needed to investigate whether hyperfiltration in prediabetes is associated with a later decline in eGFR.

Effect of effervescent paracetamol on blood pressure: a crossover randomized clinical trial.

OBJECTIVE: To evaluate the effect of effervescent paracetamol on office and ambulatory blood pressure (BP) compared with noneffervescent paracetamol in hypertensive patients. DESIGN: This was a multicenter open crossover randomized clinical trial. SETTING: Primary care centers in Catalonia and the Basque Country. PARTICIPANTS: Inclusion criteria were office BP 150/95 mmHg or less and daytime ambulatory BP 140/90 mmHg or less, stable pharmacologic or nonpharmacologic antihypertensive treatment, and concomitant chronic osteoarticular pain. INTERVENTIONS: Baseline randomized assignment to 3-week periods of effervescent paracetamol (1 g three times a day) first and noneffervescent paracetamol later, or inversely, during a 7-week study period. At the start and end of each treatment period, 24-h ambulatory BP monitoring was performed. MAIN OUTCOME MEASURES: Differences in 24-h SBP between baseline and end of both treatment periods. The main analyses were performed according to the intention-to-treat principle. RESULTS: In intention-to-treat analysis, 46 patients were analyzed, 21 were treated with paracetamol effervescent and noneffervescent later, and 25 followed the opposite sequence. The difference in 24-h SBP between the two treatments was 3.99 mmHg (95% confidence interval 1.35-6.63; P = 0.004), higher in the effervescent paracetamol treatment period. Similarly, the per-protocol analysis showed a difference in 24-h SBP between the two groups of 5.04 mmHg (95% confidence interval 1.80-8.28; P = 0.004), higher in the effervescent paracetamol treatment period. Self-reported pain levels did not differ between groups and did not vary by treatment period. No serious adverse events were reported in either study arm. CONCLUSION: Effervescent paracetamol tablets are responsible for a significant daytime and overall increase in ambulatory 24-h SBP. TRIAL REGISTRATION: NCT: 02514538 EudraCT: 2010-023485-53.

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.

The dynamic behaviour of metabolic syndrome and its components in an eight-year population-based cohort from the Mediterranean.

BACKGROUND: The significant rise in the prevalence of obesity coincides with the considerable increase in the prevalence of metabolic syndrome (MS) currently being observed worldwide. The components of MS are not static and their dynamics, such as the order of their occurrence, or the time of exposure to them are, as yet, unknown but could well be clinically relevant. Our objective was to study the dynamic behaviour of MS and its components in a large population-based cohort from a Mediterranean region. METHODS AND FINDINGS: Our study employed a retrospective cohort (between January 1, 2005 and December 31, 2012) made up of individuals from the general population in a region in the northeast of Catalonia, Spain. Given that most of the explicative variables of the risk of having MS were time dependent and, therefore, the risk was not proportional, we used the Andersen-Gill (AG) model to perform a multivariate survival analysis and inferences were performed using a Bayesian framework. Thirty-nine percent of the participants developed MS; 44.6% of them with a single limited episode. Triglycerides and low HDL cholesterol, together with obesity, are components associated with the first occurrence of MS. Components related to the metabolism of glucose are associated with a medium risk of having a first episode of MS, and those related to blood pressure are associated with a lower risk. When the components related to blood pressure and the metabolism of glucose appear first, they determine the appearance of the first episode of MS. The variables concerning the persistence of MS are those that correspond to clinical conditions that do not have well-established drug treatment criteria. CONCLUSIONS: Our results suggest that the components related to the metabolism of glucose and to high blood pressure appear early on and act as biomarkers for predicting MS, while the components related to obesity and dyslipidaemia, although essential for the development of MS, appear later. Making lifestyle changes reduces the conditions associated with the persistence of MS.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.

BACKGROUND: The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with best performance of the drugs will improve management of hypertensive patients. OBJECTIVE: To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. STUDY ELIGIBILITY CRITERIA: Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data. STUDY APPRAISAL AND SYNTHESIS METHODS: Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework. MAIN OUTCOME(S) AND MEASURE(S): Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. RESULTS: Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats. LIMITATIONS: Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses. CONCLUSIONS AND IMPLICATIONS: Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised.

Effects of the Financial Crisis on Psychotropic Drug Consumption in a Cohort from a Semi-Urban Region in Catalonia, Spain.

PURPOSE: Evidence of whether the recent economic crisis has or has not had an effect on psychotropic drug consumption is very scarce. Our objective was to determine if there had in fact been an increase in psychotropic drug use as a result of the financial crisis. METHODS: In our study a retrospective cohort (between January 1, 2005, and December 31, 2012) was made up of individuals from the general population in a region in the northeast of Catalonia, Spain. We specified a generalized linear mixed model along with combined 'selection on observables' as (propensity scoring) matching and 'selection on unobservables' as (random coefficient) the panel data model methods, and performed inferences using a Bayesian framework. RESULTS: In the period following the economic crisis (post 2009), there was an increase in the consumption of psychotropic drugs which was significantly higher among those who had already been consuming psychotropic drugs prior to 2009 and those most likely to be unemployed. The increase was of greater significance when consumption was measured by the number of drugs being taken, rather than by the defined daily dose (DDD), with the greatest increase occurring in 2011; the very year in which Spain was most affected by the crisis. CONCLUSIONS: Once the financial crisis had ended, there was an increase in the severity, rather than the intensity, of mental health disorders in individuals who had already had disorders before the crisis. This increase occurred in those most likely to be unemployed, and the severity was accentuated in the toughest year of the economic crisis.

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes.

PURPOSE: To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain). METHODS: This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73 m2 and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy. RESULTS: CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4-1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300 mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6-2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73 m2 [OR], 95% confidence interval [CI], 1.3 (1.1-1.6). CONCLUSIONS: These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.

Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications?

AIM: To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. METHODS: Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. RESULTS: Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. CONCLUSION: Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM.