Evolution of the consumption trend of proton pump inhibitors in the Lleida Health Region between 2002 and 2015.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most commonly prescribed pharmacological groups. Their high prevalence and duration of use are of important health concern due to the risk they can cause to patients. Despite these risks, their use remains particularly high, especially in the elderly population. We determined the trend in the prevalence of PPI consumption in the population of the Lleida Health Region between 2002 and 2015 to explore patterns of use and associated characteristics. METHODS: An analysis of secular trends between 2002 and 2015 was performed. The database included all individuals who used PPIs in the Lleida Health Region, which had 358.070 inhabitants in 2015. PPI use was evaluated using prescription dispensing data from the public health system. All types of PPIs approved by the pharmaceutical agency were included. Trends were investigated by age and sex. RESULTS: For the whole study period, a total of 215,417 individuals accounted for 292,122 dispensations. Overall, 48% were women, and the mean age was 62 years. The dispensing prevalence of PPI use in 2015 was 18.0% overall-20.4% for women and 15.7% for men-and was 54.6% for those over 65 years. In terms of the subtypes of PPIs, 16.8% of prescriptions were for omeprazole, 0.66% were for pantoprazole, and 0.48% were for lansoprazole. The evolution of the annual PPIs dispensation prevalence showed a progressive increase from 11.3% in 2002 to 18.0% in 2015, which was attributable to an increase in the use of omeprazole (9.0% vs. 16.8%) and, to a lesser extent, esomeprazole (0.02% vs. 0.4%). CONCLUSION: An increase in the prevalence of PPI dispensation was observed over 14 years of follow-up. The prevalence of dispensation was especially high for the population older than 65 years, despite the risk of cognitive decline and falls. Comprehensive actions are required to to increase rational prescribing of PPIs, especially in high-risk populations.

Trends in the consumption rates of benzodiazepines and benzodiazepine-related drugs in the health region of Lleida from 2002 to 2015.

BACKGROUND: The high prevalence and long-term use of benzodiazepines (BZDs) treatment are debated topics because of the risk they can cause to the patients. Despite the current information on the risk-benefit balance of these drugs, their consumption remains particularly high. We determined the trend in the consumption prevalence of benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs) in the population of the Health Region of Lleida to explore patterns of use and the associated characteristics associated between 2002 and 2015. METHODS: An analysis of secular trends was carried out between 2002 and 2015; the databased included all individuals from the Health Region of Lleida, which had 358,157 inhabitants in 2015, that consumed BZDs. The consumption of BZDs was evaluated using prescription billing data from the Public Health System. All types of BZDs and BZD analogues that had been approved by the drug agency were included. Trends by age and sex were investigated. RESULTS: Over the whole study period, a total of 161,125 individuals accounted for 338,148 dispensations. Overall, 59% were women, and the mean age was 56 years. The dispensing prevalence of BZDs use in 2015 was 14.2% overall -18.8% in women and 9.6% in men-and was 36% in those over 65 years. According to the half-life of BZDs, the prevalence of short-intermediate BZD use, intermediate-long BZD use, and Z-drugs use was 9.7, 5.5 and 0.8%, respectively. The evolution of the annual prevalence of BZD dispensing showed a progressive decline, from 15.3% in 2002 to 14.2% in 2015, which was attributed to a decrease in the consumption of intermediate-long half-life BZDs (8.0% vs. 5.5%) and Z-drugs (1.4% vs. 0.8%). CONCLUSION: The dispensing prevalence of BZDs and Z-drugs was high, although a small reduction was observed during this time period. The dispensing prevalence was especially high in the population over 65, despite the risk of cognitive decline and falls. Integral actions are required to lower the BZD prescription rate.

Cross-sectional study of the association between empathy and burnout and drug prescribing quality in primary care.

OBJECTIVE: The aim of this study was to assess whether burnout and empathy levels among general practitioners (GPs) might influence prescribing performance assessed using pharmaceutical prescription quality standard indicators. DESIGN AND SETTING: Cross-sectional descriptive study of 108 GPs from 22 primary care centers in Lleida, Spain, and of centralized data corresponding to 183 600 patients under their care. The study was conducted between May and July 2014. MAIN OUTCOME MEASURES: Burnout and empathy were measured using the Spanish versions of the Maslach Burnout Inventory and the Jefferson Scale for Physician Empathy, and prescribing quality was measured using the Catalan Pharmaceutical Prescription Quality Standard (EQPF). Normal distribution of scores was verified using the Chi-square and Kolmogorov-Smirnov-Lilliefors tests. The effect of each of the variables was evaluated using crude odds ratios. RESULTS: Older GPs scored significantly higher in the EQPF (P < 0.05). High empathy scores were positively associated with high EQPF scores. GPs with low burnout also performed better in the EQPF. CONCLUSIONS: More empathic, less burned-out, older GPs showed better prescribing performance according to quality indicators. However, further studies are needed to evaluate other factors influencing prescribing habits. The promotion of communication skills may increase empathy and reduce burnout, thus benefiting patients.

CREB controls cortical circuit plasticity and functional recovery after stroke.

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.

Risk factors for exacerbation in chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: Although acute exacerbations are key events in the progression of chronic obstructive pulmonary disease (COPD), their frequency and the factors associated with acute exacerbation are not fully known. OBJECTIVE: To determine the incidence and risk factors of very frequent exacerbations in COPD (⩾3 per year). PATIENTS AND METHODS: In a cohort study to analyse acute exacerbation and associated factors in 512 primary care patients during a 2-year follow-up, variables of interest were collected for each patient. Acute exacerbation was defined as an event that required antibiotics and/or systemic steroids (moderate) or hospital admission (severe). Odds ratios (OR) were used to determine factors associated with exacerbation. RESULTS: Incidence of exacerbation was 61.7% in the first year of follow-up and 63.9% in the second year. During the first year, the factors associated with very frequent exacerbation were previous hospital admission (OR 1.69), dyspnoea (moderate [OR 2.86] and severe-very severe [OR 5.83]) and the Charlson Index (OR 1.19); during the second year, associated factors were female sex (OR 4.17), history of previous hospital admissions (OR 2.90), smoking (smoker/ex-smoker) (OR 2.00) and forced vital capacity (OR 0.98). CONCLUSIONS: Incidence of exacerbation is high in COPD patients. Previous admission for exacerbation is a strong predictor and can identify patients at risk.

Water acidification trends in a reservoir of the Iberian Pyrite Belt (SW Spain).

Scarcity of waters is the main limiting factor of economic development in most arid and semi-arid regions worldwide. The construction of reservoirs may be an optimal solution to assure water availability if the drainage area shows low disturbances. This is the quandary of mining areas where economic development relies on water accessibility. Water acidification trends were investigated in the Sancho Reservoir (SW Spain) in the last 20 years. The acidity (pH3-5) and high dissolved metal concentrations (e.g., 4.4 mg/L of Al, 2.1mg/L of Mn, 1.9 mg/L of Zn) observed in the Sancho, together with the large volume stored (between 37 and 55 Mm(3)), makes this reservoir an extreme case of surface water pollution worldwide. A progressive acidification has been observed since 2003, as evidenced by decreasing pH values and increasing dissolved metal concentrations, especially noticeable after 2007. The increase in the net acidity in the reservoir originates from the higher input of metals and acidity due to the rebound effect after the mining closure in 2001. This trend was not detected in the river feeding the reservoir due to its great hydrological and hydrochemical variability, typical of the Mediterranean climate. Chemical analysis and absolute dating of sediments identified a progressive enrichment in S and metals (i.e., Fe, Zn Cu, Ni, Co and Cd) in the upper 20 cm, which reinforce the year 2002/03 as the onset of the acidification of the reservoir. The decrease of pH values from 4-5 to 3-4 occurred later than the increase in sulfate and metals due to pH-buffering by Al. The acid mine drainage (AMD) pressure has caused an increment of dissolved Fe and other metals, as well as a change in the pH buffering role, exerted now by Fe. These processes were simulated by PHREEQC, which confirms that the acidification trend will continue, causing pH values to reach 2.5 if AMD pressure persists.

Estudio multicéntrico de deterioro cognitivo en lupus eritematoso sistémico: ECLES / Multicenter study of cognitive decline in systemic lupus erythematousus: ECLES

Introducción: los pacientes lúpicos presentan un riesgo incrementado de deterioro cognitivo (DC) comparado con individuos sanos, el cual puede ser debido a múltiples causas. Objetivo: Describir la frecuencia y características del deterioro cognitivo en pacientes con lupus sin manifestaciones neuropsiquiátricas conocidas. Materiales y método: Se incluyeron pacientes de 16 a 55 años con diagnóstico de LES según criterios del Colegio Americano de Reumatología (ACR) de 1997. Se incluyeron test neuropsicológicos acordes a la propuesta del ACR y el cuestionario de Beck para evaluar depresión. Se definió DC a valores de <2 o más desvíos estándar comparada con la media de población normal en al menos un test. Se consideró focal cuando afectó una o más medidas de un dominio y multifocal en 2 o más dominios. Para comparar proporciones se utilizó prueba exacta de Fisher y para comparar variables numéricas se usó prueba de Kruskal-Wallis. Se consideró significativo un valor de p <0,05. Resultados: Se estudiaron 86 pacientes con lupus, el 90% de origen caucásico, 8% mestizos y 1% amerindio. El 82% alcanzó nivel secundario. La frecuencia de DC fue del 65% (56/86). Los dominios afectados: memoria 45%, funciones ejecutivas 30%, atención 29%, lenguaje 4,6%. Se detectó depresión en un 48% de los pacientes. Se analizaron diferentes factores de riesgo, sin hallar diferencias estadísticamente significativas a excepción de la etnia (p=0,02). Conclusión: Se halló una frecuencia elevada de deterioro cognitivo en pacientes con LES, los pacientes no caucásicos tuvieron mayor DC con diferencias significativas en comparación con los pacientes caucásicos.

Background: patients with systemic lupus erythematosus (SLE)have an increased risk of cognitive impairment (CI) compared tohealthy individuals and it may be due to multiple causes. Objective: To determine the frequency and characteristics of CI inlupus patients without known previous neuropsychiatric events. Methods: Patients aged 16 to 55 fulfilling the 1997 ACR criteria forSLE were included. The neuropsychological test battery proposedby the ACR was used to determine CI and Beck depression werealso assessed. CI was defined as values of ≤2 standard deviationscompared to the mean of the general population in at least one test. It was considered focal involvement if it affected one or more measuresof a single domain and multifocal if 2 or more domains wasaffected. To compare proportions, Fisher’s exact test was used andto compare numerical variables, Kruskal-Wallis. A value of p <0.05was considered significant. Results: 86 patients were evaluated, 90% were Caucasian, 8%mestizos and 1% Amerindian. 82% had high school. CI was foundin 65% of patients (56/86). The affected domains were: memory45%, executive functions 30%, attention 29% and language 4.6%. Depression was detected in 48% of patients. Different risk factorswere analyzed and found no statistically significant differences exceptfor ethnicity (p=0.02). Conclusion: A high frequency of CI was found in patients with SLE,non-Caucasian had higher CI with significant differences in comparisonwith Caucasian patients.

Assessment of the dissolved pollutant flux of the Odiel River (SW Spain) during a wet period.

The abandoned mining districts of the Iberian Pyrite Belt (IPB, SW Spain) are an extreme source of pollution by acid mine drainage (AMD) to the Tinto and Odiel rivers. The pollutant flux transported by the Odiel River during a high stage period was assessed using concentration-discharge relationships and concentration-conductivity relationships, for the hydrological year 2009/10 (which was especially wet). Both correlations were high (R(2)>0.80) for most of the elements studied. The two methods for flux calculation gave similar results with differences generally lower than 10%. The dissolved contaminant flux transported by the Odiel River just before its mouth mainly includes sulphate (257,534±13,464 t/yr), Al (13,259±1071 t/yr), Zn (4265±242 t/yr), Mn (2532±146 t/yr) and Cu (1738±136 t/yr), and minor amounts of other elements. These findings confirm that, up to our knowledge, the Odiel River can be considered to be the largest contributor of mining-related pollutants to the world's oceans.

Metal cycling during sediment early diagenesis in a water reservoir affected by acid mine drainage.

The discharge of acid mine drainage (AMD) into a reservoir may seriously affect the water quality. To investigate the metal transfer between the water and the sediment, three cores were collected from the Sancho Reservoir (Iberian Pyrite Belt, SW Spain) during different seasons: turnover event; oxic, stratified period; anoxic and under shallow perennially oxic conditions. The cores were sliced in an oxygen-free atmosphere, after which pore water was extracted by centrifugation and analyzed. A sequential extraction was then applied to the sediments to extract the water-soluble, monosulfide, low crystallinity Fe(III)-oxyhydroxide, crystalline Fe(III)-oxide, organic, pyrite and residual phases. The results showed that, despite the acidic chemistry of the water column (pH<4), the reservoir accumulated a high amount of autochthonous organic matter (up to 12 wt.%). Oxygen was consumed in 1mm of sediment due to organic matter and sulfide oxidation. Below the oxic layer, Fe(III) and sulfate reduction peaks developed concomitantly and the resulting Fe(II) and S(II) were removed as sulfides and probably as S linked to organic matter. During the oxic season, schwertmannite precipitated in the water column and was redissolved in the organic-rich sediment, after which iron and arsenic diffused upwards again to the water column. The flux of precipitates was found to be two orders of magnitude higher than the aqueous one, and therefore the sediment acted as a sink for As and Fe. Trace metals (Cu, Zn, Cd, Pb, Ni, Co) and Al always diffused from the reservoir water and were incorporated into the sediments as sulfides and oxyhydroxides, respectively. In spite of the fact that the benthic fluxes estimated for trace metal and Al were much higher than those reported for lake and marine sediments, they only accounted for less than 10% of their total inventory dissolved in the column water.

Comparative exposure to antipsychotic medications in immigrant and native-born populations of a Spanish health region.

BACKGROUND: Raised rates of psychoses among ethnic minorities have been reported. Exposure to antipsychotic medications can give information on mental illness management and ethnic-related differences. OBJECTIVE: To compare exposure to antipsychotic medications in immigrant and native-born populations in Spain. METHOD: Descriptive cross-sectional study of the dispensation of antipsychotic medications to the population aged 15 to 64years, in a Spanish Health Region during 2008. RESULTS: 1.9% of the native-born population was exposed to antipsychotic medications as compared to 0.4% of the immigrant population. Native-born women were exposed from 1.8 to 5.3 times more and native-born men from 3.6 to 6.3 times more than immigrants of the same gender. The least exposed were persons from Eastern Europe and men from sub-Saharan Africa. Active ingredients prescribed were similar between the two groups. Of the immigrant group, 15.7% were admitted to a psychiatric ward as compared to 6.4% of the native-born population. In the former, non-specific diagnoses were predominant. CONCLUSIONS: All immigrant groups had lower exposure to antipsychotic medications, were admitted to inpatient care more often and had less specific diagnoses. Both diagnostic processes and adherence to treatment need improvement in the regional immigrant population.

Management by objectives and its impact on specialist prescription quality at discharge and in external consultations.

OBJECTIVE: To verify that implementing a policy of management by objectives, based on collaboration between hospital pharmacy, primary care and specialised medical managers, improves prescription quality indicators in specialised care and reduces unwanted "induced" prescriptions (i.e. those issued by specialists, hospital doctors or the patients themselves) in primary care. METHOD: A four year quasi-experimental controlled intervention study on prescription at discharge and in outpatient hospital consultations was conducted. In hospital A, a quality cycle was applied: assessment, identifying improvement opportunities, implementing corrective actions and re-assessment. However, it was not applied in control hospital B. The indicators chosen were the percentage of generic medicines prescribed, the percentage of prescriptions for new therapies with no added value and the percentage of prescriptions for ACE inhibitors recommended. RESULTS: In hospital A, an increase in indicators 1 and 3 has been observed, both being statistically significant, between the last year of intervention and the year previous to intervention. Hospital A managed to reduce indicator 2 to 4.5%, while this indicator increased in hospital B to 8.8%. Furthermore, a statistically significant difference in indicators between the two hospitals has been registered. CONCLUSION: Pay-for-Performance programs in prescription practices of hospital physicians are effective actions to improve quality indicators of medication use.

Duration and adherence of antidepressant treatment (2003 to 2007) based on prescription database.

BACKGROUND: Many patients discontinue antidepressant therapy long before the six-month minimum duration recommended for the treatment of major depression and many other diagnoses. PURPOSE: To estimate the duration of antidepressant treatment and to analyse the following factors in relation to treatment adherence: age, sex, polypharmacy and type of drug. METHODS: Retrospective cohort followed up for five years (2003-2007) based on prescription database. SELECTION CRITERIA: Users who had received at least one antidepressant prescription in 2003 and who had not received antidepressants during the previous 12 months. VARIABLES STUDIED: Age, sex, drug, polypharmacy, period of treatment, packs dispensed. Adequate adherence was defined as dispensation of medication during at least 80% of the treatment period, and compliance was defined as good when, in addition, the treatment lasted more than four months. RESULTS: Of the 7525 patients selected, 56% abandoned medication during the first four months. Men were more likely to give up medication before time than women. Good compliance was recorded in 22% of patients and was twice as frequent in patients with high levels of polypharmacy than in those with low levels (31% vs. 15.3%). Patients receiving maprotiline, venlafaxine, mirtazapine, citalopram, clomipramine and fluoxetine presented the highest percentages of good compliance. CONCLUSIONS: Only one out of five patients complied with treatment for over four months. Treatment periods were shorter in men. In chronic processes, patients receiving polypharmacy presented the best compliance.

A kinetic approach to caffeine--Coffea cruda interaction.

The biological effect of Coffea cruda 30c was investigated in rats pre and post treated with caffeine. The experimental subjects were male Wistar rats. Caffeine was administered intraperitoneally at the beginning of a sleep period. Coffea cruda 30c (0.1 ml) was administered orally, a contemporaneous control group was tested. The Electroencephalogram (EEG) was recorded in the parietal region during the following sleep cycle. The effect was evaluated by three EEG parameters: the spectral power in delta (0.5-2.5 Hz) and slow 0.32-0.48 Hz bands and the slow/delta power ratio. These markers were analyzed vs time for control and homeopathic groups, blind. In the pretreated set, a similar pattern was identified for control and verum groups up to the 4th hour. From the 5th hour on, power in the delta band was statistically higher in the verum. Spectral power in the slow band and power ratio for the verum group was smaller than the control group from the 6th hour on. In the post-treated set, two verum sub-groups were identified: Post v-A: did not exhibit significant differences from control; Post v-B: displayed an opposite tendency than pre-treatment verum. We conclude that Coffea cruda 30c modifies sleep pattern increasing sleep intensity with pre-treatment. In a subset of the post-treated animals Coffea 30c appeared to reinforce the effects of caffeine.

Proteus syndrome: new findings in seven patients.

Seven children with Proteus syndrome (PS) are reported. The majority of clinical findings coincide with what is reported in the literature. New findings were blue sclerae, telecanthus, epiblepharon, endotropy, hemimegaly of the optic nerve, occipital dysmyelination and compression of the corpus callosum, craneosynostosis, decalcification and thinning of the cortical layer of long bones, and talipes equinus. The clinical findings, possible etiology, differential diagnosis, and treatment of PS are discussed.

Giant congenital melanocytic nevi, neurocutaneous melanosis and neurological alterations.

BACKGROUND: Magnetic resonance imaging (MRI) findings suggestive of neurocutaneous melanosis (NCM) have been reported in asymptomatic patients with giant congenital melanocytic nevi (GCMN). OBJECTIVE: To investigate the presence of NCM and the clinical neurologic status of patients with GCMN involving the head an neck. METHODS: Thirteen patients with GCMN involving the head and neck were clinically examined by pediatric specialists in dermatology, ophthalmology and neurology. Electroencephalograms, noncontrasted and contrasted computerized tomography (CT) scans and MRI were performed. RESULTS: Eleven of 13 patients with GCMN of the head and neck previously considered asymptomatic were found to present mild but evident neurologic alterations. No signs of NCM were found in the CT scans or in the MRI. CONCLUSIONS: Patients with GCMN of the head and neck may have associated neurologic alterations not related to the presence of neurocutaneous melanosis.

Effects of heparin on wound healing.

Heparin, an anticoagulant that is widely used for cardiac patients, has been studied to determine its effects on wound healing. The role of heparin in wound healing has been demonstrated in both in vitro and in vivo studies. In cell culture studies, heparin and growth factors are associated with rapid and effective endothelial cell repair. In clinical studies, patients with burns and those with diabetic foot ulcers showed an increase in capillary circulation and decreased healing time. In contrast, heparin may not be beneficial in populations with ischemia, malnourishment, and vascular problems, although research in these populations is limited. Nevertheless, heparin continues to have therapeutic advantages for wound healing in carefully selected patients.

Sequence and functional analysis of the Streptomyces phaeochromogenes plasmid pJV1 reveals a modular organization of Streptomyces plasmids that replicate by rolling circle.

pJV1 is an 11 kb, high-copy-number conjugative Streptomyces phaeochromogenes plasmid that replicates by the rolling circle mechanism (RCR). Sequencing combined with functional analysis of deletion, insertion and frameshift mutations was used to characterize the genes involved in plasmid transfer and chromosome mobilization (Cma), the single-strand origin for RCR and an associated strong incompatibility (Sti) determinant. pJV1 contains two essential transfer genes whose expression is regulated by an adjacent repressor gene with similarity to the GntR family of regulators. A consensus sequence specific for the helix-turn-helix motifs of repressor proteins of Streptomyces plasmids is proposed. Unregulated expression of the transfer genes by inactivation of the repressor is lethal. Three additional genes increase intramycelial plasmid spread resulting in pock formation but, unlike the essential transfer genes, are not required for Cma. The pJV1 transfer genes and their regulatory region, but not the minimal replication region encoding the double-strand replication origin and replication protein, are similar in their sequence and arrangement to those of the Streptomyces nigrifaciens plasmid pSN22, revealing a modular organization of Streptomyces RCR plasmids.

Intravesical BCG therapy of superficial bladder cancer: study of adverse effects.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) has proved to be more effective than most chemotherapeutic agents in the prophylaxis and treatment of superficial bladder tumours. Side-effects, both local and systemic, are the main limitations against its use. With the aim of lowering the incidence and severity of side-effects, we started to use two vials of BCG, Connaught type, per instillation, instead of three vials, as recommended by the manufacturer. We prospectively reviewed adverse effects of BCG treatment at the lower dosage in 92 patients. Compared with other series, we found a similar incidence of adverse effects except for some local effects as haematuria which showed a higher incidence, but we also found a lower rate of tumour relapse. Four primary tumours were recorded during the study period. In our open study, a lower BCG intravesical dosage is not followed by a reduction in side-effects.