Reducing preoperative anxiety in parents of surgical patients.

Aims and objectives: To investigate preoperative anxiety in parents of paediatric surgical patients, testing whether the provision of information (using video and story books) regarding the surgical process can impact on reducing anxiety. Analyse if any personal factors influence the reduction of anxiety. Background: Attending a surgical theatre generates anxiety, especially in the case of children. The effect of different preoperative intervention procedures in children that attempt to reduce their anxiety level have been studied a great deal. However, although their parents also suffer high levels of anxiety, potential intervention to reduce their levels has not received the same attention. Study design: Randomised Clinical trial. Methods: One hundred and twenty-five parents of children (8-12 y.o.) undergoing surgery in a public hospital were randomly assigned to the control group CG (34 individuals) or one of the 3 experimental groups EG (91). In this Randomised Controlled Study, children and parents of the experimental groups were provided with a story book, a video with additional information of nursing, or both. Prior to the surgical intervention, the State Anxiety, S-A, and Trait Anxiety, T-A, of the parents and children were measured using the STAI and STAIC questionnaires respectively. Data collection was carried out for 12 months starting in October 2016. Results: Parents' S-A in the control group was higher than in the experimental groups. A linear model explains the parents' S-A using as regressors: children S-A, age and T-A of the parents, and children age. Conclusions: Providing information about the surgical process (through stories or videos) to which a child is going to be subjected can reduce the anxiety of the parents. Relevance to clinical practice: Given their close connection to the patient and the potential effects on the children of their psychological situation, healthcare professionals should consider paying greater attention to communicating with the parents.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

Chiral bioanalytical methods in bioequivalence studies of intravenous vs. oral formulations of ibuprofen.

According to the Ibuprofen Product-Specific Bioequivalence Guidance of the European Medicines Agency, achiral bioanalytical methods are considered acceptable for demonstration of bioequivalence of ibuprofen-containing products. The aim of this investigation is to compare the bioequivalence outcomes obtained with individual R and S ibuprofen enantiomers and the sum of both enantiomers from bioequivalence studies in which new intravenous ibuprofen products were compared with oral ibuprofen products. Bioequivalence was assessed for S and R enantiomers of ibuprofen and the sum of both enantiomers, which was calculated to represent the results that would have been obtained with an achiral assay. The infusion rates of 15, 20, and 30 minutes modify the maximum concentration (Cmax ) of the intravenous administrations. In contrast, the time when the maximum concentration is observed (Tmax ) was insensitive to detect differences in input rate within this range of infusion times. The eutomer S-ibuprofen is the least sensitive analyte to detect differences in input rate; therefore, the regulatory acceptance of achiral bioanalytical methods for ibuprofen bioequivalence studies is justified because the sum of both enantiomers is more discriminative than the chiral methods where only the eutomer is used for regulatory decisions.

Effect of enantiomerism on the bioequivalence of a new ibuprofen 600-mg tablet formulation obtained by roller compaction.

The bioequivalence of a new ibuprofen 600-mg film-coated tablet obtained by roller compaction was studied in a crossover study with 22 healthy volunteers. Bioequivalence was analyzed based on (a) the S-enantiomer, (b) the R-enantiomer, and (c) the sum of both enantiomers (representing the results of an achiral assay). The bioequivalence conclusion for ibuprofen products should be based not only on AUC and Cmax but also on tmax since tmax is related to the onset of action. However, it is not possible to ensure if bioequivalence has been demonstrated for tmax as regulators have not defined the acceptance range for the difference between medians of tmax in those cases, where tmax is clinically relevant. In this study, it was possible to conclude bioequivalence for tmax based on S-ibuprofen, though this conclusion might be questioned if the decision is based on R-ibuprofen or the achiral method.

Effect of Roux-en-Y gastric surgery on ciprofloxacin pharmacokinetics: an obvious effect?

PURPOSE: To evaluate pharmacokinetic parameters of ciprofloxacin in patients undergoing Roux-en-Y gastric surgery (RYGS). METHODS: Controlled, single-dose, open-label study in patients undergoing RYGS. Healthy overweight/obese patients 18-60 years old were included. The assessment was performed once in control patients and three times in case patients (before surgery and 1 and 6 months after surgery). In each visit, the subjects received a single oral dose of ciprofloxacin 500 mg. Venous blood samples were obtained at baseline and 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 8 and 14 h after ciprofloxacin intake. Pre- and post-surgery variables were compared using paired ANOVA or the Wilcoxon tests and control vs cases using ANOVA or Mann Whitney. Given the post-surgery change in body weight, the parameters were corrected by dose (mg)/body weight (kg). The analysis was performed using SPSS. RESULTS: Ciprofloxacin Cmax was significantly reduced 1 month after surgery (1840.9 ± 485.2 vs 1589.6 ± 321.8 ng/ml; p = 0.032) but not 6 months after. Cmax on the sixth month was lower than Cmax in control group (2160.4 ± 408.6 vs 1589.6 ± 321.8 ng/ml; p < 0.001). After correcting by the dose (mg)/patient's body weight, both Cmax and AUClast showed significant decrease 1 and 6 months after surgery: Cmax, 289.1 ± 65.3 and 263.5 ± 52.1 (ng/ml)/(dose (mg)/weight (kg)) respectively vs 429.3 ± 127.6 (ng/ml)/(dose (mg)/weight (kg)) at baseline; AUC, 1340.6 ± 243.0 and 1299.2 ± 415.4 (h × ng/ml)/(dose (mg)/weight (kg)) respectively vs 1896.7 ± 396.8 (h × ng/ml)/(dose (mg)/weight (kg)) at baseline. Cmax 1 month post-surgery showed lower values than the control group (375.4 ± 77.4 vs 263.5 ± 52.1 ng/ml; p < 0.001). CONCLUSION: Ciprofloxacin absorption is impaired 1 month and 6 months after RYGS. The effect on Cmax and AUClast faded on the sixth month due to weight loss. It is no necessary to modify the doses of ciprofloxacin in these patients.

[Suspected vascular ehlers danlos syndrome. Case report]. / Sospecha diagnóstica de síndrome de Ehlers Danlos tipo vascular: reporte de un caso y revisión de literatura.

Ehlers Danlos Syndrome comprises a heterogeneous group of genetic disorders of the connective tissue, due to defects in collagen or its modifying enzymes. We report a 21 years old male presenting with translucent skin revealing the subcutaneous venous pattern. He had a thin face, large-appearing eyes, thin lips, thin nose, joint hypermotility and history of hip dysplasia. A vascular Ehlers Danlos Syndrome was suspected. However, the genetic study to confirm the diagnosis was not done.

Sospecha diagnóstica de síndrome de Ehlers Danlos tipo vascular: reporte de un caso y revisión de literatura / Suspected vascular ehlers danlos syndrome: case report

Ehlers Danlos Syndrome comprises a heterogeneous group of genetic disorders of the connective tissue, due to defects in collagen or its modifying enzymes. We report a 21 years old male presenting with translucent skin revealing the subcutaneous venous pattern. He had a thin face, large-appearing eyes, thin lips, thin nose, joint hypermotility and history of hip dysplasia. A vascular Ehlers Danlos Syndrome was suspected. However, the genetic study to confirm the diagnosis was not done.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Adverse drug reactions in neonates: a prospective study.

AIM: To investigate the frequency and characteristics of adverse drug reactions (ADRs) in hospitalised neonates to obtain a better understanding of and improvement in neonatal healthcare. METHODOLOGY: A prospective cohort study. Data were collected on 313 neonates and 2166 drug prescriptions. Clinical characteristics of patients, drugs administered and ADRs were prospectively recorded and analysed. Informed consent was obtained in all cases. RESULTS: 116 different ADRs were detected. 17% of the neonates experienced at least one of these ADRs. Systemic antimicrobials and caffeine citrate were the drugs that most commonly caused ADRs. According to the ADR Severity Assessment Scale, 41% were mild, 42% were moderate and 17% were severe. Of the ADRs identified, 11% were classified as 'certain' by the Naranjo method and 20% were classified as 'defined' by the Karch and Lasagna modified algorithm. Most of the ADRs detected were related to feed intolerance, phlebitis and tachycardia. Most were acute (73%) and lasted between 1 and 7 days (39%). After the occurrence of an ADR, it was necessary to initiate specific treatment in 44 cases, discontinue the drugs involved in 30 cases, and reduce the drug dose in another 30 cases. An association was shown between the number of drugs prescribed and ADR onset. CONCLUSIONS: There is a high incidence of ADRs in hospitalised newborns, which increases with the number of prescriptions.

Risk of cerebrovascular accident associated with use of antipsychotics: population-based case-control study.

OBJECTIVES: To explore the association between use of antipsychotics and risk of cerebrovascular accident (CVA) in individuals with dementia aged 65 and older. DESIGN: Population-based case-control study. SETTING: UK-based electronic primary care records in the General Practice Research Database (GPRD). PARTICIPANTS: Individuals with dementia aged 65 and older registered in the database between January 1, 1995, and June 22, 2007. MEASUREMENTS: Odds ratio (OR) of CVA in users versus nonusers of antipsychotics (typical or atypical) and in users of typical versus atypical antipsychotics. Multivariate analyses were performed using logistic regression models to adjust for potential confounders: demographic variables, comorbidity, and concomitant treatments. RESULTS: After adjusting for confounding variables, the OR of CVA associated with use of only typical antipsychotics versus no antipsychotics in individuals with dementia aged 65 and older was 1.16 (95% confidence interval (CI)=1.07-1.27) and for use of only atypical antipsychotics versus no antipsychotics was 0.62 (95% CI=0.53-0.72). In the comparison of typical versus atypical antipsychotics, the OR was 1.83 (95% CI=1.57-2.14). CONCLUSION: No reasons were found to question the cerebrovascular safety of atypical antipsychotics in older adults with dementia. The typical antipsychotics appear to be associated with a higher risk of CVA, although the risk disappears after use is discontinued.

Truncated area under the urinary excretion rate curve in the evaluation of alendronate bioequivalence after a single dose in healthy volunteers.

This study was designed to evaluate the bioequivalence of two formulations of alendronate (CAS 121268-17-5) 70 mg (test formulation, alendronate 70 mg tablets, vs. the reference formulation) in 80 healthy volunteers under fasting conditions. The trial followed an open, randomized, crossover design with a washout period of 28 days. Urine samples were collected up to 48 h post-dose, and the concentrations of alendronate were determined by HPLC. The mean Ae(0-48) was (mean +/- SD) 152.15 +/- 136.09 microg for the reference formulation and 150.37 +/- 126.20 microg for the test formulation, while the mean Rmax was 53.33 +/- 41.53 microg/h and 55.85 +/- 49.57 microg/h, respectively. No significant differences in pharmacokinetic parameters between the two formulations were found. The 90% confidence interval for the ratios of Ae(0-48) and Rmax of alendronate were within the acceptance range for bioequivalence trials. The results of the present study suggest that the test formulation is bioequivalent to the reference formulation. The analyses of truncated AURC to shorter times showed similar values, which were within the range of bioequivalence.

Effect of drug-test interactions on length of hospital stay.

PURPOSE: To evaluate the impact of drug-laboratory test interactions on the length of stay of hospitalised patients. METHODS: Observational study of 404 discharges from the Internal Medicine Services of a tertiary hospital. Databases with information on general data, medication and tests performed were linked with the potential interactions described in the literature. This revealed the potential interactions between drugs and laboratory tests (PIDL) in each patient. Several linear regression models, adjusted for confounders, were performed to test the effect of both the number of PIDL and their influence on tests results (false positive/negative) on the length of stay. RESULTS: A total of 19 741 PIDL were detected; 5954 could give rise to potential false positive (PFP) results and 8442 to potential false negative (PFN) ones. Each PFP was related to an increase of 0.051 days in stay duration (CI95% 0.001-0.102) and each PFN to 0.045 days (CI95% 0.008-0.081). Globally, 303 and 380 days of hospitalisation could be attributed to false positives and false negatives, which could account for 9.8% of the total stay of these patients. CONCLUSIONS: These results show that the interactions between drugs and laboratory tests produce a statistically and clinically significant increase in the duration of hospital stay.

A health system program to reduce work disability related to musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders (MSDs) are a frequent cause of work disability, accounting for productivity losses in industrialized societies equivalent to 1.3% of the U.S. gross national product. OBJECTIVE: To evaluate whether a population-based clinical program offered to patients with recent-onset work disability caused by MSDs is cost-effective. DESIGN: Randomized, controlled intervention study. The inclusion and follow-up periods each lasted 12 months. SETTING: Three health districts in Madrid, Spain. PATIENTS: All patients with MSD-related temporary work disability in 1998 and 1999. INTERVENTION: The control group received standard primary care management, with referral to specialized care if needed. The intervention group received a specific program, administered by rheumatologists, in which care was delivered during regular visits and included 3 main elements: education, protocol-based clinical management, and administrative duties. MEASUREMENTS: Efficacy variables were 1) days of temporary work disability and 2) number of patients with permanent work disability. All analyses were done on an intention-to-treat basis. RESULTS: 1,077 patients were included in the study, 7805 in the control group and 5272 in the intervention group, generating 16,297 episodes of MSD-related temporary work disability. These episodes were shorter in the intervention group than in the control group (mean, 26 days compared with 41 days; P < 0.001), and the groups had similar numbers of episodes per patient. Fewer patients received long-term disability compensation in the intervention group (n = 38 [0.7%]) than in the control group (n = 99 [1.3%]) (P < 0.005). Direct and indirect costs were lower in the intervention group than in the control group. To save 1 day of temporary work disability, 6.00 dollars had to be invested in the program. Each dollar invested generated a benefit of 11.00 dollars. The program's net benefit was in excess of 5 million dollars. LIMITATIONS: The study was unblinded. CONCLUSIONS: Implementation of the program, offered to the general population, improves short- and long-term work disability outcomes and is cost-effective.

Bioequivalence study of two different tablet formulations of carvedilol in healthy volunteers.

OBJECTIVE: The aim of this study was to compare the extent and rate of absorption of two different carvedilol (CAS 72956-09-3) tablet formulations: 25 mg tablets, as the test formulation and the reference innovator product (25 mg tablets). METHODS: This study was designed as a single-dose, open-label, randomised, with a two-period and two-sequence crossover design, with blind determination of drug plasma concentration and a minimum 7-day washout period. Twenty-four healthy volunteers of both sexes were randomly assigned to treatment sequences. Carvedilol concentrations were determined in plasma samples obtained over a 24-h interval: baseline (pre-administration) and at 14 different times within the 24 h after administration. The analytical method, which used HPLC coupled with a MS/MS detector, was duly validated and the analytical assay was performed in compliance with Good Laboratory Practice (GLP). The limit of quantification (LOQ) was 0.50 ng/mL. Pharmacokinetic parameters representing the extent and/or rate of absorption (AUCinf, AUClast, and Cmax) were obtained. As secondary objective the tolerability of both formulations was also evaluated. RESULTS: The geometric mean of the test/reference formulations individual percent ratio was 98.14 % for AUCinf, 98.44 % for AUClast and 98.39 % for Cmax. The 90 % CI for the geometric mean of the individual ratio test/references formulations was 95.13 to 101.24 % for AUCinf, 95.23 to 101.76 % for AUClast, and 88.26 to 109.67 % for Cmax. CONCLUSIONS: The 90 % CI values obtained for AUCinf, AUClast, and Cmax are within the interval proposed by the EMEA/CPMP and the FDA as bioequivalence acceptance criteria, and consequently it can be conclude that the test formulation is bioequivalent with the reference formulation both in terms of rate and extent of absorption after single dose administration. The results from a previous pilot study allowed an optimal design for this trial.

Food-drug interactions in the summary of product characteristics of proprietary medicinal products.

BACKGROUND: Food-drug interactions can produce negative effects in the safety and efficacy of drug therapy, as well as in the nutritional status of the patient. However, the data commonly provided to the prescriber about possible nutrient-pharmacological compound interactions and the recommendations for their prevention are often scarce. The summary of product characteristics (SmPC) of a proprietary medicinal product, as authorised by the health authorities in Europe, is usually the main source of information for the health professional. Therefore, the SmPC can be a useful tool to prevent or reduce food-drug interactions and, as a consequence, improve the therapeutical approach. OBJECTIVE: The aim of this study was to assess the information about food-drug interactions with potential clinical relevance as it is described in the SmPCs of the authorised medicinal products in a European Union country (Spain). METHODS: A bibliographical search of food-drug interactions, including nutrients and alcohol, was carried out. The adequate information to be included in the SmPC was defined in accordance with the European Recommendations in this field. The SmPCs of the medicinal products containing selected active substances were examined with emphasis on food-drug interactions. RESULTS: It was found that, frequently, the information concerning food-drug interactions as is mentioned in the SmPC of the authorised medicinal products in Spain does not fulfil the current recommendations, both in quantity and quality. Indeed, the available data reveal that the food-drug information is only mentioned in 72.7% of all SmPC where it should be and it was only found in the specific section for interactions in 36.0% of all cases. The description and agreement with recommendations for each SmPC item ranged between 4.2% and 36.0% and between 31.8% and 49.0%, respectively. Some related factors, such as the clinical relevance of the interaction, the existence of an authorised SmPC and the registration procedure followed, influence the information characteristics concerning food-drug interactions. CONCLUSION: The SmPC is a suboptimal source of information for food-drug interactions.

Bioequivalence study of two formulations of enalapril, at a single oral dose of 20 mg (tablets): A randomized, two-way, open-label, crossover study in healthy volunteers.

BACKGROUND: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an angiotensin-converting enzyme inhibitor indicated in the management of essential and renovascular hypertension, and in the treatment of congestive heart failure and in asymptomatic patients with left ventricular dysfunction and an ejection fraction of ≥35%. Enalapril has little pharmacologic activity until hydrolyzed in vivo to enalaprilat. OBJECTIVE: The aim of the present study was to compare the bioavailability and tolerability of 2 commercial brands (test and reference formulations) of enalapril tablets (20 mg), described as the rate and extent of absorption of the active moiety, to assess their bioequivalence. METHODS: This single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit, Hospital Clínico San Carlos (Madrid, Spain). Subjects were randomized to receive (under fasting conditions) either the test or reference formulation of enalapril (20-mg tablet) at study period 1 and the opposite formulation at study period 2. Study periods were separated by a washout period of at least 7 days. During each study period, 15 plasma extractions were made to determine enalapril and enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK) properties (maximal plasma drug concentration [Cmax], time to Cmax [Tmax], area under the plasma concentration-time curve [AUC] to the last measurable concentration [AUCt], AUC from time 0 to infinity [AUC0-∞], mean residence time, and elimination half-life [tl2]) of both. Physical examination, subject interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were used to assess tolerability. RESULTS: Twenty-four subjects were included in the study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]). Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK and statistical analyses included results from 23 subjects. No statistically significant sequence or period effect was found. Tmax was not statistically different between the 2 formulations, and the 90% CI calculated for Tmax for the difference of the medians was within the predefined range. The 90% CIs of the logarithmically transformed concentration-derived parameters (Cmax AUCt, and AUC0-∞) also were within the predefined range; thus, the 2 formulations are considered bioequivalent. For both formulations, systolic and diastolic BPs showed significant reductions compared with baseline values (P < 0.05). Seven adverse effects were recorded, all of them transient and none of severe intensity. CONCLUSIONS: In this study of 2 commercial brands (test and reference formulations) of enalapril in healthy subjects, designed and conducted under Good Clinical Practice guidelines, a similar rate and extent of absorption for both formulations were found to be bioequivalent. Both formulations produced a significant decrease in BP values and were generally well tolerated.

[Association between non-steroid antiinflammatory drugs intake and decompensation of heart failure]. / Asociación entre consumo de antiinflamatorios no esteroideos e insuficiencia cardíaca congestiva.

BACKGROUND AND OBJECTIVE: Our purpose was to estimate the association between the intake of non-steriodal anti-inflammatory drugs (NSAIDs) and hospitalization due to heart failure (HF) and to assess the effect of selective COX-2 inhibitors. PATIENTS AND METHOD: This was a case-control study, including 982 patients with HF, and 788 controls, with a history of HF who were hospitalized in 10 hospitals of the community of Madrid. RESULTS: The use of NSAIDs (other than aspirine at low doses) was associated with an increase in the risk of hospitalization due to HF (OR crude = 1.59; 95% interval confidence, 1.20-2.09; OR adjusted, 1.40; 95% interval confidence, 1.03-1.90). CONCLUSIONS: Intake of NSAIDs is associated with an increased risk of hospitalization due to HF, in susceptible patients.