Impact of patients' perception of COPD and treatment on adherence and health-related quality of life in real-world: Study in 53 community pharmacies.

BACKGROUND: Patient adherence to treatment in chronic obstructive pulmonary disease (COPD) is essential to optimize disease management. We aimed to assess the impact of patients' perception of their treatment and disease on adherence and Health-Related Quality of Life (HRQL) in patients attending a community pharmacy, where usually subjects have a better condition than those in clinical settings. METHODS: We performed a cross-sectional study of 318 patients with COPD in treatment with inhalers in the last 3 months from 53 community pharmacies. We assessed HRQL with St George's Respiratory Questionnaire (SGRQ). Persistence was assessed from the three previous refills and adherence through the Test of Adherence to Inhalers test. RESULTS: Persistence was achieved by 78.6% of the patients and 58.5% had good adherence. Patients having a multidose DPI and those with MDI showed a 2.8-fold and 4.1-fold increased association, respectively, with intermediate/poor adherence in comparison with those having a single dose DPI. Those patients who did not have knowledge about COPD (aOR 2.106, p = 0.006) and those who thought that the inhaler effectiveness was fair/poor (aOR 2.361, p = 0.006) were more likely to have intermediate/poor adherence. Overall SGRQ score was significantly worse in patients with intermediate/poor adherence (p = 0.036) and in those who thought the inhaler's effectiveness was fair/poor (p < 0.001). CONCLUSIONS: The type of inhaler and patients' knowledge and perceptions of their disease and treatment were associated with good adherence and higher HRQL. Clinicians should promote shared-decision making in the choice of inhaler depending on patients' individual abilities and beliefs.

[Javier Sádaba: A bioethics against suffering]. / Javier Sádaba: una bioética contra el sufrimiento.

The philosopher Javier Sádaba (Portugalete, 1940) is the author of an extensive work in the field of bioethics. It is a procedural bioethics (based on the agreement between the participants, not on absolute truths), casuistry (is based on the analysis of specific problem cases), social (evaluates the context in decision-making), gradual (considers other species, is not "narcissistically human"), and secular (autonomous with respect to religion). Sádaba has also opted for an affirmative bioethics, which seeks to improve the living conditions of humans (in medicine, the quality of life). This is difficult to construct because, for the philosopher, the duty and to establish limits are infinitely easier to elaborate than the specific good and to pursue happiness. In its application to medicine, Sádaba's bioethics focuses on avoiding unnecessary suffering, because suffering does not contribute anything positive and hinders happiness. Likewise, he strives to extract the best of science and open the doors to everything that can bring improvements for the human being, but without ceasing to mention responsibility, because man is capable of the best and the worst. From this perspective, the author is faced with the bioethical issues, leaving the greatest possible margin to freedom of choice.

Impact of changes in pill appearance in the adherence to angiotensin receptor blockers and in the blood pressure levels: a retrospective cohort study.

OBJECTIVE: To assess the level of adherence to angiotensin receptor blockers (ARBs) in patients regularly attending a community pharmacy and the influence of a change in patients' adherence to pharmacological treatment. DESIGN: Retrospective cohort study of a random sample of consecutive patients collecting their medication. SETTING: 40 community pharmacies in Alicante (Southeast Spain). PARTICIPANTS: 602 consecutive ≥18 years old patients following treatment with ARBs at least 3 previous refills were included. MAIN OUTCOME MEASURES: Prevalence of uncontrolled blood pressure (BP) and adherence to prescribed pharmacological treatment (measured through both the Batalla and the Morisky-Green tests). A multivariate Poisson regression model was used to estimate the adjusted risk ratio (RRa) for non-adherence to pharmacological treatment by the presence of a change in patient's adherence and other significant variables. RESULTS: 161/602 (13.7%) patients presented uncontrolled BP. According to the Morisky test, 410/602 (68.2%) patients were considered adherent to pharmacological treatment and 231/602 (38.4%) patients according to the Batalla test. According to the Morisky-Green test, in the multivariable analysis, patients with a previous change in pill appearance were less likely to be adherent than those patients with no change in their pharmacological treatment (RRa 0.45; CI 95% 0.22 to 0.90; p=0.024). Systolic BP was higher in patients with a change in pill appearance in the previous 3 refills (median BP 142 mm Hg; IQR 136-148) than in those who did not have a change (median BP 127 mm Hg; IQR 118-135; p<0.001). CONCLUSIONS: There was a low percentage of adherence and nearly 15% of uncontrolled BP in patients who regularly collected their medication. Switching between pills of different appearances was associated with lower patient adherence to pharmacological treatment and a higher uncontrolled BP than no change in pharmacological treatment or change only in package but not in pill appearance.

Recurrent infection in the left thumb.

INTRODUCTION: Infections of the hand may be associated with lymphangitis and lymphadenitis. In most cases, bacterial infections are responsible but these may be also due to viral infections. MATERIAL AND METHODS: We describe a clinical case of a recurrent infection in the left thumb of a health male. Bacterial and viral cultures were performed. RESULTS: Herpes simplex virus (HSV) type 2 was isolated on viral culture and on direct fluorescent antibody testing; so, the final diagnosis was herpetic whitlow. CONCLUSIONS: Herpetic whitlow should be considered in cases of recurrent finger infections.

[Conflictive patients in the emergency room: Definition, classification and ethical aspects]. / Paciente conflictivo en urgencias: definición, tipología y aspectos éticos.

A conflictive patient is one who provokes a problem (a conflict) by their attitude or behavior for the physician. Ethical conflicts in emergency care are common and many of them occur with these patients. Among the most common types of patients who generate personal conflicts with health professionals are overly demanding patients, those who refuse medical interventions, those who are aggressive, litigators, excessively-recurrent users of the heath system and those who go to the emergency room without an urgent condition. A patient may include several of these profiles ("mixed" patient). When they appear, the approach should be, if possible, by a team, establishing a deliberative process. If there is doubt and when possible, the ethics committee of the institution should be consulted, seeking the protocols, this best being institutional, on the subject. After that, if the decision is difficult, support must be sought from the emergency staff and even management. The whole process should be reflected in the clinical history. Specific education in bioethics and communication skills can be of great help to minimize and cope better with long-term conflicts.

[Toxic epidermal necrolysis induced by phenytoin and whole brain radiotherapy]. / Necrolisis epidérmica tóxica inducida por fenitoína y radioterapia holocraneal.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) have been associated with some drugs, particularly anticonvulsants such as phenytoin. Some authors have pointed out an increased risk of TEN/SJS when phenytoin is associated with whole brain radiotherapy. We report a patient diagnosed with breast adenocarcinoma and brain metastases that was on treatment with phenytoin and, shortly after receiving whole brain radiotherapy, developed toxic epidermal necrolysis.

Modelling intestinal absorption of salbutamol sulphate in rats.

The objective was to develop a semiphysiological population pharmacokinetic model that describes the complex salbutamol sulphate absorption in rat small intestine. In situ techniques were used to characterize the salbutamol sulphate absorption at different concentrations (range: 0.15-18 mM). Salbutamol sulphate at concentration of 0.29 mM was administered in presence of verapamil (10 and 20 mM), grapefruit juice and sodium azide (NaN3) (0.3, 3 and 6 mM). Different pharmacokinetic models were fitted to the dataset using NONMEM. Parametric and non-parametric bootstrap analyses were employed as internal model evaluation techniques. The validated model suggested instantaneous equilibrium between salbutamol sulphate concentrations in lumen and enterocyte, and the salbutamol sulphate absorption was best described by a simultaneous passive diffusion (ka = 0.636 h(-1)) and active absorption (VMax = 0.726 mM/h, Km = 0.540 mM) processes from intestinal lumen to enterocyte, together with an active capacity-limited P-gp efflux (V'max = 0.678 mM/h, K'm = 0.357 mM) from enterocyte to intestinal lumen. The extent of salbutamol sulphate absorption in rat small intestine can be improved by NaN3, grapefruit juice and verapamil.

Lipid metabolism and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: role of cholesteryl ester transfer protein and paraoxonase/arylesterase.

Plasma lipid metabolic and transfer processes have recently been suggested to play an important role in the development of early restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA); in particular, the common variants of genes for cholesteryl ester transfer protein (CETP) and paraoxonase (PONA) have been implicated. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The CETP-TaqIB (intron 1), CETP-MspI (intron 8), and PONA-AlwI (exon 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 ("cases") had developed restenosis (as defined by > 50% loss of lumen compared with immediate postprocedure results) at repeat angiography at 6 months post PTCA. Selected frequencies for CETP B1 and B2 alleles (absence/presence of TaqIB site) were 0.65 and 0.35 (cases) and 0.65 and 0.35 (controls), respectively; frequencies for CETP M1 and M2 alleles (absence/presence of MspI site) were 0.20 and 0.80 (cases), 0.21 and 0.79 (controls), respectively; frequencies for PONA A and B alleles (absence/presence of AlwI site) were 0.73 and 0.27 (cases), 0.72 and 0.28 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for gene-gene interaction, or an association between genotype and restenosis or degree of lumen loss (adjusted for covariates). Our data, collected in the largest study of its kind so far, indicate that the common variants for CETP and PONA are not associated with incidence of restenosis after PTCA, and are therefore not useful markers for risk assessment.

Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease.

The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.

Mesenteric tuberculosis with jejunal infiltration.

A 69-year-old female was admitted to our hospital because of asthenia, anorexia and 20 kg weight loss. An ultrasound study and computerized tomography (CT) imaging revealed a mesenteric mass and laparotomy was performed. The diagnosis was mesenteric tuberculosis with jejunal involvement. This represents an atypical onset of tuberculosis in a non-immunosuppressed patient.

Ace D/I polymorphism and incidence of post-PTCA restenosis: a prospective, angiography-based evaluation.

Early restenosis is the major complication of percutaneous transluminal coronary angioplasty (PTCA), occurring in approximately 30% of all initially successful procedures. The D/I polymorphism of the ACE gene, which has variably been reported to represent a risk factor for manifestations of ischemic heart disease, has recently been implicated in the pathophysiology of restenosis after PTCA by some investigators but not by others. All studies conducted thus far involved relatively small sample sizes. We investigated the possible association of ACE D/I genotype and post-PTCA restenosis in a large, prospective sample of patients followed by quantitative coronary angiography. The ACE D/I gene polymorphism was characterized in a cohort of 779 patients, of whom 342 (cases) had developed restenosis (as defined by >50% loss of lumen compared with immediate postprocedure results) at repeat quantitative coronary angiography at 6 months after PTCA. Allele frequencies for the ACE D and I: alleles were 0.58 and 0.42 in cases and 0.58 and 0.42 in control subjects. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and restenosis or degree of lumen loss. The data from this largest study of its kind conducted so far provide no evidence for an association of the ACE D/I allelic polymorphism with incidence of restenosis after PTCA. On the basis of the power of this study, we conclude that in a general population, the ACE D/I polymorphism is not a useful marker to assess risk of post-PTCA restenosis.

[Leukocytoclastic vasculitis associated with ticlopidine]. / Vasculitis leucocitoclástica en relación con ticlopidina.

In the last five years the combination of ticlopidine plus aspirin has been the treatment of choice to avoid thrombi formation after the implantation of intracoronary stents. The adverse effects observed include the appearance of a maculopapulous, pruritic, painless, cutaneous rash. We present the case of a patient who developed leucocytoclastic vasculitis associated with the administration of ticlopidine.

Circulating monocytes in patients with diabetes mellitus, arterial disease, and increased CD14 expression.

Low serum concentrations of high-density lipoprotein (HDL) cholesterol and elevated levels of acute-phase reactans are frequently found in patients with non-insulin-dependent diabetes mellitus (NIDDM) and cardiovascular disease. Changes in the phenotype of circulating monocytes have been reported with both of these circumstances in nondiabetic subjects. In the present study, we explored the possibility that similar changes may occur in circulating monocytes of patients with NIDDM and arterial disease. Two groups of subjects with NIDDM were studied: patients with cardiovascular disease (n = 25) were compared with a group without cardiovascular disease (n = 26); both groups were age- and sex-matched, had the same length of diabetes duration, and degree of glycemic control. Healthy nondiabetic volunteers of comparable age and sex (n = 35) formed the control group. There was no significant difference in the numbers of the CD14+/CD16+ monocyte subpopulations between the 3 groups. However, a significant graded increase of the mCD14 intensity expression values was observed among the groups, with the highest levels in patients with NIDDM patients and the lowest in nondiabetic subjects. The serum C-reactive protein concentrations were significantly higher in the group with arterial disease compared with those without arterial disease or healthy controls. In the group of patients as a whole, relative mCD14 intensity expression was significantly correlated with HDL cholesterol levels (inversely) and with serum concentrations of C-reactive protein. Serum HDL cholesterol levels and the C-reactive protein concentrations were also significantly correlated. We concluded that the increased mCD14 intensity expression on circulating monocytes may be an important contributor to the increased inflammatory response observed in patients with NIDDM and arterial disease, and eventually, to atherogenesis.

Pulmonary tuberculosis presenting with cutaneous leukocytoclastic vasculitis.

This case report deals with a rare association: tuberculosis and cutaneous leukocytoclastic vasculitis. The patient was a 36-year-old man with no significant past medical problems. He presented with a palpable purpura on both legs, low-grade fever, cough and expectoration, progressive dyspnea due to a massive left pleural effusion and a symmetric swelling on his ankles and wrists. Skin biopsy yielded a histological diagnosis of leukocytoclastic vasculitis and the primary diagnosis was only achieved after performing a pleural biopsy, which unequivocally showed the presence of Mycobacterium tuberculosis. This case shares many features with the few cases already reported in the medical literature. Possible pathogenic mechanisms are reviewed and discussed in detail.

[Invasive aspergillosis in patients with human immunodeficiency virus infection diagnosed by necropsy: the contribution of 4 cases and review of the literature]. / Aspergilosis invasiva en pacientes infectados por el virus de la inmunodeficiencia humana diagnosticados por necropsia: aportación de 4 casos y revisión de la bibliografía.

BACKGROUND: Invasive aspergillosis is an infrequent clinicopathological entity which is difficult to diagnose (since it requires tissue samples, normally of the lung where the pathogenic effect of the fungi may be seen) and thus an important number of cases are not found until necropsy. In patients with human immunodeficiency virus (HIV) infection the real incidence has not been clearly defined and may be higher than reported. MATERIAL AND METHODS: We herein present a series of necropsy reviews performed over a five year period (January 1993 to December 1997) in the Hospital Universitario San Carlos in Madrid (Spain) in patients with HIV infection. In the patients who presented invasive aspergillosis a collection protocol of clinical, analytical and radiologic data was undertaken. RESULTS: Over this period necropsic studies were performed in 23 patients with HIV infection. Of these 4 (17.3%) presented invasive aspergillosis; 3 with disseminated involvement. Premortem diagnosis was not performed in any of the cases. The risk factors included: 3 had a CD4 count of less than 50, two were receiving glucocorticoids and only 1 had severe neutropenia. In 2 another opportunistic lung infection was also observed. CONCLUSIONS: Invasive aspergillosis is an entity witch is found on autopsy with relative frequency in patients with HIV infection with severe immunodepresion. Other opportunistic infections may also coincide and it may not be associated with neutropenia, glucocorticoid treatment, which are considered as classical risk factors for invasive aspergillosis.