Risk of Potential Drug-Drug Interactions among Brazilian Elderly A Population-Based, Cross-Sectional Study

Background: Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives: To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods: A population-based cross-sectional study was carried out involving 2143 elderly (aged 60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results: Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >= 75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions: Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children`s growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling. The trials were registered at www.clinicaltrials.gov as #NCT00598481 and #NCT00599781. (Blood. 2009; 114: 3216-3226)

Characteristics of a large population of patients with refractory epilepsy attending tertiary referral centers in Italy

P>The characteristics of 1,124 consecutive adults and children with refractory epilepsy attending 11 tertiary referral centers in Italy were investigated at enrollment into a prospective observational study. Among 933 adults (age 16-86 years), the most common syndromes were symptomatic (43.7%) and cryptogenic (39.0%) focal epilepsies, followed by idiopathic (8.1%) and cryptogenic/symptomatic generalized (6.2%) epilepsies. The most common syndrome among 191 children was symptomatic focal epilepsy (35.1%), followed by cryptogenic focal (18.8%), cryptogenic/symptomatic generalized (18.3%), undetermined whether focal or generalized (16.8%), and idiopathic generalized (7.3%). Primarily and secondarily generalized tonic-clonic seizures were reported in 27.8% of adults and 16.8% of children. The most commonly reported etiologies were mesial temporal sclerosis (8.0%) and disorders of cortical development (6.2%) in adults, and disorders of cortical development (14.7%) and nonprogressive encephalopathies (6.8%) in children. More than three-fourths of subjects in both age groups were on antiepileptic drug (AED) polytherapy.

A Novel Approach to Intraoral Mandibular Nerve Anesthesia: Changing Reference Planes in the Gow-Gates Block Technique

Purpose: The Gow-Gates technique is said to have several advantages over traditional techniques to achieve mandibular nerve anesthesia; however, its routine use is quite limited, mainly due to complications during visual alignment of reference landmarks. The purpose of this study was to verify the validity and accuracy of a new method to reach the injection site. Material and Methods: Fifteen magnetic resonance images were captured. Distances from the ideal injection point in the condylar neck (puncture ideal) to the injection points located in the a and 0 plane intersection (Puncture Gow-Gates and puncture modified) were measured and compared. Results: Positive and significant (P <= .003) Pearson correlations between landmarks and injection points confirmed the validity of the modified technique. Paired t test showed that the segment line puncture ideal-puncture modified, 5.17 mm, was 3 times shorter (P < .001) than the segment line puncture ideal-puncture Gow-Gates, 17.91 mm. As calculated by linear regression, establishing the injection point of the modified technique depended only on the anteroposterior and lateromedial condyle positions. Conclusions: The modified technique proved to be valid and precise and has a determined and an effective injection site. (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:2609-2616, 2009

Low-Fluoride Acidic Dentifrice: A Randomized Clinical Trial in a Fluoridated Area

Background: Low-fluoride dentifrices have been suggested as alternatives to reduce dental fluorosis risk, but there is no consensus regarding their clinical effectiveness, which has been suggested to be increased when their pH is acidic. Aims: This single-blind randomized clinical trial evaluated the caries increment during the use of a low-fluoride acidic liquid dentifrice. Methods: Four-year-old schoolchildren (n = 1,402) living in a fluoridated area (0.6-0.8 ppm F) were randomly allocated to 4 groups differing according to the type of dentifrice used over a 20-month period. Group 1 (n = 345): liquid dentifrice, 1,100 ppm F, pH 4.5. Group 2 (n = 343): liquid dentifrice, 1,100 ppm F, pH 7.0. Group 3 (n = 354): liquid dentifrice, 550 ppm F, pH 4.5. Group 4 (n = 360): toothpaste, 1,100 ppm F, pH 7.0. At baseline and after 20 months, clinical examinations were conducted (dmfs index) and caries increment was calculated. Data were analysed by GLM procedure using classrooms (cluster) as unit of analysis (p < 0.05). Results: The mean +/- SD (95% CI) net increments found were as follows. Group 1: 2.06 +/- 2.38 (1.8-2.3); group 2: 2.08 +/- 2.87 (1.7-2.4); group 3: 2.05 +/- 2.79 (1.7-2.4), and group 4: 2.08 +/- 2.34 (1.8-2.4). No significant differences were detected among the groups. Conclusion: In a population with high caries risk living in a fluoridated area, as the selected sample, and according to the present protocol, the low-fluoride acidic liquid dentifrice seems to lead to similar caries progression rates as conventional 1,100 ppm F toothpaste. Copyright (C) 2010 S. Karger AG, Basel

Should watchful waiting be used more often for acute otitis media?

RECENT ANXIETY about the treatment of acute otitis media has been precipitated by a resistance to antibiotics by the common pathogens that can cause this infection.1, 2 The medical profession is facing an increasingly impotent option in the form of antibiotics, prompting physicians around the world to consider alternatives. In this issue of the ARCHIVES, Pichichero and Poole3 have undertaken a comprehensive study involving pediatricians and otorhinologists. The objectives were to assess their recognition of the physical findings of acute otitis media and their ability to perform myringotomy. The principal issue is the safety of performing myringotomy in children with acute otitis media. Because this is an office procedure in which a general anesthetic is not administered, the child is strapped to a papoose board and held down. Myringotomy is not without potential serious complications. The superior part of the middle ear cavity contains the ossicles and the chorda tympani branch . . . [Full Text of this Article]

Liver transplantation: current status and future prospects

The enormous progress that has been made in liver transplantation over the past two decades has culminated in survival approaching 90% at 12 months. The success of the procedure combined with the widening spectrum of disease processes deemed amenable to liver transplantation has meant that there are too few donors for those awaiting transplantation. This has extrapolated to many patients having such advanced disease by the time a suitable donor liver is available, that they are almost non-transplantable. The immediate options facing the transplant community are to decrease the number of patients listed or to increase the number of living donor transplants. Alternatives to liver transplantation such as hepatocyte transplantation, gene therapy, xenotransplantation and the bioartificial liver are being sought but, at best, are some way from clinical application. It is anticipated that a number of liver diseases that are indications for liver transplantation at this time will have progression arrested or will be cured by medical therapy in the future.

A decision support system for selecting sanitation systems in developing countries

Due to the socio-economic inhomogeneity of communities in developing countries, the selection of sanitation systems is a complex task. To assist planners and communities in assessing the suitability of alternatives, the decision support system SANEX™ was developed. SANEX™ evaluates alternatives in two steps. First, Conjunctive Elimination, based on 20 mainly technical criteria, is used to screen feasible alternatives. Subsequently, a model derived from Multiattribute Utility Technique (MAUT) uses technical, socio-cultural and institutional criteria to compare the remaining alternatives with regard to their implementability and sustainability. This paper presents the SANEX™ algorithm, examples of its application in practice, and results obtained from field testing.