Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. METHODS: A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). RESULTS: Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. CONCLUSIONS: Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4.

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Mesalazine-associated tubulo-interstitial nephritis in inflammatory bowel disease.

The 5-aminosalicylic acid (5-ASA) is currently the treatment of choice for patients with inflammatory bowel disease. It can be administered as sulfasalazine (5-ASA + sulfapyridine), mesalazine (5-ASA + resins or gels) and olsalazine (two molecules of 5-ASA). The recent trend has been to use formulations without sulfapyridine since they produce less side-effects although some cases of nephrotoxicity have been described. We report the case of a young female with Crohn's disease treated with mesalazine (400 mg every 8 hours) over a period of 12 months who developed acute interstitial nephritis. The characteristic features of renal function impairment were an insidious onset with non-specific laboratory data and progression towards a chronic state which partially improved with steroid treatment. In summary, it is important to bear this possibility in mind when confronted by any renal impairment which cannot be related to a relapse of inflammatory bowel disease. Renal function should be monitored routinely in patients receiving mesalazine at least during the first year of treatment and annually thereafter.

[Absence of benefit with triple antiaggregation in acute non persistent ST segment elevation myocardial infarction in patients not subjected to early interventionism]. / Ausencia de beneficio con triple antiagregación en el síndrome coronario agudo sin elevación persistente del segmento ST, en pacientes no sometidos a intervencionismo precoz.

OBJECTIVE: To assess the efficacy and safety of a treatment with clopidogrel when associated or not to the treatment with tirofiban and aspirin for high-risk non-ST segment elevation myocardial infarction (non-STEMI), without early angioplasty. SETTING: Intensive Care and Coronary Unit (ICCU), in a center with no Hemodynamic Laboratory. DESIGN: Non randomized clinical trial. PARTICIPANTS: One hundred and twenty-three patients admitted with the diagnosis of high-risk non-STEMI, defined as patients with chest pain and one of the following: ST segment depression or transient elevation or an elevation in cardiac troponin I (TropIc). INTERVENTIONS: We included patients admitted in a 24-month period. During the first 12-month period, the patients received tirofiban and clopidogrel (group A). In the second one, clopidogrel was not administered (group B). Urgent cardiac catheterism was requested if recurrent ischemic chest pain with ST segment changes, left ventricular failure or hemodynamic instability were present. PRIMARY VARIABLES: A composite of recurrent ischemic chest pain with ST segment changes or death during ICCU admission was evaluated as an efficacy variable. A variable of safety was defined as the occurrence of intracranial or gastrointestinal bleeding, or any hemorrhagic event accompanied by a drop of at least 3 g/dl of hemoglobin. The rate of urgent cardiac catheterisms was recorded. RESULTS: Neither the rate of the efficacy variable (19.6 % in group A and 19.4% in group B; p = 0.97), nor the rate of the safety variable (3.5% and 2.9% of patients in groups A and B, p = 1) showed statistically significant difference. There was no statistically significant difference in the rate of urgent cardiac catheterism (19.6% in group A and 13.4% in group B; p = 0.35). CONCLUSIONS: In the early course of high-risk non-STEMI with a conservative management strategy, the addition of clopidogrel to tirofiban does not change the rate of ischemic events, death, need of urgent catheterism or hemorrhagic events.

Critical role of ribavirin for the achievement of early virological response to HCV therapy in HCV/HIV-coinfected patients.

The response to hepatitis C virus (HCV) therapy seems to be lower in HCV/HIV-coinfected patients than in HCV-monoinfected individuals. Given that most pivotal trials conducted in coinfected patients have used the combination of pegylated interferon (pegIFN) along with fixed low doses (800 mg/day) of ribavirin (RBV), it is unclear whether HIV itself and/or suboptimal RBV exposure could explain this poorer outcome. Two well-defined end points of early virological response were evaluated in Peginterferon Ribavirina España Coinfección (PRESCO), a multicentre trial in which the combination of pegIFN plus RBV (1000 mg if body weight <75 kg and 1200 mg if >75 kg) was prescribed to coinfected patients. For comparisons, we used unpublished data from early kinetics in two other large trials, one performed in HIV-negative patients [Pegasys International Study Group (PISG)] in which RBV 1000-1200 mg/day was used and another [AIDS Pegasys Ribavirin Coinfection Trial (APRICOT)] in which HIV-positive patients received fixed low RBV doses (800 mg/day). A total of 348 HCV/HIV-coinfected patients from the PRESCO trial were analysed as well as all patients treated with pegIFN plus RBV, who completed 12 weeks of therapy in the comparative studies (435 in PISG and 268 in APRICOT). Negative serum HCV-RNA at week 4 (which has the highest positive predictive value of sustained virological response, SVR) was attained in 33.3%, 31.2% and 13% of treated patients with HCV genotype 1, respectively, in PRESCO, PISG and APRICOT. For HCV genotypes 2/3, responses were 83.7%, 84.2% and 37%, respectively. A decline lower than 2 log(10) at week 12 (which has the highest negative predictive value of SVR) was seen in 25.5%, 19.5% and 37% of HCV genotype-1-infected patients, and in 2.1%, 2.9% and 12% of genotypes-2/3-infected patients, respectively. Prescription of high RBV doses enhances the early virological response to HCV therapy in HCV/HIV-coinfected patients, with results approaching those seen in HCV-monoinfected patients.

[Sedoanalgesia with remifentanil in definitive pacemaker implant]. / Sedoanalgesia con remifentanilo en el implante de marcapasos definitivo.

OBJECTIVE: Describe the use of remifentanil in definitive pacemaker implant. DESIGN: Prospective, observational study. SCOPE: Intensive Care Unit of two general hospitals. PATIENTS: Ninety-four patients subjected to DPM implant under sedation with remifentanil. INTERVENTIONS: The protocol for DPM implant was conducted: premedication with metoclopramide, remifentanil perfusion (20 micro g/ml), local infiltration with mepivacaine 2%, administration of magnesium metamizole at the end of the implant and posterior discontinuation of remifentanil. Remifentanil perfusion was initiated at 2 micro g/minute, increasing it until reaching a sedation grade 2-3 on the Ramsay scale, with a maximum of 6 micro g/minute. MAIN ENDPOINTS: Time needed to reach the desired sedation grade and duration of sedation, maximum dose of remifentanil necessary, frequency that another sedation was needed and of adverse events were recorded. Continuous quantitative endpoints were expressed as mean +/- SD. RESULTS: A sedation grade 2-3 was achieved with a perfusion rhythm of 3.6 +/- 1.4 micro g/min, in 20 +/- 22 minutes. In 89 patients (94.6%), the implant was performed only with remifentanil. Frequency of adverse events were nauseas/vomiting 21.3%, hypotension 5.3% and respiratory depression 1%. Remifentanil perfusion was discontinued in 3 patients (3.2%) due to appearance of adverse events. Another sedoanalgesic was used in 2 patients (2.1%). CONCLUSIONS: Remifentanil is useful in the implant of DPM as a sedoanalgesia method. Serious undesired effects are rare. Future studies are necessary to completely establish its effectiveness and safety in these types of procedures.

Programa de comunicación a distancia. Elaboración de indicadores cuali-cuantitativos para su evaluación / Outreach education program. Development of qualitative and quantitative assessment markers.

La Oficina de Comunicación a distancia (OCD) es una estructura creada en 1997 en el Hospital de Pediatría Juan P. Garrahan, con el objetivo de responder consultas a distancia y facilitar el seguimiento de pacientes, con la intención de evitar los traslados innecesarios. Ha dado respuesta a más de 25000 consultas. Actualmente, en el marco del Programa de Comunicación a Distancia (PCD), funcionan 88 OCD distribuidas en 12 de las 23 provincias argentinas. Se presentan resultados sobre una muestra de 148 consultas realizadas al Hospital Garrahan desde 6 provincias, que participaron de un estudio de tipo descriptivo, retrospectivo, cuali-cuantitativo. Éste permitió formular nuevas formas de registro de la tarea y elaborar indicadores cualicuantitativos para evaluar el PCD: consultas, motivo de consulta, tipo de paciente consultado, necesidad de la consulta, duración de la enfermedad al momento de la consulta, derivación sugerida, tiempo de respuesta. Se analizó el número de consultas y las sugerencias de derivación, mostrando las primeras un progresivo y significativo incremento desde la implementación del PCD. Con relación a los motivos de consulta, 84% correspondió a definición de diagnóstico y tratamiento, 16% a motivos de seguimiento e intercurrencias. 62% presentaba patologías crónicas. 95% de los pacientes fueron definidos como complejos. 79% correspondió a consultas definidas como imprescindibles. La derivación fue sugerida en el 54% de las consultas. La mediana del tiempo de respuesta fue de 48 horas. El bajo porcentaje atribuido a "motivos de seguimiento" evidencia la necesidad de profundizar estrategias para promoverlo. El PCD oficializó una modalidad de comunicación que canaliza prácticas anteriormente realizadas a través de vías informales, resignificando la gestión como acto asistencial. Contribuyó a la implementación de metodologías de evaluación conjunta de los indicadores considerados, que contemplan el contexto de la población con la que se trabaja (AU)

In 1997, the Outreach Communication Office (OCO) was created at the Pediatric Hospital Juan P. Garrahan with the aim of responding to consultations from remote places and facilitating follow-up of patients while avoiding unnecessary patient transportations. More than 25,000 consultations have been responded. Currently, within the framework of the Program of Outreach Communication (POC), 88 OCO's are operating distributed over 12 of the 23 Argentine provinces. Here we present the results of a sample of 148 consultations made at the Garrahan Hospital from six provinces that participated in a descriptive, retrospective, qualitative and quantitative study. The study allowed formulation of new methods of task registration and the development of qualitative and quantitative indicators to evaluate the POC: consultations, reason for consultation, type of patient, urgency of the consultation, disease duration until the moment of consultation, suggested referral, and time to response. The number of consultations and suggestions for referral were analyzed showing a progressive and significant increase of the former since the implementation of the POC. Of the reasons for consultation, 84% was related to definition of diagnosis and treatment, 16% to follow-up and intercurrencies. Of all patients, 62% had chronic diseases and 95% were considered complex patients. Of the consultations, 79% were defined as essential and 54% of the patients were referred to specialists. Mean time to response was 48 hours. The low percentage of consultations for "reasons of follow-up" reveals the need to develop strategies to encourage this modality. The POC has officialized a means of communication channeling practices that previously were informal giving a new meaning to the concept management in health care. The POC has contributed to the implementation of methodologies for the assessment of global markers taking into account the context of the population in question (AU)

Farm animal feeders: another group affected by cereal flour asthma.

Asthma induced by cereal flour is a long recognized entity. We present studies of three patients affected by asthma related to exposure to cereal flour contained in animal formula feeds. Skin prick test performed with the formula feed components showed positive reactions to cereal flours (wheat, rye and barley) and negative to the other substances in these formulas. Specific anti-wheat, rye and barley flour IgE antibodies were found by RAST. Bronchial provocation tests (BPT) with wheat flour (patients 1 and 2) and barley flour (patient 3) all showed immediate responses. These findings suggest that our patients' symptoms were caused by an IgE-mediated hypersensitivity to cereal flours from animal formula feeds. We call attention to the importance of cereal flours in animal formula feeds as a cause of occupational asthma in farm and animal feeders.

Specific bronchial challenge in cockroach asthma.

Clinical characteristics of allergic asthma due to inhalation of cockroach antigens have been reported sporadically in the literature. To assess the patterns of bronchial response in cockroach asthma we performed bronchial provocation tests (BPT) with cockroach extract in 25 asthmatic patients who had positive skin test with this extract. Of 25 patients, 23 had cockroach-specific-IgE-antibodies. Seventeen subjects presented only immediate asthmatic reaction, five patients had dual response (immediate + late), and one patient developed only late asthmatic response. BPT were negative in two patients who did not have cockroach-specific-IgE-antibodies. These results indicate that BPT with cockroach antigen is a very specific test for cockroach asthma. It shows immediate, dual and late responses, and correlates well with the presence of specific IgE antibodies against this allergen.

Occupational asthma caused by Voacanga africana seed dust.

We report a case of a nonatopic patient in whom exposure to Voacanga africana (VA) dust precipitated asthma. The patient was indirectly exposed to this dust by her husband, a chemist working in a pharmaceutical plant in which VA is used for the production of vinburnine, an alkaloid derivative. Vinburnine (Cervoxan) is widely used in conditions associated with cerebral circulatory insufficiency. Studies revealed the presence of immediate skin test reactivity to VA dust, and specific anti-VA antibodies were detected in the patient's serum by the reverse enzyme immunoassay technique. Bronchial challenge with a VA extract also resulted in an immediate asthmatic response without late reaction. These findings suggest a type I IgE-mediated immunologic mechanism as being responsible for the patient's respiratory symptoms. Unexposed persons did not exhibit reactivity to this seed with any of the tests referred to above. To the best of our knowledge, this is the first reported case of occupational asthma caused by VA seeds.

Anaphylaxis after intra-articular injection of orgotein. Detection of an IgE-mediated mechanism.

Orgotein, a recently introduced anti-inflammatory agent, is the generic name accepted in the U.S.A. for the drug version of copper-zinc superoxide dismutase. This metallo-enzyme is obtained from bovine liver and has a molecular weight of about 32,000. We report on a patient to whom an intra-articular injection of orgotein caused an anaphylactic reaction. An IgE-mediated mechanism was suggested by an immediate positive skin test to orgotein and by the finding of specific IgE against orgotein in the patient's serum.

Hereditary angioedema: a study of three families.

Familial angioedema is an autosomal dominant hereditary disease whose pathogenesis is attributed to a C1 inhibitor (C1 INH) deficit. Two genetic forms have been recognized related to the C1 inhibitor deficiency or its dysfunction. Antifibrinolytics as well as androgenic derivatives have proved to be effective in the prevention and treatment of this pathology. In this paper we present the studies carried out in three families affected by C1 inh. deficit and the treatment employed. Some of the members of these families showed symptoms related with this deficit. A satisfactory explanation has not been formulated to justify the reason why only some of the members in our study showed symptomatology, given that there were no differences between the C1 inh. levels in these patients and those who were not affected. The absence of family history connected with this disease does not necessarily suggest that a genetic mutation has been produced. This deficit could have been present in earlier generations but without clinical manifestations. Stanozolol proved effective in the control of symptoms in the two patients to whom this treatment was applied. However, the rise of C1 inh. levels was significative only in one of them. The lack of connection between the clinical improvement and the normalization of the C1 inh. levels led us to think that the main goal of the therapy should not be directed to the normalization of these levels but to keep the patient asymptomatic with the lowest possible doses of the selected medication.

Severe anaphylactoid reaction to nalidixic acid.

We present the case of a 58-year-old non-atopic woman who suffered an adverse reaction to orally administered nalidixic acid, which had been prescribed for the treatment of a urinary tract infection. The single-blind oral provocation test was positive; the patient presented the clinical features of an anaphylactoid reaction 3 min after administration of nalidixic acid. Both the skin test and the histamine release test were negative. These results suggest that we are dealing with an anaphylactoid reaction not described before with this drug.

Cockroach hypersensitivity in asthmatic patients.

Hypersensitivity to cockroach antigen has been recognized as an important cause of perennial allergic rhinitis and asthma. To assess the frequency of cockroach hypersensitivity in our country, 150 asthmatic atopic subjects were studied using skin testing and in vitro assays for cockroach-specific IgE antibodies (Oriental and German cockroaches). Twenty-two of 61 patients who had a positive history of cockroach exposure had positive skin tests, and only 3 of 89 patients who had no history of exposure had positive skin reactions. Of 25 patients with positive skin tests, 23 showed specific IgE antibodies against oriental and German cockroaches using RAST and EIA techniques. In summary, approximately 15% of asthmatic atopics in Madrid area are sensitive to cockroaches (positive skin test + specific IgE antibodies). These results indicate that cockroach hypersensitivity should be considered in every patient with perennial asthma.

Cockroach asthma: case report and literature review.

Among the different antigens, insects play an important role in the induction of allergic reactions. We report on a 12-year-old boy with family history of atopy, who developed symptoms of rhinitis and perennial asthma since the age of 5. Patient's symptomatology increased during pollination and kept close relationship to domestic antigens. A skin and inhalation test with an extract of domestic dust was positive. An investigation about potential allergens was initiated and the patient mentioned that was a significant amount of cockroaches at his home. Skin tests, RAST and bronchial provocative tests with a cockroach extract gave positive results. Bronchial provocative tests with a cockroach extract gave immediate and late responses, as has been evidenced by different authors. Immunotherapy has been successfully employed, partly due to the difficulties inherent to an efficient way of preventing insect contact. Improvement of symptomatology correlates well with blocking antibody production and the reduction in white cell sensitivity to the antigenic system. Finally, the potential relevance of cockroach hypersensitivity in our country be underlined. Cockroach sensitivity should be considered in every patient with perennial asthma, in which the usual allergens have been excluded.

Asthma caused by African maple (Triplochiton scleroxylon) wood dust.

Inhalation of wood dusts can cause immediate and/or late onset asthma, and the list of woods responsible for such reactions is increasing. We report two patients with asthma induced by exposure to the dust of African maple wood (Triplochiton scleroxylon). Type I hypersensitivity to this dust was demonstrated by means of immediate skin test reactivity, positive passive transfer test, positive reverse enzyme immunoassay for specific IgE, and an immediate bronchial provocation test response to an African maple-dust extract. Unexposed persons did not exhibit reactivity to this wood in any of the tests listed above.

Allergy to amoxicillin in patients who tolerated benzylpenicillin, aztreonam, and ceftazidime.

The usual battery of skin tests employed for determining penicillin allergy may fail to detect allergic reactions to side chain-specific beta-lactam agents. We report the cases of six patients who experienced anaphylactic reactions after treatment and challenge with amoxicillin but who tolerated parenteral challenges with benzylpenicillin, aztreonam, and ceftazidime. Results of skin tests for amoxicillin (10 mg/mL) were positive for four of the six patients.