Beliefs and attitudes about deprescription in older HIV-infected patients: ICARD Project.

OBJECTIVE: HIV population is aging at an earlier age than those uninfected, requiring more non-HIV medications to treat noncommunicable diseases. In the context of chronic HIV infection, the next therapeutic change would be the polymedication control. This paper has the purpose of explore the attitudes of older people living with HIV toward deprescribing. METHODS: This was an observational, prospective and multicenter study conducted from March-April, 2018. People living with HIV (PLWH) on highly active antiretroviral therapy and older than 65 years were included. In addition to demographic and pharmacotherapeutic data, attitudes regarding deprescribing were collected through the "Revised Patients' Attitudes Towards Deprescribing Questionnaire". RESULTS: A total of 42 patients were included in this study. Regarding their attitudes in relation to deprescription, there were three statements with the most consensuses. The first ("I have a good understanding of the reasons I was prescribed each of my medicines") had 91.9% consensus. The second and third questions showed 89.2% consensus in both cases; "Overall, I am satisfied with my current medicines" and "I like to be involved in making decisions about my medicines with my doctors". CONCLUSIONS: This study is the first to explore the beliefs and attitudes of older PLWH in relation to deprescription process. There are positive attitudes regarding medication knowledge but there also is a percentage of patients who had a negative opinion regarding deprescription. We must study and go deeper in our knowledge of techniques that could help us to better understand their preferences, in order to establish effective and successful deprescription strategies.

Optimizing reproducibility evaluation for random amplified polymorphic DNA markers.

The random amplified polymorphic DNA (RAPD) technique is often criticized because it usually shows low levels of repeatability; thus it can generate spurious bands. These problems can be partially overcome by rigid laboratory protocols and by performing repeatability tests. However, because it is expensive and time-consuming to obtain genetic data twice for all individuals, a few randomly chosen individuals are usually selected for a priori repeatability analysis, introducing a potential bias in genetic parameter estimates. We developed a procedure to optimize repeatability analysis based on RAPD data, which was applied to evaluate genetic variability in three local populations of Tibochina papyrus, an endemic Cerrado plant found in elevated rocky fields in Brazil. We used a simulated annealing procedure to select the smallest number of individuals that contain all bands and repeated the analyses only for those bands that were reproduced in these individuals. We compared genetic parameter estimates using HICKORY and POPGENE softwares on an unreduced data set and on data sets in which we eliminated bands based on repeatability of individuals selected by simulated annealing and based on three randomly selected individuals. Genetic parameter estimates were very similar when we used the optimization procedure to reduce the number of bands analyzed, but as expected, selecting only three individuals to evaluate the repeatability of bands produced very different estimates. We conclude that the problems of repeatability attributed to RAPD markers could be due to bias in the selection of loci and primers and not necessarily to the RAPD technique per se.

[Assessment of the severity scores in patients included in a sepsis code in an Emergency Departament]. / Valoración de escalas de gravedad en pacientes incluidos en un código sepsis en un servicio de urgencias hospitalario.

OBJECTIVE: The objective of the study is to determine the usefulness of the SOFA (Sequential Organ Failure Assessment), quick SOFA (qSOFA), LODS (Logistic Organ Dysfunction System) and EWS (Early Warning Score) scores to predict in-hospital mortality among septic patients attended in the emergency department; to evaluate what factors are associated with mortality; and develop a predictive model of in-hospital mortality. METHODS: Retrospective study including patients over 14 years of age included in the sepsis code of an Emergency Department of a University Hospital between November 2013 and September 2015. Demographic variables, hemodynamic and analytical variables, and in-hospital mortality were collected to obtain qSOFA, SOFA, LODS, EWS scores. Receiver operating characteristic curves were constructed for each score. Logistic regression was used to evaluate the probability of in-hospital mortality. RESULTS: A total of 349 patients were analyzed, median age 72.7 (range 86), males: 54.4%. The in-hospital mortality was 21.8%. AUC obtained: LODS: 0.73 (IC 95% 0.67-0.80; p<0.001), EWS: 0.73 (IC 95% 0.65-0.81; p<0.001), SOFA: 0.72 (IC 95% 0.65- 0.78; p<0.001), qSOFA: 0.67 (IC 95% 0.58-0.76; p<0.001). After the multivariate analysis, these were the independent factors associated with in-hospital mortality: Oxygen saturation ≤92%, Glasgow coma score <14, lactate ≥2mmol/L (p<0.05). Two prognostic models were generated: MPRO1: age, oxygen saturation ≤92% and Glasgow coma score <14, AUC: 0.78 (IC 95% 0.72-0.84; p<0.001) and MPRO2 formed by the previous ones and lactate ≥2mmol/L, AUC: 0.82 (IC 95% 0.76-0.87; p<0.001). CONCLUSIONS: SOFA score and the new developed scores could be useful in asses the risk of in-hospital mortality in patients included in the sepsis code.

Impact of a stewardship program on bacteraemia in adult inpatients.

OBJECTIVE: Bloodstream infections (BSIs) are associated with considerable morbidity and mortality among inpatients. The aim of this study was to evaluate the impact of a stewardship program on clinical and antimicrobial therapy-related outcomes in patients with bacteraemia. METHODS: Single-centre, before-and-after quasi-experimental study in adult inpatients. Over 1 January 2013 to 31 June 2013 all patients aged 18 years or older with a bacteraemia (interven-tion group, N=200) were compared to a historical cohort (1 Janu-ary 2012 to 31 December 2012) (control group, N=200). RESULTS: Following blood culture results and adjusting for potential confounders, the stewardship program was associated with more changes to antibiotic regimens (adjusted odds ratio [ORa]: 4.6, 95% CI 2.9, 7.4), more adjustments to antimicrobial therapy (ORa: 2.4, 95% CI 1.5, 3.8), and better source control in the first five days (ORa 1.6, 95% CI: 1.0, 2.7). In the subgroup that initially received inappropriate empiric treatment (n=138), the intervention was associated with more antibiotic changes (OR: 3.9, 95% CI: 1.8, 8.5) and a better choice of definitive antimicrobial therapy (OR 2.3 95% CI: 1.2, 4.6). There were also more antibiotic changes in the subgroups with both Gram-negative (OR: 2.8, 95% CI: 1.6, 4.9; n=217) and Gram-positive (OR: 4.6, 95% CI: 1.8, 9.9; n=135) bacteraemia among those receiving the intervention, while the Gram-positive subgroup also received more appropriate definitive antimicrobial therapy (OR: 3.9, 95% CI: 1.8, 8.8). CONCLUSIONS: The stewardship program improved treatment of patients with bacteraemia and appropriateness of therapy.

Visual hallucinations associated with Parkinson disease.

OBJECTIVE: To determine factors that are predictive for the development of hallucinations associated with Parkinson disease (PD). BACKGROUND: Hallucinations are a common difficulty for patients with established PD, and hallucinations and psychosis may be the most common causes for nursing home placement. The characteristics of the hallucinations associated with PD differ from the hallucinations associated with schizophrenia or cocaine abuse. Multiple factors have been suggested as causal. DESIGN AND METHODS: A total of 214 consecutive patients were interviewed during routine visits to the Parkinson's Disease Clinics in Columbus, Ohio, and Miami, Fla, using a hallucination questionnaire, Folstein Mini-Mental State Examination, and an attempt to correlate age, duration of disease, medication, and psychological or sleep disorders with the hallucinations. RESULTS: Hallucinations were almost exclusively visual and were present in 55 of the 214 patients. Dementia, age, duration of disease, history of depression, or history of sleep disorder were strongly associated with the hallucinations. CONCLUSIONS: While reduction in levodopa and anticholinergic medication doses is appropriate in the management of hallucinations, the factors that predispose patients to hallucinations include dementia and advancing age. The phenomena of visual hallucinations associated with PD, while not fully explained, are unique enough to be of interest to all neurologists and neuroscientists.

Levodopa, melanoma, and Parkinson's disease.

Previous reports and the Physicians' Desk Reference caution against the use of levodopa in Parkinson's disease (PD) patients with melanoma. A critical review of the literature reveals only anecdotal evidence to support a link between levodopa and melanoma. In fact, levodopa has an antitumor effect on melanoma. We report nine patients with PD and melanoma who were treated with levodopa/carbidopa (L/C). Current evidence suggests that L/C can be used safely in PD patients with a history of melanoma.

Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson's disease.

Early combination therapy with bromocriptine (Br) and levodopa (LD) is believed to delay or prevent the onset of late treatment complications typically associated with LD monotherapy in Parkinson's disease (PD). Studies recommending this regimen have been uncontrolled. We evaluated this possibility in a 4-year, double-blind, randomized, parallel group trial comparing Br and LD both alone and in combination in 22 PD patients never before treated with dopaminergic medications. In the group receiving Br monotherapy, 17% had motor fluctuations (end-of-dose failure or on-off), 17% chorea, 33% dystonia, and 83% freezing. In the LD group, 33% had motor fluctuations, 56% chorea, 100% dystonia, and 22% freezing. In the combination group, 71% had motor fluctuations, 57% chorea, 71% dystonia, and 57% freezing. The frequency of dystonia was significantly lower with Br monotherapy than in the other two treatment groups. No other significant differences were observed. LD monotherapy appeared to have superior efficacy in the treatment of PD. Mean final doses of LD and Br were similar for the different treatment groups. Early combination therapy does not prevent or delay the onset of motor fluctuations or dyskinesia in PD.

Ultrasonic detection of red cell aggregation immediately preceding blood clotting.

High-resolution ultrasonic imaging of circulating blood was used to study the relation between red cell aggregation and blood clotting in vitro. A reversible increase in echogenicity produced by red cell aggregation occurred in moving heparinized blood as shear rate was decreased. We induced clotting of the heparinized blood by administration of protamine. At both low (1.6 sec-1) and moderate (22.6 sec-1) mean shear rates, transient homogenous increased echogenicity indicative of red cell aggregation preceded blood clotting. In separate experiments, we established that protamine can cause increased echogenicity due to red cell aggregation which can be reversed by adding heparin to circulating suspended red cells in the absence of clotting factors. Presumably, these effects of protamine and heparin are due to electrostatic bonding involving red cell surfaces. We conclude from these studies that red cell aggregation precedes clotting of heparinized blood by protamine at low and moderate shear rates.

MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices.

Since MPTP and its metabolite MPP+ produce nigrostriatal lesions and symptoms similar to Parkinson's disease, recent studies have aimed toward defining their selectivity and neurotoxic mechanisms. In mitochondria in vitro, MPP+ blocked electron transport and decreased oxygen consumption. However, these effects were not selective to striatal mitochondria or even to mitochondria from brain, they required concentrations of MPP+ much greater than those found in vivo, and physiological actions could not be related to intramitochondrial changes. Lower doses of MPP+ did produce highly selective degeneration of dopaminergic (DA) neurons in cell cultures. We report here that MPP+ provoked large (80%) oxidations of cytochrome b and large K+o increments (approximately 30 mM) in rat striatal slices. These effects were slowed by mazindol, which inhibits DA uptake, and were markedly attenuated in rat hippocampal slices which have little DA input. Since DA terminals comprise only 2-4% of the striatal mass, the large MPP+-induced changes suggest that while MPP+ neurotoxicity in brain requires the presence of functioning DA terminals, effects are not confined to these terminals. Such studies illustrate the complexity of MPP+ neurotoxicity and demonstrate the importance of investigations in models such as brain slices with an extracellular space and intracellular relationships as in intact brain.

MPP+-induced increases in extracellular potassium ion activity in rat striatal slices suggest that consequences of MPP+ neurotoxicity are spread beyond dopaminergic terminals.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces symptoms similar to idiopathic Parkinson's disease in primates. A metabolite of MPTP, MPP+ (1-methyl-4-phenylpyridinium), is actively accumulated by dopaminergic (DA) terminals and selectively destroys nigrostriatal DA neurons. The mechanism of this effect remains unknown but reports that MPP+ inhibits electron transport in isolated mitochondria and increases oxidation of cytochrome b in striatal slices suggest that depression of ATP production is involved. To relate metabolic effects of MPP+ with tissue electrophysiology, extracellular potassium ion activity [K+]o was measured by microelectrodes simultaneous to optical monitoring of reduction/oxidation (redox) activity of cytochrome b during superfusion of MPP+ onto rat striatal and hippocampal slices. MPP+ increased oxidation of cytochrome b and increased [K+]o in slices of striatum. These increases were greater than expected from a selective effect of MPP+ on DA terminals which likely comprise no more than 3% of the total striatal mass. These effects of MPP+ were slowed by a dopamine uptake inhibitor (mazindol) and did not occur in hippocampal slices. These findings indicate that MPP+ influences ion transport as well as metabolic activity and that these actions require the presence of functioning DA terminals. However, the large amplitudes of the MPP+-induced changes suggest that consequences of MPP+-neurotoxicity are not ultimately confined to DA terminals. Two hypothesis are proposed: that energy failure in DA terminals results in leakage of neurotoxic substances or metabolites altering membrane conductance properties of adjacent cells and thereby placing additional demand upon ion transport pumps and mitochondrial oxidative phosphorylation; or that there is secondary uptake of MPP+ leading to mitochondrial inhibition in cells neighboring DA terminals.

1-Methyl-4-phenylpyridinium (MPP+) increases oxidation of cytochrome-b in rat striatal slices.

Effects of 1-methyl-4-phenylpyridinium, (the active metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), on reduction/oxidation activity of mitochondrial cytochromes were studied in rat striatal slices using scanning spectrophotometry. The objective was to test the hypothesis that the neurotoxin alters electron transport in the mitochondrial respiratory chain. Incubation of rat striatal slices with MPP+ (1 microM) produced a time-dependent oxidation of Cytochrome-b in a manner consistent with the concept of a block in electron transport in the intramitochondrial respiratory chain between nicotinamide adenine dinucleotide (NAD) and Cytochrome-b. This effect of MPP+ was decreased by co-incubation with a potent dopamine uptake inhibitor (mazindol), or when studied in a tissue with low dopaminergic innervation (hippocampus). The amplitude of Cytochrome-b oxidation was greater than that expected from a selective effect of MPP+ on dopaminergic neurons suggesting that neighboring cells are influenced secondary to the MPP+ effect on dopaminergic terminals.

Role of red cells in preventing the growth of platelet aggregation.

Using high-resolution real-time two-dimensional ultrasound, we have investigated the role of red cells in the growth of already established platelet aggregates under controlled flow conditions. Platelet rich plasma (PRP) was circulated in vitro in horizontally and vertically arranged tubing at mean shear rate ranging from 60 to 0 sec-1, and adenosine diphosphate (ADP) was used to induce platelet aggregation. ADP-induced platelet aggregates grew in size and tended to sediment as shear rate decreased, in particular, below 10 sec-1. At 0 sec-1 (stasis), large clusters of platelet aggregates formed. The addition of washed red cells to produce a hematocrit of only 2% significantly interfered with the growth and sedimentation of platelet aggregates as shear rate was reduced. Formaldehyde-hardened erythrocytes had a similar effect in preventing the growth of platelet aggregates, suggesting that mechanical collision of red cells with platelet aggregates may be the cause of growth inhibition. Therefore, the thrombotic process may be enhanced in red cell poor zones in circulation resulting from flow disturbances associated with vascular stenosis or within artificial organs and extracorporeal systems. The present study also suggested that red cell free PRP should be carefully administered therapeutically.

The use of pramipexole, a novel dopamine (DA) agonist, in advanced Parkinson's disease.

We evaluated the efficacy, safety and tolerability of a new dopamine D-2 receptor agonist, pramipexole [(S)-2-amino-4,5,6,7-tetrahydro-6-propylamino-benzathiazol-dihydro chloride], as adjunctive therapy in patients with advanced Parkinson's disease (PD). Twenty-four PD patients with motor fluctuations were treated in an 11 week prospective, single-blind parallel-group, placebo-controlled trial. The pramipexole treated group experienced a significant improvement in "off" time functioning as measured by the activities of daily living portion of the United Parkinson's Disease Rating Scale. In addition, the active treatment group was able to reduce total levodopa dose by 30% (p < 0.05). Pramipexole was well tolerated and the side effects reported were typical of other dopamine agonists. We conclude that pramipexole has antiparkinsonian effects which make it potentially useful in the treatment of motor fluctuations in PD.

Banisterine and Parkinson's disease.

It is of historical interest that 63 years ago Louis Lewin reported the use of a hallucinogenic compound prepared from the South American vine, Banisteria Caapi, to treat Parkinson's disease (PD). This psychoactive compound, named banisterine, proved to be identical to harmine, but 30 years were to pass before it was shown to be a reversible monoamine oxidase (MAO) inhibitor. The first reports of the use of banisterine to treat postencephalitic parkinsonism in 1929 created a stir in the popular press and banisterine was hailed as a "magic drug." Despite continued studies of the harmala alkaloids by other researchers, interest in the therapeutic value of these compounds vanished during the 1930's. The story of banisterine is reviewed because it was the first MAO inhibitor to be used in parkinsonism, and illustrates the historical role of psychoactive drugs in the development of effective therapies, and in elucidating the pathophysiology of PD.

Traditional and complementary therapies in Parkinson's disease.

Parkinson's disease has existed in different parts of the world since ancient times. The first clear description is found in the ancient Indian medical system of Ayurveda under the name Kampavata. Traditional therapies in the form of herbal preparations containing anticholinergics, levodopa, and monoamine oxidase inhibitors were used in the treatment of PD in India, China, and the Amazon basin. Scientific reevaluation of these therapies may be valuable, as shown in the case of Mucuna pruriens and Banisteria caapi. Complementary therapies such as massage therapy, biofeedback, and acupuncture may have beneficial effects for patients and deserve further study.

Psychostimulants.

Psychomotor stimulants possess intrinsic reinforcing properties that may lead to dependence and abuse. Epidemics of stimulant abuse have occurred historically in cycles related to introduction of new stimulants or new routes of administration. The actions and toxic effects of stimulants are related primarily to interaction with the central and peripheral SNS. The most common complications of stimulant use that result in visits to emergency rooms and hospital admissions are referrable to psychiatric, cardiopulmonary, and neurologic symptoms. Neurologic complications most commonly include seizure and stroke, but relative to the prevalence of stimulant abuse in most cities, the incidence of stroke and seizures is small. Cocaine-associated stroke can be linked to underlying abnormalities of the cerebrovascular system in almost one half of the cases. Other complications such as sudden death, movement disorders, and infection are rare. With repeated use of stimulants, a state of drug dependence develops for which there is at present inadequate treatment. As a consequence, pharmacotherapeutic strategies for treatment of dependence are being explored.

Second-order schedules of intravenous drug self-administration in rhesus monkeys.

Lever-pressing behavior was generated and maintained in 3 rhesus monkeys by intravenous infusions of morphine or cocaine under a second-order schedule of reinforcement. Under this schedule, every tenth lever-press response (FR 10) during a fixed interval of time produced a 2 sec stimulus light. The first FR 10 completed after a 60 min interval had elapsed produced the stimulus light and an intravenous infusion of morphine or cocaine. The stimulus light remained on for the duration of the drug infusion (50-60 sec). Sessions of morphine or cocaine presentation, each with distinct stimulus light conditions, alternated on a daily basis. Under this schedule, single doses of morphine from 0.125 to 1.0 mg/kg maintained high overall response rates (maximum of 40 Rs/min) in the pattern characteristic of fixed interval (FI) schedules of reinforcement. There was no functional relationship between the response-rates and the doses of morphine tested. The simultaneous infusion of naloxone (0.125 mg/kg/) with morphine (0.25 mg/kg) markedly decreased response rates. However, the infusion of the same dose of naloxone five min after the presentation of morphine failed to suppress self-administration behavior. Naloxone had no effects on cocaine-reinforced responding.

Laparoscopic colorectal procedures: a multicenter Brazilian experience.

An evaluation of the results of the Brazilian experience in colorectal laparoscopic procedures in a multicenter prospective protocol done by the Brazilian Society of Colo-Proctology is presented. From December 1991 to August 1998, 1,161 patients (583 men and 578 women; mean age, 49.8 years), were operated on laparoscopically. Most of the procedures (40.5%) were for cancer, and the most common procedure was anterior resection (22.5%). The mean operative time was 189 minutes (3.1 hours). There were 42 (3.6%) perioperative complications; visceral injuries were the most common (1.4%). Conversions occurred in 122 (10.5%) cases. There were 148 (12.7%) postoperative complications; wound infections were the most common (5.2%). A liquid diet was started at a mean time of 1.4 days after the operation, and the mean hospitalization period was 6.4 days.

[Duodenal gangliocytic paraganglioma]. / Paraganglioma gangliocítico duodenal.

We report a case of duodenal Gangliocytic Paranglioma in a 73 year old man, who presented with a history of melena. An upper gastrointestinal barium study showed a polyp located in the second portion of the duodenum. This lesion was endoscopically resected. Pathological examination revealed a Gangliocytic Paraganglioma. We describe the general characteristics of this neoplasm, as well as the theories about its histogenesis.

[Pulmonary mechanics in the full-term newborn]. / Mecânica pulmonar no recém-nascido normal.

The objective of this study is evaluate the pulmonary function in full term newborn infants, comparing classic with non-invasive techniques. We describe the pulmonary function laboratory and software developed at Instituto Fernandes Figueira. We studied 10 healthy full-term newborn infants (birthweight 3.260 g + - 460 g) Occlusions were performed at inspiration end and during expiration which allowed us to calculate values for total pulmonary resistance (TPR) and total pulmonary compliance (TPC). Esophageal pressure was measured with a water filled catheter positioned in the lower third of the esophagus, to obtain lung resistance (RL) and compliance (CL). All signals were digitized at 60 Hz into a microcomputer for further analysis. Mean results of our study are: CL= 1.78 + - 0.36 ml/cm H(2)O/kg, TPC= 1.12 + - 0.27 ml/cm H(2)O/kg and TPR= 16 + - 4 cm H(2)O/l/seg/kg. Our values are very similar to the ones in the current literature.