965 resultados para risperidone long-acting injection (LAI)


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We measured plasma tafenoquine concentrations in Thai soldiers given a monthly regimen of tafenoquine to determine whether these concentrations adequately suppressed malarial infections on the Thai- Cambodian border. After receiving a treatment course of artesunate and doxycycline, 104 male soldiers were administered a loading dose of tafenoquine ( 400 mg daily for 3 days), followed by tafenoquine monthly ( 400 mg every 4 weeks) for 5 months. Consecutive monthly mean ( +/- standard deviation) trough plasma tafenoquine concentrations were 223 +/- 41, 127 +/- 29, 157 +/- 51. 120 +/- 24, and 88 +/- ng/ mL. Only 1 soldier developed malaria during the study. At the time of malaria diagnosis, his plasma tafenoquine concentration was 40 ng/ mL, which was similar to 3- fold lower than the trough concentrations of the other soldiers. Although low tafenoquine concentrations appear to be uncommon, additional investigations are needed to determine the relationship between plasma tafenoquine concentrations and suppression of malaria.

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INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

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Acknowledgments The authors thank Prof. Stanley Szefler for his comments on the paper and Lisa Law for help with editing

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Data access and analyses were funded by Boehringer Ingelheim, who played no role in the conduct or reporting of the study.

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Background: Haiti has the highest maternal mortality rate in the Latin American and Caribbean region. Despite the fact that Haiti has received twice as much family planning assistance as any other country in the western hemisphere, the unmet need for contraception remains particularly high. Our hypothesis is that unsuccessful efforts of family planning programs may be related to a misconstrued understanding of the complex role of gender in relationships and community in Haiti. This manuscript is one of four parts of a study that intends to examine some of these issues with a particular focus on the influence of uptake and adherence to long acting contraceptive (LAC) methods.

Methods: We conducted a three-month community-based qualitative assessment through 20 in-depth interviews in Fondwa, Haiti. Participants were divided into 4 groups of five: female users, female non-users, men and key community stakeholders.

Results: Based on the qualitative interviews, we found that main barriers included lack of access to family planning education and services and concerns regarding side effects and health risks, especially related to menstrual disruption and fears of infertility. Women have a constant pressure to remain fertile and bear children, due not only to social but also economic needs. As relationships are conceived as means for economic provision, the likelihood of uptake of irreversible methods (vasectomy and tubal ligation) was restricted by loss of fertility. Consequently, the discourse of family planning, though self-recognized in their favor, assumes women can afford not to bear children. This assumption should be questioned given the complexities of the other social determinants at play, all which affect the reproductive decisions made by Haitians.

Conclusions: Overall, our study indicated awareness surrounding contraception in the Haitian Fondwa community. Combining the substantial impact of birth spacing with the elevated yet unmet need for contraceptives in the area, it is necessary to address the intricacies of gender issues in order to implement successful programing. In Haiti not being able to bear a child poses a threat to economic and social survival, possibly explaining a dimension of the low uptake of LACs in the region, even when made available. For this reason, we believe IUDs (Intrauterine Devices) provide a suitable alternative, allowing the couple to comprehend all of the factors involved in decision making, thus decreasing the imbalances of power and knowledge prior to considering an irreversible alternative.

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Background Both contraceptive use and fertility rates are high fertility in Malawi. Status of women remains low and is believed to affect reproductive health decisions including use of Long Acting and Permanent Contraceptives Method (LAPCM). Objective This study seeks to examine the relationship between women empowerment and LAPCM. A measure of women’s empowerment is derived from the women’s responses to questions on the number of household decisions in which the respondent participates, employment status, type of earnings, women’s control over cash earnings and level of education. Methods The study is based on a sub sample of 5,948 married women from the 2010 Malawi Demographic and Health Survey. Data was analysed using descriptive statistics, Chi-square and multinomial logistic regression models (α=5%). Results The prevalence of current use of LAPCM was 20.0% and increases with increasing empowerment level (p<0.001). Mean age and empowerment score of women who are currently using LAPCM were 38.53±6.2 years and 6.80±2.9 respectively. Urban women (22.2%) were more currently using LAPCM than rural women (19.4%) p<0.001. Women who belong to Seven Day Adventists/Baptist were 1.51(C.I=1.058-2.153; p=0.023) more likely and Muslims were 0.58(C.I=0.410-0.809; p=0.001) less likely to currently use LAPCM than Catholic women. Being in the richest wealth quintile (OR=1.91; C.I=1.362-2.665; p<0.001) promotes current use of LAPCM than poorest. The likelihood of currently using LAPCM was higher among women who have access to FP programmes on media and increases consistently with increasing women empowerment level even when other potential confounding variables were used as control. Conclusion In Malawi, LAPCM is still underutilized and more than half of the women are not adequately empowered. Women empowerment, wealth quintile and access to FP programmes are key factors influencing the use of LAPCM. Programmes that address these determinants are urgently needed in Malawi.

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Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzmann rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 mug/mul) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 mug/mul) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 mug/mul) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/mul) injected into LV increased into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 mug/mul, isoproterenol produced and additive effect on pilocarpine-induced salivary secretion. The 40-nmol/mul dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/mul), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced and increase in salivary secretion. The 40-nmol/mul dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated. (C) 2002 Elsevier B.V. All rights reserved.

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Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

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Aging is associated with an increased incidence of glucose intolerance and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an important insulinotropic peptide secreted from the gastrointestinal tract in response to nutrient absorption. The present study was designed to assess the sub-chronic glucose regulatory effects of the potent long-acting GLP-1 receptor agonist, (Val(8))GLP-1, in aging 45-49 week old mice. Daily injection of (Val$)GLP-1 (25 nmol/kg body weight) for 12 days had no significant effect on food intake, body weight, non-fasting plasma glucose and insulin concentrations. However, after 12 days, the glycaemic response to intraperitoneal glucose was improved (P <0.05) in (Val(8))GLP-1 treated mice. In keeping with this, glucose-mediated insulin secretion was enhanced (P <0.05) and insulin sensitivity improved (P <0.05) compared to controls. These data indicate that sub-chronic activation of the GLP-1 receptor by daily treatment with (Val(8))GLP-1 counters aspects of the age-related impairment of pancreatic beta-cell function and insulin sensitivity. 2006 Elsevier Inc. All rights reserved.

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Introduction & Objectifs : Pour assurer l’analgésie postopératoire, l’anesthésiste dispose, en plus des différentes classes de médicaments administrés par voie orale ou intraveineuse, de diverses techniques pour bloquer l’influx nerveux douloureux en administrant les anesthésiques locaux (AL) de manière centrale ou périphérique. La ropivacaïne (ROP), un AL à longue durée d’action, est un médicament de première intention partout dans le monde, en raison de sa grande efficacité et de son faible risque de toxicité. Contrairement à certains pays, la ROP n'est toujours pas indiquée au Canada pour la rachianesthésie (bloc central) en raison d'un manque de données probantes. Jusqu'à présent, les efforts de recherche ont essentiellement porté sur la sécurité ainsi que sur la durée d’action du médicament lorsqu’administré par voie spinale. De plus, les doses optimales de ROP pour l’anesthésie régionale périphérique ne sont pas encore précisément connues. La posologie devrait être adaptée au site d’administration ainsi qu’à l’intensité et la durée du stimulus produit par la chirurgie. Ultimement, cela permettrait aux cliniciens d’identifier le régime optimal en fonction des facteurs démographiques qui pourraient affecter la pharmacocinétique (PK) et la pharmacodynamie (PD) de l’AL (objectif global de ces travaux). Validation de la Méthode Analytique Manuscrit 1 : Une méthode analytique spécifique et sensible permettant de déterminer les concentrations plasmatiques de ROP a d’abord été optimisée et validée. Validation du Biomarqueur Manuscrit 2 : Nous avons ensuite mis au point et évalué la fiabilité d’une méthode quantitative basée sur la mesure du seuil de perception sensorielle (CPT) chez le volontaire sain. Ce test nécessite l’application d’un courant électrique transcutané qui augmente graduellement et qui, selon la fréquence choisie, est capable de stimuler spécifiquement les fibres nerveuses impliquées dans le cheminement de l’influx nerveux douloureux. Les résultats obtenus chez les volontaires sains indiquent que la mesure CPT est fiable, reproductible et permet de suivre l’évolution temporelle du bloc sensitif. Études cliniques Manuscrit 3 : Nous avons ensuite caractérisé, pendant plus de 72 h, l’absorption systémique de la ROP lorsqu’administrée pour un bloc du nerf fémoral chez 19 patients subissant une chirurgie du genou. Le modèle PK populationnel utilisé pour analyser nos résultats comporte une absorption biphasique durant laquelle une fraction de la dose administrée pénètre rapidement (temps d’absorption moyen : 27 min, IC % 19 – 38 min) dans le flux sanguin systémique pendant que l’autre partie, en provenance du site de dépôt, est redistribuée beaucoup plus lentement (demi-vie (T1/2) : 2.6 h, IC % 1.6 – 4.3 h) vers la circulation systémique. Une relation statistiquement significative entre l’âge de nos patients et la redistribution de l’AL suggère que la perméabilité tissulaire est augmentée avec l’âge. Manuscrit 4 : Une analyse PK-PD du comportement sensitif du bloc fémoral (CPT) a été effectuée. Le modèle développé a estimé à 20.2 ± 10.1 mg la quantité de ROP nécessaire au site d’action pour produire 90 % de l’effet maximal (AE90). À 2 X la AE90, le modèle prédit un début d’action de 23.4 ± 12.5 min et une durée de 22.9 ± 5.3 h. Il s’agit de la première étude ayant caractérisé le comportement sensitif d’un bloc nerveux périphérique. Manuscrit 5 : La troisième et dernière étude clinique a été conduite chez les patients qui devaient subir une chirurgie du genou sous rachianesthésie. Tout comme pour le bloc du nerf fémoral, le modèle PK le plus approprié pour nos données suggère que l’absorption systémique de la ROP à partir du liquide céphalo-rachidien est biphasique; c.à.d. une phase initiale (T1/2 : 49 min, IC %: 24 – 77 min) suivie (délai: 18 ± 2 min) d'une phase légèrement plus lente (T1/2 : 66 min, IC %: 36 – 97 min). L’effet maximal a été observé beaucoup plus rapidement, soit aux environs de 12.6 ± 4.9 min, avant de revenir aux valeurs de base 210 ± 55 min suivant l’administration de l’agent. Ces données ont permis d’estimer une AE50 de 7.3 ± 2.3 mg pour l'administration spinale. Conclusion : En somme, ces modèles peuvent être utilisés pour prédire l’évolution temporelle du bloc sensitif de l’anesthésie rachidienne et périphérique (fémorale), et par conséquent, optimiser l’utilisation clinique de la ROP en fonction des besoins des cliniciens, notamment en ce qui a trait à l’âge du patient.

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Pain relief for removal of femoral sheath after cardiac procedures
Procedures for the non-surgical management of coronary heart disease include balloon angioplasty and intracoronary stenting. At the start of each procedure an introducer sheath is inserted through the skin (percutaneously) into an artery, frequently a femoral artery in the groin. This allows the different catheters used for the procedure to be exchanged easily without causing trauma to the skin. At the end of the procedure the sheath is removed and, if the puncture site isn't "sealed" using a device closure, firm pressure is required over the site for 30 minutes or more to control any bleeding and reduce vascular complications. Removing the sheath and the firm pressure required to control bleeding can cause pain, although this is generally mild. Some centres routinely give pain relief before removal such as intravenous morphine, or an injection of a local anaesthetic in the soft tissue around the sheath (called a subcutaneous injection). Adequate pain control during sheath removal is also associated with a reduced incidence of a vasovagal reaction, a potentially serious complication involving a sudden drop of blood pressure and a slowed heart rate. Four studies were reviewed in total. Three trials involving 498 participants compared subcutaneous lignocaine, a short acting local anaesthetic, with a control group (participants received either no pain relief or an inactive substance known as a placebo). Two trials involving 399 people compared intravenous opioids (fentanyl or morphine) and an anxiolytic (midazolam) with a control group. One trial involving 60 people compared subcutaneous levobupivacaine, a long acting local anaesthetic, with a control group. Intravenous pain regimens and subcutaneous levobupivacaine appear to reduce the pain experienced during femoral sheath removal. However, the size of the reduction was small. A significant reduction in pain was not experienced by participants who received subcutaneous lignocaine or who were in the control group. There was insufficient data to determine a correlation between pain relief administration and either adverse events or complications. Some patients may benefit from routine pain relief using levobupivacaine or intravenous pain regimens. Identifying who may potentially benefit from pain relief requires clinical judgement and consideration of patient preference. The mild level of pain generally experienced during this procedure should not influence the decision as some people can experience moderate levels of pain.

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PURPOSE: The purpose of this study was to assess the impact of different policies on access to hormonal contraception and pregnancy rates at two high school-based clinics. METHODS: Two clinics in high schools (Schools A and B), located in a large urban district in the southwest US, provide primary medical care to enrolled students with parental consent; the majority of whom have no health insurance coverage. The hormonal contraceptive dispensing policy of at School clinic A involves providing barrier, hormonal and emergency contraceptive services on site. School clinic B uses a referral policy that directs students to obtain contraception at an off-campus affiliated family planning clinic. Baseline data (age, race and history of prior pregnancy) on female students seeking hormonal contraception at the two clinics between 9/2008-12/2009 were extracted from an electronic administrative database (AHLERS Integrated System). Data on birth control use and pregnancy tests for each student was then tracked electronically through 3/31/2010. The outcomes measures were accessing hormonal contraception and positive pregnancy tests at any point during or after birth control use were started through 12/2009. The appointment keeping rate for contraceptive services and the overall pregnancy rates were compared between the two schools. In addition the pregnancy rates were compared between the two schools for students with and without a prior history of pregnancy. RESULTS: School clinic A: 79 students sought hormonal contraception; mean age 17.5 years; 68% were > 18 years; 77% were Hispanic; and 20% reported prior pregnancy. The mean duration of the observation period was 13 months (4-19 months). All 79 students received hormonal contraception (65% pill and 35% long acting progestin injection) onsite. During the observation period, the overall pregnancy rate was 6% (5/79); 4.7% (3/63) among students with no prior pregnancy. School clinic B: 40 students sought hormonal contraception; mean age 17.5 years; 52% > 18 years; 88 % were Hispanic; and 7.5% reported prior pregnancy. All 40 students were referred to the affiliated clinic. The mean duration of the observation period was 11.9 months (4-19 months). 50% (20) kept their appointment. Pills were dispensed to 85% (17/20) and 15% (3/20) received long acting progestin injection. The overall pregnancy rate was 20% (8/40); 21.6% (8/37) among students with no prior pregnancy. A significantly higher frequency of students seeking hormonal contraception kept their initial appointment for birth control at the school dispensing onsite contraception compared to the school with a referral policy for contraception (p<0.05). The pregnancy rate was significantly higher for the school with a referral policy for contraception compared to the school with onsite contraceptive services (p< 0.05). The pregnancy rate was also significantly higher for students without a prior history of pregnancy in the school with a referral policy for contraception (21.6%) versus the school with onsite contraceptive services (4.7%) (p< 0.05). CONCLUSION: This preliminary study showed that School clinic B with a referral policy had a lower appointment keeping rate for contraceptive services and a higher pregnancy rate than School clinic A with on-site contraceptive services. An on-site dispensing policy for hormonal contraceptives at high school-based health clinics may be a convenient and effective approach to prevent unintended first and repeat pregnancies among adolescents who seek hormonal contraception. This study has strong implications for reproductive health policy, especially as directed toward high-risk teenage populations.

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Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.

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OBJECTIVE To assess patients' outcomes after subacromial or glenohumeral injections based on the degree of lateral extension of the acromion. METHODS 307 patients were prospectively included after therapeutic fluoroscopy-guided subacromial (n = 148) or glenohumeral (n = 159) injections with anaesthetic and long-acting corticosteroids. Pre- and post-injection outcomes at 1 week and 1 month were obtained using the 11-point numerical rating scale (NRS) for pain. Lateral extension of the acromion was quantified and categorized by the critical shoulder angle (CSA) and the acromion index (AI) on anteroposterior conventional radiographs. RESULTS Patients' outcomes at 1 week and 1 month were significantly improved (p < 0.001) compared to baseline for subacromial and glenohumeral injection patients. Patients with a CSA <35° showed significantly higher pain reduction 1 month after subacromial injection compared to patients with a CSA >35° (4.2 ± 2.6 vs. 3.2 ± 3.0, p = 0.04). A significant difference in the 1-month NRS change in pain scores is noted for smaller AIs after subacromial injection (4.3 ± 2.8 vs. 2.6 ± 2.9; p = 0.01). No significant association was noted between clinical outcome and the lateral extension of the acromion after glenohumeral joint injections. CONCLUSIONS A short lateral extension of the acromion was associated with better clinical outcomes in subacromial injection patients but not in glenohumeral injection patients. KEY POINTS • Patients' outcomes at 1 month improved significantly compared to baseline for subacromial injections. • Patients' outcomes at 1 month improved significantly compared to baseline for glenohumeral injections. • Short acromial lateralization was associated with better clinical outcome after subacromial injection. • The acromial lateralization was not associated with clinical outcome after glenohumeral injection.