Difficulties reported by HIV-infected patients using antiretroviral therapy in Brazil

OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment. INTRODUCTION: Patients perceptions about their treatment are a determinant factor for improved adherence and a better quality of life. METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis. RESULTS: Among 406 patients initiating treatment, 350 (86.2%) and 209 (51.5%) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4% and 37.3% on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm3) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit. CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.     

Targeting gonadotropins: an alternative option for Alzheimer disease treatment

Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of the disease. As such, the role of reproductive hormones, which are closely associated with the cell cycle both during development and after birth, may be of key import. While estrogen has been the primary focus, the protective effects of hormone replacement therapy on cognition and dementia only during a crucial period led us to expand the study of hormonal influences to other members of the hypothalamic pituitary axis. Specifically, in this review, we focus on luteinizing hormone, which is not only increased in the sera of patients with Alzheimer disease but, like estrogen, is modulated by hormone replacement therapy and also influences cognitive behavior and pathogenic processing in animal models of the disease. Targeting gonadotropins may be a useful treatment strategy for disease targeting multiple pleiotropic downstream consequences.     

Poly(hydroxyethyl methacrylate-co-methacrylated-beta-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties

Copolymerization of hydroxyethyl methacrylate (HEMA) with a methacrylated-derivative of β-cyclodextrin (β-CD) was evaluated as a way to obtain hydrogels with tunable mechanical and drug loading and release properties, particularly for preparing medicated soft contact lenses. A fully methacrylated β-CD monomer was synthesized and added to the HEMA and cross-linker solution at concentrations ranging from 0.042 to 0.333 g ml⁻¹ (i.e. 0.23–1.82 mol.%). Thermal polymerization led to transparent hydrogels with a degree of conversion above 74%, which showed a high cytocompatibility and did not induce macrophage response. The greater the content in methacrylated β-CD was, the higher the glass transition temperature, the lower the degree of swelling and free water proportion, and the greater the storage and loss moduli of the swollen disks. These findings are directly related to the increase in the degree of cross-linking caused by the methacrylated β-CD. Loading studies were carried out with hydrocortisone and acetazolamide, both able to form complexes with CDs in water and in lacrimal fluid. Hydrocortisone loading progressively decreased as the content in methacrylated β-CD rose due to a decrease in the volume of aqueous phase of the hydrogel. Acetazolamide loading showed a maximum for an intermediate content in β-CD (0.125–0.167 g ml⁻¹) owing to a balance between complexation with β-CD and hydrogel mesh size. The hydrogels sustained drug delivery for several days, the acetazolamide release rate being dependent on the β-CD content. An adequate selection of the content in β-CD enables pHEMA-co-β-CD hydrogels suitable for specific biomedical applications to be obtained.     

A meta-analysis of resuscitative endovascular balloon occlusion of the aorta (REBOA) or open aortic cross-clamping by resuscitative thoracotomy in non-compressible torso hemorrhage patients

Background

The objective of this systematic review and meta-analysis was to determine the effect of REBOA, compared to resuscitative thoracotomy, on mortality and among non-compressible torso hemorrhage trauma patients.

Methods

Relevant articles were identified by a literature search in MEDLINE and EMBASE. We included studies involving trauma patients suffering non-compressible torso hemorrhage. Studies were eligible if they evaluated REBOA and compared it to resuscitative thoracotomy. Two investigators independently assessed articles for inclusion and exclusion criteria and selected studies for final analysis. We conducted meta-analysis using random effect models.

Results

We included three studies in our systematic review. These studies included a total of 1276 patients. An initial analysis found that although lower in REBOA-treated patients, the odds of mortality did not differ between the compared groups (OR 0.42; 95% CI 0.17–1.03). Sensitivity analysis showed that the risk of mortality was significantly lower among patients who underwent REBOA, compared to those who underwent resuscitative thoracotomy (RT) (RR 0.81; 95% CI 0.68–0.97).

Conclusion

Our meta-analysis, mainly from observational data, suggests a positive effect of REBOA on mortality among non-compressible torso hemorrhage patients. However, these results deserve further investigation.

     

Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression

BackgroundKetamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor–dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.MethodsResting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.ResultsA reduction in Montgomery–Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.ConclusionsThese preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.     

Control of hypertension with medication: a comparative analysis of national surveys in 20 countries

Objective

To examine hypertension management across countries and over time using consistent and comparable methods.

Methods

A systematic search identified nationally representative health examination surveys from 20 countries containing data from 1980 to 2011 on blood pressure measurements, the diagnosis and treatment of hypertension and its control with antihypertensive drugs. For each country, the prevalence of hypertension (i.e. systolic blood pressure ≥ 140 mmHg or antihypertensive use) and the proportion of hypertensive individuals whose condition was diagnosed, treated or controlled with medications (i.e. systolic pressure < 140 mmHg) were estimated.

Findings

The age-standardized prevalence of hypertension varied between countries: for individuals aged 35 to 49 years, it ranged from around 12% in Bangladesh, Egypt and Thailand to around 30% in Armenia, Lesotho and Ukraine; for those aged 35 to 84 years, it ranged from 20% in Bangladesh to more than 40% in Germany, the Russian Federation and Turkey. The age-standardized percentage of hypertensive individuals whose condition was diagnosed, treated or controlled was highest in the United States of America: for those aged 35 to 49 years, it was 84%, 77% and 56%, respectively. Percentages were especially low in Albania, Armenia, the Islamic Republic of Iran and Turkey. Although recent trends in prevalence differed in England, Japan and the United States, treatment coverage and hypertension control improved over time, particularly in England.

Conclusion

Globally the proportion of hypertensive individuals whose condition is treated or controlled with medication remains low. Greater efforts are needed to improve hypertension control, which would reduce the burden of noncommunicable diseases.     

Onchocerciasis in Ecuador,IV. Comparative studies of the disease relating to the Chachi and Black populations in the province of Esmeraldas

The frequency, intensity and clinical features of onchocerciasis in the two ethnic groups (Blacks and Chachilla—an indigenous tribe) in the endemic foci of the disease in Esmeraldas province (Ecuador) were evaluated. The incidence of infection and intensity of the disease seen in both groups were directly related to the frequency of man-vector contact and not to racial factors. Both groups showed the same rate of positivity in both the hyperendemic and hypoendemic areas. Males of both groups had a consistently higher positivity rate than did females. The Chachilla were found to have a higher mean microfilarial density than Blacks in both types of endemic areas. Certain clinical features of the disease analogous to those seen in the African form were present only in Blacks. No lymphatic involvement or hypertrophic scarring was seen in the Chachilla, suggesting that in the Blacks there may be a generaically related predisposition to lymphatic complications of microfilarial infections.     

Systemic synergism between codeine and morphine in three pain models in mice

BackgroundThe combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes.MethodsThis study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models.ResultsIntrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip).ConclusionThis synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.     

Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes.

Apoptosis may be a major event in chemical-induced injury, and therefore the detection of apoptotic effects when developing new drugs is highly relevant in screening for pharmacotoxicological risk assessment. However, as apoptosis in vitro normally degenerates to secondary necrosis, it is possible that it is underestimated, unless sensitive and specific parameters are used. In this present study we have evaluated the usefulness of a set of markers associated with the pivotal steps in the execution phase of apoptosis, in order to detect apoptotic compounds in hepatocytes before significant necrosis takes place. The markers selected include several biochemical parameters (downregulation of the antiapoptotic bclX(L) gene, caspase-3 activation, and cytochrome C release from mitochondria), and flow cytometry determinations (analysis of the size of the nuclei, chromatin complexity, and DNA integrity). The effects of several well-known model apoptotic toxicants (galactosamine, tertiary-butyl-hydroperoxide, etoposide, campothecine, and curcumin) were analyzed in hepatocytes. The aim was to identify early markers of apoptosis using known inducers of apoptosis in hepatocytes, as this battery of markers is designed to identify compounds triggering apoptosis in hepatocytes prior to necrosis. Concentrations of the compounds, as low as possible in order to keep 90% of hepatocyte viability, were selected according to their intracellular lactate dehydrogenase (LDH) leakage, which is well known as an indicator of cell membrane integrity and cell viability. The results demonstrated that (1) the apoptotic effect of 4 out of 5 compounds could be detected in low concentrations of the drugs long before cell necrosis (tertiary-butyl-hydroperoxide-induced apoptosis was only detected at concentrations causing concomitant necrosis) and (2) among the markers evaluated, caspase 3 activation and nucleus and DNA analysis by flow cytometry were used to fulfil the compromise between reliability, sensitivity, and ease of performance, which are critical issues when screening for an apoptotic effect of newly developed drugs.