Adherence to antiretroviral therapy and viral suppression: Analysis of three periods between 2011 and 2017 at an HIV-AIDS center, Brazil.

The increased effectiveness of antiretroviral therapy (ART) in the last 30 years is a scientific landmark, and viral suppression is directly associated with treatment adherence. The aim of this study was to compare the results of ART adherence and viral load suppression with the evolution of the protocols and other associated factors, in people living with HIV. A panel analysis of three descriptive longitudinal studies investigating ART adherence and viral load suppression was conducted in people with HIV treated at a drug dispensing unit in the Federal District. The studies were carried out during periods of 2011, 2013, and 2017, coinciding with the three different recommended treatment schemes for the country. Adherence was assessed using drug dispensing records. Viral load data were obtained from the Ministry of Health's Laboratory Examination Information System. Analysis of the data of 522 individuals in the three periods showed sociodemographic differences such as a decline in the percentage of women (from 33% in period 1 to 4% in period 3) and an increase in the percentage of young people. ART adherence was higher in period 2 (tenofovir/lamivudine/efavirenz scheme). Viral load suppression was greater in period 3 (tenofovir/lamivudine/dolutegravir scheme). The relative detectable viral load risk was nearly two-fold higher (RR 1.83) in people living with HIV with less than 80% adherence when compared to those above 80%. With respect to the different schemes recommended in Brazil during the periods studied, ART containing dolutegravir was the most effective in achieving viral load suppression. By contrast, there was better ART adherence in the daily combined fixed dose consisting of tenofovir/lamivudine/efavirenz in tablet form. Adherence to ART above 80% seemed to be enough to promote an effective treatment in therapeutic schemes including efavirenz or dolutegravir.

DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy.

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.

Neuronal and astrocytic tetraploidy is increased in drug-resistant epilepsy.

AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

INTRODUCTION: Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice. OBJECTIVE: To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication. METHODS: Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available. RESULTS: 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy. CONCLUSION: The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.

Pharmacokinetic variability of eslicarbazepine in real clinical practice.

INTRODUCTION: Eslicarbazepine acetate (ESL) is a sodium channel blocker indicated for partial-onset seizures with or without secondary generalization, at a single daily dose. There are very few publications on the levels of ESL metabolites in real clinical practice. OBJECTIVE: To describe the serum levels of licarbazepine (main metabolite of ESL) in patients with refractory epilepsy in real clinical practice. To evaluate the influence of age, sex, and polytherapy on levels and adverse effects. METHODS: This study involved a retrospective analysis of patients diagnosed with epilepsy treated with ESL for whom plasma levels of licarbazepine were available, measured by spectrophotometry. RESULTS: Sixty-four patients were included. One patient had licarbazepine levels of 0 (admitted not taking the drug) was not analyzed. Mean licarbazepine levels of 7.66 µg/mL (400 mg/day dose), 16.56 µg/mL (800-mg dose), and 20.80 µg/mL (1200 mg) were significantly different. There was a significant correlation between daily dose and serum levels (p < 0.05) and between the concentration/dose ratio and lower to higher doses (p < 0.05). Pharmacokinetic variability (coefficient of variation for the concentration/dose ratio) was 33.2%. We found a decrease in the concentration/dose ratio in the 1200 mg/day dose, compared to lower doses. We did not find differences by sex or intake of other antiepileptic inducers or metabolic inhibitors. Fifteen patients (23.8%) had mild nonsymptomatic hyponatremia. CONCLUSION: These results suggest that it is not necessary to routinely determine licarbazepine levels. In specific cases, licarbazepine levels can be useful to assess adherence to treatment and for personalized dose adjustment.

Predictors of perfusion computed tomography alterations in stroke mimics attended as stroke code.

BACKGROUND AND PURPOSE: Stroke mimics (SMs) account for a significant number of patients attended as stroke code (SC) with an increasing number over the years. Recent studies show perfusion computed tomography (PCT) alterations in some SMs, especially in seizures. The objective of our study was to evaluate the clinical characteristics and PCT alterations in SMs attended as SC in order to identify potential predictors of PCT alterations in SMs. METHODS: A retrospective study was performed including all SC activations undergoing a multimodal CT study including non-enhanced computed tomography (CT), CT angiography and PCT, as part of our SC protocol, over 39 months. Patients with a final diagnosis of SM after complete diagnosis work-up were therefore selected. Clinical variables, diagnosis, PCT alteration patterns and type of map affected (Tmax or time to peak, cerebral blood flow and cerebral blood volume) were registered. RESULTS: Stroke mimics represent up to 16% (284/1761) of SCs with a complete multimodal study according to our series. Amongst SMs, 26% (74/284) showed PCT alterations. PCT abnormalities are more prevalent in seizures and status epilepticus and the main pattern is alteration of the time to peak map, of unilateral hemispheric distribution or of non-vascular territory. In our series, the independent predictors of alteration in PCT in SMs are aphasia, female sex and older age. CONCLUSIONS: Perfusion computed tomography alterations can be found amongst almost a third of SMs attended as SC, especially older women presenting with aphasia with a final diagnosis of epileptic seizures and status epilepticus.

Zinc phthalocyanine tetrasulfonate-loaded polyelectrolytic PLGA nanoparticles for photodynamic therapy applications.

BACKGROUND: Photodynamic Therapy (PDT) is a modality for the treatment of neoplastic tissues, which is based on the administration of a phototherapeutic agent and light irradiation at an appropriate wavelength, aiming to locate and destroy the target cell with the formation of reactive oxygen species. Nanoencapsulation technology presents itself as a tool for incorporation of bioactive substances aiming to improve their solubility in physiological environment, obtain a longer circulation time in the organism, administration of lower dosages and the minimization of side effects. The present work aimed at the development of poly (lactic acid-glycolic acid) (PLGA) nanoparticles coated with polyelectrolyte film layers for encapsulating zinc phthalocyanine tetrasulfonated (ZnPcSO4) as a bioactive substance model. METHODS: PLGA nanoparticles were produced by the double emulsion/solvent evaporation technique and polyelectrolytic coating was performed using polyalkylamine hydrochloride (PAH) as a weak polycation and poly (4-styrene sulfonate) (PSS) as a strong polyanion by layer-by-layer self-assembly technique (known as layer-by-layer-LbL). The nanoparticulate system was studied by scanning electron microscopy, steady-state, and their biological activity was evaluated using in vitro cancer cell lines by classical MTT assay. RESULTS: The polyelectrolytic PLGA nanoparticles had an average diameter of 384.7 ± 138.6 nm, restricted distribution size with a polydispersity index. The obvious change in zeta potential indicates successful alternation in polycation (PAH) and polyanion (PSS) deposition directly in PLGA nanoparticles. Scanning electron microscopy (SEM) analysis showed that the formed system had morphology spherical, typical of these release systems. The loading efficiency was 82.1 % ± 1.2 %. The polyelectrolytic nanoparticles loaded with phthalocyanine maintained their photophysical behavior after encapsulation. Cell viability was determined, obtaining 90 % cell death. CONCLUSIONS: Therefore, the presented work depicts ZnPcSO4-loaded polyelectrolytic PLGA nanoparticles as a promise drug delivery system for phototherapeutic agent, which are thus expected to have superior therapeutic efficiency than free drug.

Feasibility of De-Escalation Implementation for Positive Blood Cultures in Patients With Sepsis: A Prospective Cohort Study.

Purpose: The aim of the present study was to determine whether de-escalation guided by blood cultures for patients with a diagnosis of sepsis, severe sepsis or septic shock reduces mortality, and antimicrobial drug resistance (ADR). Methods: A prospective, single-center, cohort study was conducted with adults admitted to the ICU with a diagnosis of sepsis, severe sepsis, or septic shock at a public hospital in Sorocaba, State of São Paulo, Brazil, from January 2013 to December 2013. We excluded patients who had negative blood cultures. Patients who had replaced the initial empirical broad-spectrum antibiotic therapy (EAT) by the antibiotic therapy guided by blood cultures were compared with those who continued receiving EAT. The outcome included mortality and antimicrobial drug resistance. We used the Cox regression (proportional hazards regression) and the Poisson regression to analyze the association between antibiotic therapy guided by blood cultures (ATGBC) and outcomes. The statistical adjustment in all models included the following variables: sex, age, APACHE II (Acute Physiology And Chronic Health Evaluation II) score and SOFA (Sequential Organ Failure Assessment) score. Results: Among the 686 patients who were admitted to the intensive care unit, 91 were included in this study. The mean age of the patients was 52.7 years (standard deviation = 18.5 years) and 70.3% were male. EAT was replaced by ATGBC in 33 patients (36.3%) while 58 patients (63.7%) continued receiving EAT. Overall hospital mortality decreased from 56.9% in patients who received EAT to 48.5% in patients who received ATGBC [Hazard ratio- HR 0.44 (95% CI 0.24-0.82), p = 0.009]. There was no association between ATGBC and ADR [HR 0.90 (95% CI 0.78 - 1.03) p = 0.15]. Conclusions: Although the early and appropriate empirical EAT is undoubtedly an important factor prognostic, ATGBC can reduce the mortality in these patients.

The Use of Assessment of Chronic Illness Care Technology to Evaluate the Institutional Capacity for HIV/AIDS Management.

The effectiveness of antiretroviral therapy has rendered HIV infection a manageable chronic condition. Currently, the health systems face the challenge of adopting organizational healthcare models capable of ensuring the delivery of comprehensive care. The Chronic Care Model has been reported for its effectiveness, particularly in terms of delivery system design. In this study, the Assessment of Chronic Illness Care (ACIC) questionnaire, a soft technology widely used for other chronic conditions, was employed on a teaching hospital to evaluate healthcare provided to people living with HIV/AIDS. The ACIC technology is a self-explanatory instrument which diagnoses, among the six components of the Chronic Care Model Framework, areas for quality improvements, indicating at the same time, intervention strategies and achievements. These components are healthcare network organization, delivery system design, self-management support, decision support, clinical information systems, and community. From May to October 2014, the tool was applied to the multidisciplinary teamwork at the points of care identified, as well as to the hospital management board. Respondents broadly rated care as basic. A pronounced contrast was observed from evaluation by management board and health professional staff in some components like organization of healthcare and clinical information system. The self-management support and delivery system design were the components best evaluated by the multidisciplinary team. Combined with the array of services offered, the entry points available at the hospital can ensure healthcare comprehensiveness. However, some gaps were detected, precluding the delivery of an effective care. The ACIC was considered an adequate technology to provide knowledge of the gaps, to promote productive discussions and reflections within teams and to indicate actions to achieve improvements on healthcare for people living with HIV/AIDS.

Evaluation of Pharmaceutical Services in Public Hospital Pharmacies of Federal District - Brazil.

OBJECTIVE: To evaluate pharmaceutical services in public hospital pharmacies of  the Federal District Health Department - Brazil (Secretaria de Saúde do Distrito  Federal, SES-DF). METHOD: A cross-sectional evaluative study involving the 15 public hospitals under the SES-DF management. Hospitals were characterized and classified into four hierarchical strata. The pharmaceutical services related  to programming (quantity of medication to order), acquisition, storage,  distribution, management, selection, information, pharmacotechnical  component, pharmacotherapy follow-up, teaching and research were evaluated  using validated indicators. Next, algorithms were applied and the approximation percentages of service compliance were calculated, then  correlated to variables that could influence their results through linear regression analysis. RESULTS: Only four hospital pharmacies presented good compliance with the  evaluated services, three of them belonging to less complex hospitals. Only the  storage and management services presented good performance. The variables  that most influenced the performance of the services were managerial aspects  related to pharmacists and non pharmacists' workload per bed, the existence of  a program for human resources qualification, planning goals and targets and a  manual of norms and procedures, as well as professional qualification and  adequacy of the area in which the services were performed (p < 0.01). CONCLUSIONS: The evaluated hospital pharmacies had average performance for  services compared to the ideal and better performance in logistics activities.  Pharmaceutical services require constant evaluation for rational interventions  that increase the proportion of executed health care activities and local  management capacity to make such actions more effective, efficient, qualified  and safe in the context of the SES-DF hospital network.

Objetivo: Evaluar los servicios farmacéuticos en farmacias públicas de hospitales del Departamento de Salud del Distrito Federal ­ Brasil (Secretaria de Saúde do Distrito Federal, SES-DF).Método: Estudio transversal evaluativo de los 15 hospitales públicos bajo  gestión de la SES-DF. Los hospitales fueron caracterizados y se clasificaron en  cuatro estratos jerárquicos. Los servicios de programación, adquisición, almacenamiento, distribución, gestión, selección, información, farmacotécnica, seguimiento farmacoterapéutico, enseñanza y  investigación fueron evaluados utilizando indicadores validados. Se aplicaron  algoritmos y se calcularon los porcentajes de aproximación del cumplimiento del  servicio, que se correlacionaron con variables que podrían influir en los  resultados a través de la regresión lineal.Resultados: Solo cuatro farmacias hospitalarias presentaron un buen cumplimiento de los servicios evaluados; tres pertenecientes a hospitales menos complejos. Solo el almacenamiento y la gestión presentaron  un buen desempeño. Las variables que más influyeron en el desempeño de los  servicios fueron la carga de trabajo de farmacéuticos y no farmacéuticos por  cama; la existencia de un programa de cualificación de recursos humanos,  objetivos y metas; el manual de normas y procedimientos, y la cualificación  profesional y la adecuación del área de ejecución de los servicios (p < 0,01).Conclusiones: Las farmacias hospitalarias evaluadas presentaron un cumplimiento medio de los servicios en comparación con el ideal y el mejor desempeño de las actividades logísticas. Los servicios farmacéuticos requieren una evaluación constante con vistas a intervenciones  racionales que amplíen la ejecución de las actividades asistenciales y la  capacidad de gestión local con el objetivo de hacer tales acciones más efectivas, eficientes, cualificadas y seguras.

When aphasia is due to aphasic status epilepticus: a diagnostic challenge.

Aphasic status epilepticus is an uncommon entity that should be included in the differential diagnosis of persistent and sudden language disorders. In our study, we describe seven patients admitted with clinical and electroencephalographic diagnosis of aphasic status, who were studied with both neuroimaging and electroencephalogram. The mean age was 65.9 years (range of 39-89). Three of the patients had previously been diagnosed of epilepsy. The aphasia was global in six patients. In one case, we found foci of the left hemorrhagic contusions. The initial electroencephalogram (EEG) was not conclusive of status in two patients. In one patient, neuroimaging showed left hemispheric hypoperfusion, compatible with postictal changes. Six out of seven patients required at least two antiepileptic drugs. Three patients died of systemic complications (infectious causes), whereas the other four cases had a complete recovery. Our study highlights that a second EEG study might be necessary to confirm epileptiform activity, when clinical features and other tests suggest an epileptic origin. An early and specific treatment, avoiding or diminishing comorbidities, might significantly improve the prognosis of these patients.

Do people with epilepsy have a different lifestyle?

BACKGROUND: Epilepsy is one of the most common neurological diseases. Its high prevalence, economic relevance and impact on daily life make it crucial that we study this condition in further detail. Our study seeks to investigate whether the lifestyle of people diagnosed with epilepsy is different to that of people without epilepsy, in order to better understand our patients. METHODS: We designed and delivered a questionnaire about quality of life and daily habits to patients from our hospital's Epilepsy Unit. We also delivered the questionnaire to a control group with similar demographic characteristics. Lifestyle differences between patients and control group members were analyzed. Patients were further divided according to the type of epilepsy, time since diagnosis, seizure frequency and pharmacotherapy. RESULTS: A total of 278 people were interviewed (85 patients, 193 controls). There was no difference in educational level, marital status and healthy habits (sports, reading and diet) between the groups. However, patients with epilepsy were more often unemployed (p<0.05) and had a healthier lifestyle (lower body mass index, lower alcohol consumption and a tendency towards smoking less). Anxiolytic-antidepressant intake was higher in patients with epilepsy. In terms of the type of epilepsy, patients with focal epilepsy exercised more than those with generalized epilepsy; no other statistically significant differences were found between the individuals studied. DISCUSSION: Epilepsy diagnosis does not seem to negatively alter the daily life of patients; in fact, many adopt a healthier lifestyle after diagnosis. The risk of antidepressant/anxiolytic intake is, however, higher, which could reflect the impact this chronic condition still has at a social level.

Access to medicines for diabetes treatment in Brazil: evaluation of "health has no price" program.

BACKGROUND: In 2011, private pharmacies associated to the Brazilian Ministry of Health provided patients with two types of insulin (regular human insulin and isophane insulin or NPH) and three oral antidiabetic medications (5 mg glibenclamide and 500 and 850 mg metformin) free of charge. The aim was to evaluate the impact of the "Health Has No Price" Program [Saúde Não Tem Preço (SNTP)] for access to diabetes treatment medicines in Brazil. METHODS: This longitudinal and observational study is based on the number of units of oral hypoglycemic agents, insulin and insulin analogues supplied in 55,000 private pharmacies from February 1, 2010 to January 31, 2012. The number of tablets (oral hypoglycemic agents) and international units (insulins and insulin analogues) supplied in the first 12 months of the SNTP Program were compared with the number of tablets and international units supplied in the 12 months prior to its implementation. RESULTS: The insulins in the SNTP program had the highest percentage change in the number of international units supplied; regular human insulin increased by 97.8 % and isophane insulin (NPH) by 78.0 %. Among the oral hypoglycemic agents, 5 mg glibenclamide increased by 65.9 %, and 500 and 850 mg metformin increased by 46.8 and 39.9 %, respectively, in the number of tablets dispensed in the first year of the SNTP Program. Among the hypoglycemic agents not available in SNTP, 4 mg glimepiride had the highest percentage increase in units supplied (19.2 %) in the same period. Among the insulin analogues, which were not available in the SNTP Program, insulin glulisine showed the greatest increase in units dispensed (34.2 %). CONCLUSIONS: The SNTP Program contributed to increased access to medicines for the treatment of diabetes in Brazil.

Cytotoxic and genotoxic assessment of surface water from São Paulo State, Brazil, during the rainy and dry seasons.

The aim of this study was to determine if the cytotoxic and genotoxic responses of Allium cepa are effective biomarkers of harmful effects caused by polluted river water and if changes in the responses reflect seasonality in the harmful effects. Samples were collected in the dry season (August 2011 and 2012) and rainy season (February 2012 and 2013) at sampling points on the Jaguari River and the Ribeirão Lavapés, in Brazil. Allium cepa bulbs were exposed to the samples, to positive controls (15 µg/L methyl methanesulfonate), and to negative controls (tap water). Three root tips from each bulb were then stained using the Feulgen reaction, then the micronucleus frequency, the mitotic index, and mitotic anomalies were measured. The total number of anomalies (stickiness, c-mitosis, multipolarity, chromosome bridges, and unidentified anomalies) in the rainy season (8.61 ± 3.65) and dry season (7.07 ± 2.96) were significantly different (U = 11.31, p = 0.04). Toxicity, indicated by the formation of micronuclei and the mitotic index, was higher in the February 2012 samples than in the August 2012 samples. The mean manganese concentration (0.13 mg/L) in the rainy season samples was higher than the maximum concentration permitted by the Brazilian National Environmental Council (<0.1 mg/L) and the manganese concentrations positively correlated with chromosomal aberration induction (p = 0.01, r = 0.69). In conclusion, the rainy season samples were more toxic than the dry season samples. This was probably related to rain water carrying compounds with potentially negative impacts into the rivers. These findings highlight the importance of biomonitoring studies and of treating wastewater in urban areas.

[Laparoscopy for diagnosis and treatment of adnexal masses]. / Laparoscopia na abordagem inicial de tumores anexiais.

PURPOSE: To assess clinical factors, histopathologic diagnoses, operative time and differences in complication rates between women undergoing laparoscopy or laparotomy to diagnose and treat an adnexal mass and their association with laparoscopy failure. METHODS: In this prospective study, 210 women were invited to participate and 133 of them were included. Eighty-eight women underwent laparotomy and 45 underwent laparoscopy. Fourteen of the 45 laparoscopies were converted to laparotomy intraoperatively. We assessed whether age, body mass index (BMI), previous abdominal surgeries, CA-125, Index of Risk of Malignancy (IRM), tumor diameter, histological diagnosis, operative time and surgical complication rates differed between the laparoscopy group and the group converted to laparotomy and whether those factors were associated with conversion of laparoscopy to laparotomy. We also assessed surgical logs to evaluate the reasons, as stated by the surgeons, to convert a laparoscopy to laparotomy. RESULTS: In this research, 30% of the women had malignant tumors. CA-125, IRM, tumor diameter and operative times were higher for the laparotomy group than the laparoscopy group. Complication rates were similar for both groups and also for the successful laparoscopy and unsuccessful laparoscopy groups. The surgical complication rate in women with benign tumors was lower for the laparoscopy group than for the laparotomy group. The factors associated with conversion to laparotomy were tumor diameter and malignancy. During laparoscopy, adhesions a large tumor diameter were the principal causes of conversion. CONCLUSION: This study suggests that laparoscopy for the diagnosis and treatment of adnexal masses is safe and does not increase complication rates even in patients who need conversion to laparotomy. However, when doubt about the safety of the procedure and about the presence of malignancy persists, consultation with an expert gynecology-oncologist with experience in advanced laparoscopy is recommended. A large tumor diameter was associated with the necessity of conversion to laparotomy.

Cognitive but not affective theory of mind deficits in mild relapsing-remitting multiple sclerosis.

OBJECTIVE: We studied theory of mind (ToM) in patients with mild relapsing-remitting multiple sclerosis (MS), seeking possible dissociations between its 2 components: cognitive ToM (the ability to infer others' intentions) and affective ToM (the ability to infer others' emotional states). We analyzed the relationship of ToM to executive function, depression, and fatigue. BACKGROUND: Dissociations between cognitive and affective ToM have been found in several neurologic and neuropsychiatric diseases. Most ToM studies in patients with MS have shown general ToM deficits but have not analyzed the cognitive and affective aspects individually. METHODS: We used the Faux Pas test of ToM and tests of executive function to assess 18 patients with mild relapsing-remitting MS and 16 control participants. RESULTS: Our patients showed deficits in cognitive ToM, but their affective ToM seemed to be spared. Their cognitive ToM deficits were not related to executive dysfunction, depression, or fatigue. CONCLUSIONS: Our study is the first differential analysis showing cognitive but not affective ToM deficits in mild relapsing-remitting MS. Further research is needed to determine the exact nature and the real impact of these deficits, and to establish their relationship with the neuropathology and progression of MS.

Familial benign frontotemporal deterioration with C9ORF72 hexanucleotide expansion.

BACKGROUND: In recent years, a benign variant of frontotemporal lobar degeneration (FTLD) has been recognized, with a particularly slow progression of cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in neuroimaging studies. Patients with FTLD have been considered "phenocopies," with an underlying nondegenerative neurologic process. RESULTS: We report the first family with three affected members having benign FTLD associated with C9ORF72 gene hexanucleotide expansion. Onset of symptoms occurred during the fifth decade, with naming and memory problems as the main features. Two siblings have stabilized at mild cognitive impairment or incipient dementia for more than a decade, and remain quite independent for their activities of daily living at the current ages of 69 and 65 years, respectively. Their mother's cognitive deterioration evolved slowly during >30 years. CONCLUSION: This family demonstrates that a benign evolution can be part of the growing spectrum of clinical phenotypes associated with neurodegenerative diseases caused by the C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be considered in cases with this slow deterioration, especially if there is a family history.

Analysis of the contribution of immunologically-detectable HER2, steroid receptors and of the "triple-negative" tumor status to disease-free and overall survival of women with epithelial ovarian cancer.

We assessed associations between steroid receptors including: estrogen-alpha, estrogen-beta, androgen receptor, progesterone receptor, the HER2 status and triple-negative epithelial ovarian cancer (ERα-/PR-/HER2-; TNEOC) status and survival in women with epithelial ovarian cancer. The study included 152 women with primary epithelial ovarian cancer. The status of steroid receptor and HER2 was determined by immunohistochemistry. Disease-free and overall survival were calculated and compared with steroid receptor and HER2 status as well as clinicopathological features using the Cox Proportional Hazards model. A mean follow-up period of 43.6 months (interquartile range=41.4 months) was achieved where 44% of patients had serous tumor, followed by mucinous (23%), endometrioid (9%), mixed (9%), undifferentiated (8.5%) and clear cell tumors (5.3%). ER-alpha staining was associated with grade II-III tumors. Progesterone receptor staining was positively associated with a Body Mass Index≥25. Androgen receptor positivity was higher in serous tumors. In stand-alone analysis of receptor contribution to survival, estrogen-alpha positivity was associated with greater disease-free survival. However, there was no significant association between steroid receptor expression, HER2 status, or TNEOC status, and overall survival. Although estrogen-alpha, androgen receptor, progesterone receptor and the HER2 status were associated with key clinical features of the women and pathological characteristics of the tumors, these associations were not implicated in survival. Interestingly, women with TNEOC seem to fare the same way as their counterparts with non-TNEOC.