Neurotoxicity of crack cocaine exposure: evidence from a systematic review of in vitro and in vivo studies.

Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.

Prenatal caffeine consumption and neurobehavioral disorders - A systematic review.

Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review was conducted to investigate the association between prenatal caffeine exposure and neurobehavioral disorders. The MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS databases were searched. Observational studies involving women with documented caffeine consumption during pregnancy were eligible for inclusion. The outcomes evaluated were behavioral and intellectual development, Attention Deficit Hyperactivity Disorder, and related behaviors. The data were analyzed by qualitative synthesis. The ROBINS-I tool was employed to assess the risk of bias, and the certainty of evidence was evaluated using GRADE (PROSPERO: CRD42023421164). The search yielded fourteen studies that met the inclusion/exclusion criteria. The sample size among pregnant women ranged from 173 to 64,189, and among children ranged from 88 to 49,190. Maternal caffeine consumption during pregnancy ranged from 0 to 1000 mg/day, with the highest levels observed during mid-pregnancy. Seven studies indicated a potential association between prenatal caffeine exposure and neurobehavioral/neurodevelopment deficits, one study showed that prenatal caffeine exposure improved peer problems, and six studies did not show a significant effect of prenatal caffeine consumption on neurobehavioral disorders. The included studies were classified as moderate for the risk of bias and with very low certainty of evidence. Thus, the evidence is insufficient to confirm with certainty that the prenatal caffeine exposure leads to neurobehavioral disorders. Studies heterogenicity, as well as their variable quality and the presence of several confounding factors, generate uncertainty.

Effectiveness of epidural morphine for the treatment of cancer pain in patients with gastrointestinal neoplasm-a systematic review.

One-third of cancer pain patients do not experience adequate pain relief using analgesic ladder by the World Health Organization. Interventional procedures, such as epidural morphine, have been considered. This study aimed to review the literature comparing the effects of epidural administration of morphine with the oral route. This systematic review included randomized controlled trials (RCTs) conducted with patients with gastrointestinal neoplasm. A search was conducted on PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and CINAHL databases to identify studies published up to May 2023. The retrieved study was evaluated using the Risk of Bias 2 (RoB 2) tool and qualitatively synthesized. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach (Prospero: CRD42021264728). Only one RCT, a crossover trial, was included in this systematic review. The study was conducted with ten participants (one withdrawal) and reported a statistically significant difference between both subcutaneous and epidural morphine solutions and oral morphine. The adverse events were not described. The included study presents some concerns of bias and low certainty of evidence on the effectiveness and security of epidural morphine administration. The available literature does not suffice to elucidate whether morphine administration via the epidural route is more effective than other routes. Further RCTs are necessary to improve the level of evidence on the effectiveness and risk-benefit of epidural morphine in the management of cancer pain in gastrointestinal neoplasm patients.

Availability of emergency contraception in large Brazilian municipalities: a guaranteed right?

Introduction: Emergency Contraception (EC) is available in Brazil since 1996, when it was adopted as one if the family planning strategies and, in 1998, for use in services assisting victims of sexual violence. In the country, its use is regulated by guidelines. Its access through SUS (Unified Health System), however, does not seem to occur in a standardized manner. Methods: The aim of the study was to analyze the availability and barriers to accessing emergency contraception (levonorgestrel) in Brazilian municipalities with more than 500 thousand inhabitants. The survey was carried out by a form sent to the Municipal Health Departments (SMS) managers and a search on the list of standardized medicines by the hospitals in the same municipalities. Results: The Basic Health Units were identified as the standard access places to EC. However, one of the obstacles mentioned is the need for a prescription for dispensing in almost 80% of the analyzed cities. Access in emergency situations at night and on weekends is also uncertain, since although 67% of the places stated that they dispense at the hospital level, the item was only standardized in 21% of the hospital lists. Discussion: The difficult access this drug in the public system essentially tends to harm the poorest women, who are the ones who suffer most from the consequences of an unwanted pregnancy.

Gestational lead exposure and its effects on fetal/infant development - A systematic review.

Studies suggest that gestational exposure to lead (Pb) is related to spontaneous abortions, preterm birth, lower infant birth weight and length, and neurological dysfunctions. However, the evidence about its effects during pregnancy exposure on fetal and child development is still poor. Thus, the aim of this systematic review was to verify the association between prenatal exposure to Pb and the occurrence of neurobehavioral deficits, miscarriages, and child mortality. Observational studies with pregnant women exposed to Pb during pregnancy were included, without gender or ethnicity restrictions. The MEDLINE, Cochrane Library, EMBASE, Scopus, Web of Science, and LILACS databases were searched. The reading of titles and abstracts was conducted, followed by reading in full format and data extraction, that were performed independently by two reviewers. The included studies were evaluated by Downs and Black tool and qualitatively synthesized. Certainty of evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluations (GRADE). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022296750). Among twenty-one studies included, sixteen were classified as prospective cohort, two case-control, one nested case-control, one cohort, and one longitudinal study. No study that evaluated child mortality associated with gestational Pb exposure was found. There is a very low certainty of evidence in the association of gestational Pb exposure and neurobehavioral deficits or miscarriages. This systematic review reflects the poor evidence and the challenges of human toxicology studies, since it was not possible to associate gestational Pb exposure to neurobehavioral deficits, miscarriages, and child mortality.

Oral pregabalin is effective as preemptive analgesia in abdominal hysterectomy-A randomized controlled trial.

Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever-increasing relevance. Opioid-sparing strategies, such as multimodal analgesia, are trends in this scenario. Pregabalin is a well-established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double-blind, placebo-controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty-five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy.

Antimicrobial stewardship for surgical antibiotic prophylaxis and surgical site infections: a systematic review.

Background Surgical site infections account for 14-17% of all healthcare-associated infections. Antimicrobial stewardship (AMS) are complementary strategies developed to optimize the use of antimicrobials. Aim to evaluate the effectiveness of AMS in promoting adherence to surgical antibiotic prophylaxis protocols in hospitalized patients, reducing surgical site infection rate and cost-benefit ratio. Method This systematic review of randomized clinical trials, non-randomized clinical trials and before and after studies was performed using Pubmed, Cochrane, Web of Science, Scopus, Embase, Google Scholar and ClinicalTrials.gov, in addition to reference lists of included studies. The risk of bias of studies was measured by the ROBINS-I checklist and the quality of the evidence synthesis by GRADE. Results Fourteen before and after design studies were included. In 85.7% of the studies, AMS was effective in increasing adherence to surgical antibiotic prophylaxis protocols and in 28.5%, there was reduction in surgical site infection rate. Three studies evaluated cost-benefit ratio and found a favorable impact. Eight (57%) studies were at risk of moderate bias and six had severe bias. The evaluation of the synthesis of evidence showed quality ranging from low to very low. Conclusion AMS, such as audit, feedback, education, implementation of a protocol, and a computer-assisted decision support methodology, appear to be effective in promoting adherence to surgical antibiotic prophylaxis protocols, reducing surgical site infection rate with a positive economic impact. However, more studies, particularly randomized clinical trials, are needed to improve the level of evidence of available information on AMS in order to favor decision-making.

Caracterização do acesso a medicamentos em um município de médio porte no leste do estado de Minas Gerais, Brasil / Characterization of access to medicines in a medium-sized municipality in the east of Minas Gerais, Brazil

Apesar das dificuldades políticas e estruturais das décadas de 1980 e 1990, avanços significativos como a criação e a implementação do Sistema Único de Saúde e a publicação da Política Nacional de Medicamentos favoreceram o acesso a medicamentos no Brasil. Buscando compreender melhor este fenômeno, o presente estudo teve como objetivo caracterizar o acesso a medicamentos em um município de médio porte do leste do estado de Minas Gerais. Trata-se de um estudo transversal desenvolvido sob o modelo da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil - Componente Avaliação do Serviço de Assistência Farmacêutica Básica. Foram entrevistados os usuários do Sistema Único de Saúde, os responsáveis pela dispensação de medicamentos nas unidades públicas de saúde na Atenção Primária, médicos da rede pública, o responsável pela assistência farmacêutica do município e o representante do secretário municipal de Saúde. Os resultados evidenciaram que houve períodos de desabastecimento de medicamentos e insumos nos últimos 12 meses, provavelmente relacionados à ausência de uma Relação Municipal de Medicamentos Essenciais e Comissão de Farmácia Terapêutica, prescrição de medicamentos pelos nomes comerciais, redirecionamento dos recursos do Componente Básico da Assistência Farmacêutica, ausência de auxiliares para os responsáveis pela dispensação de medicamentos e aos dispendiosos recursos empregados na aquisição de medicamentos para atender demandas judiciais. Ações em gestão direcionadas para a correção das falhas apontadas devem ser realizadas para otimizar o empenho de recursos do município e, consequentemente, melhorar o acesso a medicamentos na atenção básica.

Despite the structural difficulties in public health in the 80's and 90's, there were significant advances in the Brazilian health system back then, like the creation of the Unified Health System and the National Medicine Policy. They seem to have favored access to medicines in Brazil. The present study aimed to characterize the access to medicines in a medium-sized municipality in the eastern state of Minas Gerais. This study is based on the evaluation component of the National Research on Access, Use and Promotion of the Rational Use of Medicines - Component Evaluation of the Basic Pharmaceutical Assistance Service. The users of the Unified Health System, those responsible for dispensing medications in public health units in Primary Care, public doctors, the person responsible for pharmaceutical assistance in the municipality, and the representative of the municipal health secretary were interviewed. The results showed that there were shortages of medicines and supplies in the last 12 months and probably they are related to: absence of a Municipal Drug List and Therapeutic Pharmacy Commission, prescription of medicines by trade names, redirection of the Basic Assistance Component Pharmaceutical funds, lack of auxiliaries for those responsible for dispensing drugs, and the excessive financial resources used in legal demands. Management actions that aim to correct the mentioned flaws, can help in the improvement of the health field, with the optimized commitment of resources and consequent complete attention to the needs of the users of the health system.