Adverse Psychological and Therapeutic Effects of Kratom (Mitragyna speciosa) Use: A Systematic Review

@#Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.

Bivalirudin vs heparin in cardiac-cerebral ischemic and bleeding events among Chinese STEMI patients during percutaneous coronary intervention: a retrospective cohort study

Although bivalirudin has been recently made available for purchase in China, large-scale analyses on the safety profile of bivalirudin among Chinese patients is lacking. Thus, this study aimed to compare the safety profile of bivalirudin and heparin as anticoagulants in Chinese ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). A total of 1063 STEMI patients undergoing PCI and receiving bivalirudin (n=424, bivalirudin group) or heparin (n=639, heparin group) as anticoagulants were retrospectively enrolled. The net adverse clinical events (NACEs) within 30 days after PCI were recorded, including major adverse cardiac and cerebral events (MACCEs) and bleeding events (bleeding academic research consortium (BARC) grades 2-5 (BARC 2-5)). The incidences of NACEs (10.1 vs 15.6%) (P=0.010), BARC 2-5 bleeding events (5.2 vs 10.3%) (P=0.003), and BARC grades 3-5 (BARC 3-5) bleeding events (2.1 vs 5.5%) (P=0.007) were lower in the bivalirudin group compared to the heparin group, whereas general MACCEs incidence (8.9 vs 6.4%) (P=0.131) and each category of MACCEs (all P>0.05) did not differ between two groups. Furthermore, the multivariate logistic analyses showed that bivalirudin (vs heparin) was independently correlated with lower risk of NACEs (OR=0.508, P=0.002), BARC 2-5 bleeding events (OR=0.403, P=0.001), and BARC 3-5 bleeding events (OR=0.452, P=0.042); other independent risk factors for NACEs, MACCEs, or BARC bleeding events included history of diabetes mellitus, emergency operation, multiple lesional vessels, stent length >33.0 mm, and higher CRUSADE score (all P<0.05). Thus, bivalirudin presented a better safety profile than heparin among Chinese STEMI patients undergoing PCI.

Prescripción de protectores gástricos en pacientes reumatológicos: análisis desde Consulta Externa de Gastroenterología / Prescription of gastric protectors in rheumatological patients: Analysis from a gastroenterology outpatient clinic

Introducción: Los antinflamatorios no esteroideos son los medicamentos más recetados por reumatólogos y traumatólogos. Pero a pesar de tener una eficacia similar para controlar la inflamación y el dolor, los diferentes antinflamatorios no esteroideos disponibles presentan variabilidad en su perfil de seguridad. Objetivo: Brindar una panorámica sobre la prescripción de protectores gástricos en pacientes reumatológicos, en dos centros hospitalarios, desde una perspectiva gastroenterológica. Métodos: La investigación se inscribe en el paradigma cuantitativo con un estudio observacional. Se conformaron dos grupos de pacientes, uno de ellos provenientes del hospital A y el segundo grupo pertenecía al hospital B. Discusión: Los gastroprotectores se han convertido en los fármacos de mayor demanda en las farmacias comunitarias de Ecuador, y los más prescritos son los inhibidores de la bomba de protones y en menor frecuencia los antihistamínicos H2. Respecto a los gastroprotectores más frecuentemente prescritos, según nuestro estudio, estos valores podrían obedecer a la disponibilidad y los costos de la famotidina y el omeprazol con respecto a otros medicamentos de probada eficacia (ansoprazol, pantoprazol, rabeprazol y ranitidina). Conclusiones: Durante los últimos años, el uso de los fármacos gastroprotectores en América Latina ha experimentado un importante desarrollo, con la observancia de normas y guías clínicas de manejo de casos que ofrecen recomendaciones importantes al respecto. Por tanto, desde una perspectiva gastroenterológica, para tener éxito, es indispensable procurar un conocimiento de estos aportes y evidencias científicas(AU)

Introduction: Nonsteroidal anti-inflammatory drugs are the most prescribed medications by rheumatologists and traumatologists. However, despite having similar efficacy in controlling inflammation and pain, the different available nonsteroidal anti-inflammatory drugs show variability in their safety profile. Objective: To provide an overview of the prescription of gastric protectors in rheumatological patients, in two hospital centers, from a gastroenterological perspective. Methods: The research is part of the quantitative paradigm with an observational study. Two groups of patients were formed, one of them from hospital A and the second group belonged to hospital B. Discussion: Gastroprotectors have become the drugs in greatest demand in community pharmacies in Ecuador, the most prescribed being Proton Pump Inhibitors (IBPS) and, to a lesser extent, H2 antihistamines (anti-H2). Regarding the most frequently prescribed gastroprotectors, according to our study, these values ​​could be due to the availability and costs of famotidine and omeprazole compared to other drugs with proven effectiveness, such as ansoprazol, pantoprazole, rabeprazole and ranitidine. Conclusions: In recent years, the use of gastroprotective drugs in Latin America has undergone significant development, with the observance of clinical case management norms and guidelines that offer important recommendations in this regard. Therefore, from a gastroenterological perspective, to be successful, it is essential to seek knowledge of these contributions and scientific evidence(AU)

Análisis de inmunogenicidad y perfil de seguridad de vacunas contra el SARS-CoV-2 en ensayos clínicos de fase I/II / Immunogenicity and safety profile analysis of SARS-CoV-2 vaccines in phase I/II clinical trials

The development of an effective vaccine against SARSCoV-2 has turned into a global priority in order to stop the advance of this ongoing COVID-19 pandemic. To date there are 25 candidate vaccines currently in a clinical trial stage, 3 of which have been subjected to phase I/II preliminary reports (ChAdOx1 nCoV-19, BNT162b1 and mRNA-1273). These vaccines have demonstrated to elicit robust cellular and humoral immune responses when compared to convalescent patients serum samples and have shown an acceptable safety profile with no reported severe side effects. Here we discuss the reported evidence regarding these vaccines.

The comparative effects of Itopride and Levosulpiride orally used in patients suffering from Non-ulcer dyspepsia

Background: Itopride and Levosulpiride both comes under the group of Prokinetic drugs. These drugs are used for the treatment of non-ulcer dyspepsia, heart burn, nausea and vomiting. Both drugs act on dopaminergic D2 receptor as antagonist and increases the concentration of acetylcholine so that gastric peristalsis will be increase and that time pressure at lower oesophageal sphincter will be increase thus gastric motility increases and there will be good gastro-duodenal co-ordination.Method: This study has to conduct on patients with complains of non-ulcer dyspepsia attended Medical outdoor and department of pharmacology of SKMCH Muzaffarpur, Bihar, India. The total 60 patients have to include in the study, which have to randomly divide in two groups. Group A (itopride) comprising of 30 patients and Group B (Levosulpiride) comprising of 30 patients. Patients have to randomly allocate to receive one tablet of itopride hydrochloride, 50 mg three times daily before meal and one tablet Levosulpiride of 75 mg three times daily before meal. Authors have to enroll the patients at the interval of two weeks and continue it upto 3 months.Results: Study did not found any remarkable change in biochemistry profile. Only QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Neither QT prolongation nor serious cardiac toxicity was observed with itopride hydrochloride therapy.Conclusions: In present study, efficacy of Itopride was comparable to Levosulpiride in relieving the symptoms of non-ulcer dyspepsia. Both the drugs were clinically and biochemically well tolerated. QT prolongation changes were found in two patients, but no serious cardiac toxicity was observed with patient receiving Levosulpiride. Itopride does not show cardiac toxicity and any changes in ECG.

Anticoagulación en enfermedad tromboembólica venosa / Anticoagulant therapy in venous thromboembolic disease

INTRODUCCIÓN: La enfermedad tromboembólica venosa está comprendida por la trombosis venosa profunda y el tromboembolismo pulmonar, las cuales son enfermedades comunes con alta morbilidad y mortalidad, incluso antes del diagnóstico. El tratamiento está basado principalmente en la terapia anticoagulante, con diferentes opciones dependiendo del ámbito clínico y la estabilidad del paciente (terapia oral vs parenteral). Objetivo: Revisar las diferentes opciones y escenarios clínicos para la indicación de terapia anticoagulante, basados en la evidencia médica actual. Metodología: Se realizó una búsqueda sistemática en las bases de datos PubMed, Scopus, Google Académico y Scielo sobre estudios que evaluaran la indicación de la terapia anticoagulante en pacientes con diagnóstico de enfermedad tromboembólica venosa, principalmente, estudios aleatorizados controlados y metaanálisis. Discusión y Resultados: Fueron encontrados estudios aleatorizados controlados donde se evidencian menores tasas de sangrado y recurrencia de la enfermedad tromboembólica venosa a favor de los anticoagulantes directos, excluyendo algunas situaciones especiales como cáncer y enfermedad renal crónica avanzada. Conclusión: La terapia anticoagulante es el pilar del tratamiento en la enfermedad tromboembólica, disminuyendo la morbilidad y mortalidad de esta entidad, aunque aumenta el riesgo de sangrado. Anteriormente, los anticoagulantes antagonistas de la vitamina K eran la única opción terapéutica, pero con altas tasas de sangrado, afortunadamente desde hace algunos años contamos con los anticoagulantes directos con mejores perfiles de seguridad y menor tasa de sangrado.

ABSTRACTS: Venous thromboembolic disease includes deep venous thrombosis and pulmonary embolism, which are common diseases with high morbidity and mortality. The treatment is based mainly on anticoagulant therapy, with different options depending on clinic context and patient stability (oral vs parenteral therapy). Objective: To review evidence based medical information regarding the use of anticoagulant therapy in venous thromboembolism. Methods: We performed a systematic review of PubMed, Scopus, Google scholar and Scielo databases, of randomized controlled studies and meta-analysis evaluating anticoagulant therapy in patients with thromboembolic venous disease. Results: Except for tromboembolic disease in patients with cancer or chronic kidney disease anticoagulation with direct (new) oral agents led to less bleeding episodes and lower relapse rate. Conclusion: anticoagulant therapy is the basis of treatment for thromboembolic disease, decreasing morbidity and mortality. New oral anticoagulants' are associated to better clinical results, notwithstanding a slight increase in bleeding episodes.

Need of the hour: pharmacovigilance study of SGLT-2 inhibitors

Background: Diabetes mellitus represents a global pandemic. Various pharmacotherapy and non-pharmacotherapy measures are advocated for its control. The latest in the pharmacotherapy are Sodium Glucose Transporter -2 (SGLT-2) inhibitors, widely used. Many studies suggest adverse effects related to SGLT-2 inhibitors, evidence still not conclusive and few data from India. Hence this study was planned.Methods: Cross-sectional study over a period of 02 months, recorded demographic details and history of various adverse drug reactions reported with the use of SGLT-2 inhibitors.Results: Majority of the study participants were females (58%) and belonged to the age group of 40-70 yrs. Urinary tract infections (UTI) and genital infections was more seen in the users of dapagliflozin, followed by empagliflozin and canagliflozin.Conclusions: SGLT-2 Inhibitors offer a unique therapeutic approach to the management of Diabetes Mellitus. Further evaluation of the safety profile and the risk-benefit analysis is the need of the hour.

Clinical safety profile of Premi-Rab a new indigenous equine rabies immunoglobulin for cat III animal bite victims at anti rabies clinic of a tertiary care hospital, Karnataka

Background: WHO guidelines recommend for treating Cat III animal bite victims with local infiltration of Equine Rabies Immunoglobulin (ERIG) into and around animal bite wounds followed by anti-rabies vaccine (ARV).The main reason for non-use of ERIGs by medical profession is the fear of anaphylaxis and laborious process. The present study was taken up with the objectives to assess the clinical safety of a new ERIG, describe sociodemographic profile of ERIG recipients and compliance to Intra Dermal Rabies Vaccine (IDRV), who reported to Anti Rabies Clinic (ARC) of Mandya Institute of Medical Sciences (MIMS), Mandya.Methods: Descriptive study at ARC, MIMS, Mandya for a period of one year. The data was collected using structured questionnaire. The data was entered into Microsoft excel and results were expressed using descriptive statistics.Results: The study revealed that cat III animal bite victims were 3400 (56.3%), of these only 545 (16.0%) opted for the new ERIG. Skin Sensitivity Test (SST) showed positive results in 17 (3.1%) cases. Among the ERIG recipients 28 (5.1%) had mild adverse reaction to ERIG. The compliance rate was 49.2% for all 4 doses of IDRV.Conclusions: 3.1% showed positive result to SST. 5.1% had mild adverse reaction to ERIG.

Studying activity and toxicity of different TNF-alpha inhibitors in controlling patients with active ulcerative colitis

Ulcerative colitis (UC) is a long-term disorder that associated with overactivation of immunoinflammatory system,ending with ulcer in the large intestine. This study aimed to compare the activity and toxicity of different TNF-alphainhibitors in a sample of Iraqi patients having active ulcerative colitis. Fifty patients with refractory ulcerative colitiswere randomly distributed to either group I (n = 25): on adalimumab injection (160/80 mg) or group II (n = 25): oninfliximab injection (5 mg/kg) along the term of induction. Clinical remission was considered as the primary subjectiveparameter, while clinical response, mucosal healing, and subscores of mild status were regarded as secondary subjectiveparameters. Fractional Mayo score, inflammatory bowel disease questionnaire (IBDQ), and safety profile were alsoevaluated. A 24% versus 28% patients were in clinical remission for those receiving adalimumab and infliximab,respectively (p > 0.05), while 48% versus 52% patients were in clinical response for those receiving adalimumab andinfliximab, respectively (p > 0.05), and 40% of patients acquired mucosal healing for both adalimumab and infliximabarms (p > 0.05). Scores of physician assessment and rectal bleeding was shown to be markedly higher in infliximabpatients (p < 0.05), while those of stool frequency was found to be higher in adalimumab patients (p < 0.05). Nosignificant difference was observed between two arms in the fractional Mayo score and IBDQ index (p > 0.05).Both of the studied biological agents were well-tolerated. As conclusion, the two different TNF-alpha inhibitors werecomparable in their clinical remission and safety profile for subjects with active ulcerative colitis.

Propuesta de lineamientos para los planes de manejo de riesgos de medicamentos en la República Bolivariana de Venezuela / Proposal of guidelines for medication risk management plans in the Bolivarian Republic of Venezuela

Los estudios clínicos realizados antes de la comercialización del producto farmacéutico y la Farmacovigilancia contribuyen al diseño del perfil de seguridad de un medicamento y a detectar posibles riesgos en la población consumidora, es por ello que en la actualidad autoridades regulatorias a nivel mundial exigen la presentación de Planes de Manejo de Riesgos de Medicamentos como requisito para su registro. El objetivo de esta investigación fue proponer lineamientos que puedan definir el cumplimiento de estos planes y el rol de la autoridad regulatoria para el seguimiento de los mismos, dicha propuesta estuvo enmarcada como un proyecto mixto, documental y factible. Se realizó un análisis comparativo de diferentes países que permitió detectar oportunidades de mejora sobre este tópico en Venezuela; con la finalidad de identificar aspectos importantes para realizar la propuesta de lineamientos, que será en pro de salvaguardar la salud de la población venezolana.

The clinical trials performed before of the commercialization of pharmaceuticals products and the Pharmacovigilance contribute to design of the safety profile of a medication and to detect possible risks in the consumer population, which is why today worldwide Regulatory Authorities require the submission of The Risk Management Plans of the medications as a requirement for registration. The objective of this research was to propose guidelines that can define the fulfillment of these plans and the role of the Regulatory Authority to monitor them, the proposal was framed as a mixed project, documentary and feasible. Was performed a comparative analysis of different countries which allowed to identify opportunities for improvement on this topic in Venezuela; in order to identify important aspects to the proposed guidelines, which will be in favor to safeguard the health of the Venezuelan population.

Pemetrexed and platinum as first-line chemotherapy for advanced lung adenocarcinoma:an observation of recent therapeutic effects and a safety profile / 中国肿瘤临床

Objective:The recent therapeutic effects and safety profile of pemetrexed plus cisplatin as first-line chemotherapy in advanced lung adenocarcinoma were evaluated. Methods:A total of 41 chemotherapy-naive locally advanced or metastatic non-small cell lung cancer patients, who were diagnosed with adenocarcinoma by pathological examination, were included. All patients received 500 mg/m2 pemetrexed on day 1. A total dose of 75 mg/m2 cisplatin was divided into three daily doses administered over 3 d. Treat-ments were repeated every three weeks. The therapeutic efficiency and safety profile were evaluated every two treatment cycles. Re-sults:All 41 patients were eligible for the evaluation of therapeutic efficiency. Seventeen patients showed partial response, 20 patients showed stable disease, and four patients showed disease progression. The overall response rate (ORR) was 41.5%and the disease con-trol rate (DCR) was 90.3%. Subgroup analysis showed that the ORR in males was significantly higher than that in females (63.1%vs. 22.7%, P=0.009). The median progression-free survival of all patients was 11.0 months, whereas the median overall survival was 12.6 months. The intracranial lesions of six patients with brain metastases were well controlled after chemotherapy and palliative whole brain radiotherapy. The ORR and DCR for these patients were 83.3%and 100.0%, respectively. In terms of safety, only 4.8%of the pa-tients showed gradesⅢandⅣneutropenia, nausea, or vomiting. Conclusion:Pemetrexed plus cisplatin is an effective and well-tolerat-ed regimen as first-line therapy for patients with lung adenocarcinoma. According to subgroup analysis, efficacy in males was signifi-cantly better than that in females. Good efficacy was observed in patients with brain metastases treated with chemotherapy and pallia-tive whole brain radiotherapy. No additional adverse effects were observed.

Clinical safety of statins / 基础医学与临床

Accumulated clinical trials have demonstrated the clinical efficacy of statins,which is closely associated with the magnitude of LDL-C reduction,in primary and secondary prevention of cardiovascular diseases.The concept of intensive LDL-C lowing has been widely accepted.Although statins are classified as a group of drugs with documented safety and tolerability,the potential risk profile in liver and skeleton muscle under the intensive treatment with large dose has drawn great attention.