Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety of selective serotonin reuptake inhibitor treatment in recovering stroke patients

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are widely used for psychiatric complications after stroke. Studies have indicated additional effects, and SSRIs could potentially be used as enhancers of stroke recovery. However, beneficial effects should be weighed against potential adverse effects. In particular, the possible association with cerebrovascular events has raised concern. Areas covered: We review the literature on cerebrovascular events associated with SSRI treatment after stroke. The possible beneficial effects of SSRI treatment for stroke recovery and survival, and potential safety concerns, are discussed. Expert opinion: Evidence suggests that SSRIs may enhance stroke recovery. Most studies on cerebrovascular risk are from non-stroke populations and little is known about recurrent events and mortality post-stroke. In non-stroke populations treatment has been associated with increased risk of intracerebral and intracranial hemorrhage; however the absolute risk is low. The association between SSRIs and ischemic stroke is less clear. Randomized stroke trials indicate that treatment is safe and well tolerated, and the most common side effects are often benign and transient. The trials are small however and not powered to detect potential differences in cerebrovascular events. We await several ongoing large randomized trials before SSRIs can be recommended as a routine pharmacotherapy in stroke recovery.
Fluoride intake of young male adults in the United States

The total daily fluoride intake for young male adults living in four geographical areas of the United States has been estlinated by the analysis of "market basket collections" obtained in 1975 and 1977. The fluoride intake in 1975 varied from 0.912 mg/day in an unfluoridated city (Kansas City, Mo.) to 1.720 mg/day in a fluoridated city (Atlanta, Ga.). The 1977 collection from San Francisco, Calif. contained more fluoride (1.636 mg/day) than the 1975 collection (1.213 mg/day). The level of intake found in this study is less than that reported by San Filippo and Battistone (Chin. Chem. Acta 31: 453, 1971) who analyzed similar collections from Baltimore, Md. in 1967 to 1968 (2.09 to 2.34 mg/day). This study, as well as the earlier one, indicates that relatively low levels of fluoride are being consumed in the United States by the young adult male 16 to 19 years of age. Am. J. Clin. Nuir. 33: 328-332, 1980.
Obesity and polycystic ovary syndrome: association with androgens, leptin and its genotypes

Obesity and hyperandrogenaemia are key features of polycystic ovary syndrome (PCOS). The aim of this study was to investigate whether leptin and androgens are associated with obesity in PCOS subjects and identify whether there exist any genetic alterations in leptin gene in women with PCOS. The results reveal that leptin levels are elevated in women with PCOS and associate with BMI. However, irrespective of the obesity status leptin levels are higher in PCOS cases indicating that increased BMI/obesity may not be the only factor contributing to elevated levels of leptin. With regard to testosterone and androstenedione, the levels were increased in obese individuals irrespective of PCOS status. No correlation between leptin and androstenedione or testosterone was observed in controls and PCOS subjects. The single-nucleotide polymorphism G19A detected in the untranslated exon 1 of leptin gene was not associated with PCOS and does not contribute to elevated levels of leptin. The results overall suggest that androgen and leptin levels are increased in PCOS and obesity. It demonstrates that obesity is a confounding factor for hyperandrogenaemia irrespective of their PCOS status. The study rules out role of obesity status and leptin genotype in increase in leptin levels observed in PCOS cases.
Drug safety evaluation of lenvatinib for thyroid cancer

Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR1,2,3,4, FGFR1,2,3,4, PDGFR-α as well as RET and KIT signaling network. Its activity against radioiodine-resistant differentiated thyroid cancer (DTC) has been recently demonstrated. Patients, who were given lenvatinib, showed significantly longer median progression free survival than placebo group, 18.3 vs 3.6 months, respectively. This review is focused on lenvatinib safety profile in patients treated due to DTC and medullary thyroid carcinoma. Among the most frequent lenvatinib-related adverse events (AEs) were hypertension, proteinuria, diarrhea, appetite decrease, weight loss, nausea and stomatitis. Although a lot of them were manageable, in 35–68% of patients dose reduction was required. Nevertheless, only 15% of subjects withdrew the drug due to its toxicity.Areas covered: published results of clinical trials phase II and III investigating both safety and efficacy of lenvatinib in thyroid cancer.Expert opinion: Lenvatinib shows acceptable safety profile in patients with thyroid carcinoma. Treatment-related side effects are usually manageable by dose modifications or by concomitant non-pharmacological and pharmacological treatment. However, the early recognition of any potential drug toxicity is crucial to avoid serious complications as well as to keep a patient on drug as long as the treatment is beneficial.
Evaluation of dolutegravir safety for the treatment of HIV-1

Introduction: Dolutegravir (DGV) is the newest integrase inhibitor approved for the treatment of HIV-1 infection in both treatment-naive and experienced adults and adolescents. This article reviews the safety of DGV for the treatment of HIV-1 infection. Areas covered: The PubMed database was searched using the keywords ‘DGV’ and ‘HIV’. In addition, conference proceedings from Conference on Retroviruses and Opportunistic Infections, International AIDS Society and European AIDS Clinical Society meetings were searched for presentations on DGV clinical studies. Expert opinion: DGV has demonstrated a favorable safety profile and is well tolerated for the treatment of HIV-1 infection. Unlike raltegravir, DGV can be given once daily, and unlike elvitegravir, it does not require pharmacologic boosting to achieve consistent blood levels.
Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation

Introduction: Oral anticoagulation is the mainstay for stroke and thromboembolic event prevention in patients with atrial fibrillation (AF). Given limitations of warfarin therapy, non-vitamin K oral anticoagulants have been developed including direct thrombin inhibitors (i.e., dabigatran etexilate). Dabigatran etexilate has been tested thoroughly in terms of efficacy and safety in clinical trials and studies, involving ‘real-world’ cohorts. In this review, currently available evidence in patients with non-valvular AF is discussed. Areas covered: The pharmacology, efficacy and safety, and current aspects of use of dabigatran etexilate in patients with non-valvular AF are reviewed in a comparative manner to warfarin both for chronic anticoagulation and in different clinical settings. Expert opinion: Dabigatran etexilate appeared to have several pharmacokinetic and pharmacodynamic advantages over warfarin, as well as a favorable efficacy and safety profile being at least noninferior and often superior to warfarin in patients with non-valvular AF. The latter was shown in the clinical trials, meta-analyses and studies with ‘real-world’ data. Currently ongoing trials will expand the body of evidence on warfarin and will aid decision making in currently controversial areas. Important limitations of dabigatran etexilate include contraindications for its use in patients with prosthetic heart valves and end-stage chronic kidney disease.
Surgical embolectomy for middle cerebral artery occlusion after thrombolytic therapy: A report of two cases

Background: Occlusion of the intracranial main trunk results in a poor functional outcome and a high mortality rate. Accordingly, some revascularization procedures such as intravenous administration of recombinant tissue plasminogen activator (rt-PA), endovascular surgery, or surgical embolectomy in the very acute stage have been attempted. Case Description: We describe two patients with middle cerebral artery occlusion due to cardiogenic embolism. One patient was subjected to surgical embolectomy shortly after intravenous rt-PA and the other was subjected to same after intra-arterial urokinase. Complete recanalization without new cerebral infarction territory was achieved in both patients. Conclusion: Based on our experience, we think that surgical embolectomy is an effective and safe procedure and should be attempted when no response to early thrombolytic therapy is obtained.
Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention

ABSTRACT Introduction: Tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis is a novel HIV prevention strategy for individuals at increased sexual risk for HIV infection. For any biomedical prevention intervention, the bar for tolerating adverse effects in healthy persons is high compared to therapeutic interventions. Areas covered: We provide a concise summary of the clinical safety of TDF-based pre-exposure prophylaxis with focus on TDF-related effects on tolerability, kidney function, bone density, HIV resistance, sexual and reproductive health. The evidence base for this review is derived from a literature search of both randomized and observational studies evaluating efficacy and safety of TDF-based PrEP, TDF alone or in combination with emtricitabine, identified from PUBMED and EMBASE electronic databases, clinicaltrials.gov and major HIV conferences. Expert opinion: TDF-based pre-exposure prophylaxis is a potent intervention against HIV acquisition when taken which is generally safe and well tolerated. The risk of the small, non-progressive, and reversible decline in glomerular filtration rate and bone mineral density as well as the potential selection for drug resistance associated with PrEP are outweighed, at the population level and broadly for individuals, by PrEP’s substantial reduction in the risk of HIV infection.
A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor

ABSTRACT Introduction: For the last 15 years, imatinib mesylate has been the first line treatment of choice for advanced (metastatic) GIST. Areas covered: This review describes key efficacy data on imatinib for the treatment of GIST, and focuses on safety and tolerability of imatinib, with emphasis on common adverse events management and long term toxicity profile. Expert opinion: Imatinib has been the standard of care for metastatic GIST and probably will continue to be so for the next few years. Still, despite dramatic responses initially, imatinib drug resistance continues to be the major factor for treatment discontinuation. The toxicity profile of imatinib has been well characterized, and although the majority of patients experience an adverse event during treatment with imatinib, these side effects are usually mild and manageable, with the majority of patients continuing treatment uninterruptedly. Early concerns regarding imatinib related cardiotoxicity in GIST have not been confirmed in large prospective randomized trials, with reports indicating a low incidence of approximately 0.2%-0.4%. Future strategies for treatment of imatinib resistant GIST will probably include novel tyrosine kinase inhibitors, combination therapies or immunotherapy.
The safety of treatment options for elderly people with acute myeloid leukemia

ABSTRACT Introduction: Life expectancy in elderly patients with acute myeloid leukemia (AML) is a function of age, disability, and co-morbidity, combined with leukemia characteristics. There is currently no consensus regarding the optimal therapeutic strategy for older adults with AML. Although selected older adults with AML can benefit from intensive therapies, recent evidence supports the use of lower-intensity therapies in most patients and emphasizes the importance of tolerability and quality of life. Areas covered: Results of the current clinical trials and safety data are reviewed. Expert opinion: Treatment recommendations for elderly patients with AML need to be individualized. In order to avoid toxicities, hematologists should collaborate more with geriatricians to identify clues of vulnerability in elderly patients through the study of functional physical, physiological, cognitive, social, and psychological parameters.
A review of antidepressant-induced urinary hesitancy: a focus on levomilnacipran ER including two case presentations(5633)

ABSTRACT Introduction: Levomilnacipran ER was recently FDA approved as Fetzima® for the treatment of MDD. Urinary hesitancy can be an adverse event associated with levomilnacipran treatment. Areas covered: This manuscript details the longitudinal course of levomilnacipran-induced urinary hesitancy in 2 cases that were in a pivotal clinical trial, examining possible predisposing factors and treatment issues. This manuscript also reviews the literature comparing urinary hesitancy associated with levomilnacipran versus other antidepressants. Antidepressants that are potent norepinephrine reuptake inhibitors like levomilnacipran, may have increased rates of associated urinary hesitancy. The latter can cause significant discomfort and a compromised quality of life. Occasionally, it can progress to urinary retention necessitating an emergency medical intervention. Expert opinion: All patients being treated with antidepressants should be carefully monitored for this side effect. Discontinuation of treatment or reduction of the dose of antidepressant frequently relieves urinary hesitancy; alternatively, treatment with an alpha1A antagonist, e.g., tamsulosin may relieve antidepressant-induced urinary hesitancy within hours to days; such strategies allow for continued antidepressant treatment without urinary hesitancy recurring. Thus, with appropriate clinical care, the benefits using levomilnacipran outweigh its risks.
Assessment of clinical risk factors for drug-resistant epilepsy in children and teenagers

Introduction: Epilepsy is one of the most common neurological illnesses occurring in children. In approximately 20–30% of cases it is drug-resistant. Aim of the research: To assess the already-known risk factors, analyse the rarely described ones, and find new causes of epilepsy drug resistance in children, taking into account the level of impact of each factor. Material and methods: The study comprised 152 of all 383 children hospitalised in 2012 at the Neurology Department of the Polish Mother’s Memorial Hospital in Lodz due to epilepsy. Based on medical documentation, neurological examination, and our own questionnaire, we divided patients into two groups: drug-resistant epilepsy or drug-sensitive epilepsy. We compared the type, level of influence, and prevalence of different factors. For statistical analysis, the χ2 test was used. Statistical significance was set at p < 0.05. Results: Drug-resistant epilepsy was found in 64 patients (42.1%), and drug-sensitive epilepsy was found in 88 patients (57.9%). Factors that were most probable to cause drug resistance included: high prevalence of seizures (Cramer’s V = 0.66), type of epileptic syndrome (V = 0.62), psychomotor developmental delay (V = 0.62), and occurrence of status epilepticus (V = 0.6). Factors such as infections of CNS in early childhood, repeated severe infections of airways in childhood, and mother’s infectious diseases with high fever during pregnancy were rare or non occurring (Cramer’s V = 0.41, 0.32, and 0.31, respectively). Conclusions: The study confirmed the previously known causes of drug resistance and indicated the significance of under estimated inflammatory and infectious factors involving pyrexia, in children and also in mothers during pregnancy.
Some reflections on frailty in elderly patients with cancer

The recognition that the elderly with cancer are frequently neglected has led to an upsurge in calls to address their needs. This paper argues that there needs to be caution before launching wholesale into a new sub-speciality, that of ‘geriatric oncology’, when we have yet to delineate the characteristics of cancer in the elderly. The most important factor in determining the best treatment approach for any individual with cancer is to be able to distinguish accurately chronological age from physical vulnerability or frailty. Current methods for determining vulnerability in patients with cancer are criticized; what is needed is the development of indices of frailty so that treatment and care packages for the elderly can be tailored to those who are ‘frail’, whilst treating the ‘non-frail’ as any other adult with cancer.
Faculty development in the new millennium: key challenges and future directions

Faculty development initiatives in the year 2000 will need to respond to changes in medical education and health care delivery, to build on the achievements and accomplishments of the past, and to continue to adapt to the evolving roles of faculty members. To remain at the forefront, faculty development programs will need to broaden their focus, consider diverse training methods and formats, conduct more rigorous program evaluations, and foster new partnerships and collaborations. Academic vitality is dependent upon faculty members' interest and expertise; faculty development has a critical role to play in promoting academic excellence and innovation.
Sero-prevalence of Hepatitis B Surface Antigen (HBsAg) amongst Pregnant Women Attending Antenatal Clinic at the Federal Medical Centre Umuahia, Abia State, Nigeria

Despite the existence of a safe and effective vaccine, Nigeria has remained a hyper-endemic area for hepatitis B virus infection, with estimated 12% of the total population being chronic carriers. Neonates who contact hepatitis B virus infection will have an almost 90% risk of developing chronic hepatitis B surface antigen (HBsAg) carrier state and chronic liver disease. The objectives of this study were to determine the sero-prevalence of hepatitis B surface antigen among pregnant women and identifying potential risk factors associated with the infection. This study involved a total of 350 pregnant women who attended antenatal at the Federal medical Centre, Umuahia, Abia State, Nigeria. Blood samples from all consenting pregnant women were collected. A structured pro forma designed for this purpose was used to obtain socio-demographic information and the presence of risk factors. Data collated was analyzed using GraphPad Prism statistical software with P<0.05 at 95% confidence interval. The results showed that HBsAg sero-prevalence rate of 7.1% was observed in all the pregnant women tested. Sero-prevalence of HBsAg amongst parturients were more in patients within their first trimesters (11.1%), Primigravida pregnant women (8.0%), women with history of dental or surgical procedures (34.0%) and multiple sexual partners (25.0%) and in women with no formal education (37.5%). An intermediate prevalence of HBsAg was identified which justifies the need for routine screening in pregnancy in order to identify and treat the infection, thus reducing the risk of transmission of the virus. Contraceptive options aimed at prevention of pregnancy and sexually transmitted infection (STI) should be encouraged.
The vascular endothelial growth factor (VEGF) polymorphisms and the risk of endometriosis in northern Iran

Vascular endothelial growth factor (VEGF) is known to be a key molecule in the pathogenesis of endometriosis. In this study, we evaluated whether two polymorphisms −460T>C and +405G>C in VEGF are related with the susceptibility to endometriosis in northern Iran. Genomic DNA derived from patients with endometriosis and healthy women were analysed by polymerase chain reaction-restriction fragment length polymorphism. The total number of 1080 subjects (480 patients with endometriosis and 600 normal controls) was enrolled into the study. We used the Chi-square (χ2) test to evaluate each allele and genotype frequency of −460T>C and +405G>C polymorphisms among the cases and controls. The associations between the polymorphisms and the risk of endometriosis were estimated by odds ratio and their 95% confidence intervals. There was no significant differences in the VEGF −460T>C genotypes and allele frequencies between control women and endometriosis patients (P = 0.63). In contrast, an increased frequency of the +405CC genotype was observed in the patients with endometriosis as compared with the controls. The +405C allele was associated with the presence of endometriosis. It is concluded that the +405G>C polymorphism in VEGF may be associated with higher risk of endometriosis in northern Iran.
Recent advances in intravenous delivery of poorly water-soluble compounds

In recent years, with the widespread application of high-throughput screening technologies in drug discovery, an increasing number of new chemical entities with extremely poor aqueous solubility have been generated. Their poor solubility represents a major challenge for formulation of these compounds for both oral and parenteral administration. Formulations for intravenous (i.v.) application are of significant importance because they are frequently used in several key therapeutic areas, such as oncology and anesthesia. Furthermore, i.v. formulations of new compounds are often needed to determine basic biopharmaceutical parameters and to obtain proof of concept results in the early phase of product development. This review provides an overview of the recent advances in formulation approaches and drug delivery technologies for poorly water-soluble compounds applicable to i.v. administration. The advantages and disadvantages of different strategies are highlighted and an expert opinion on each technical field is presented.
The importance of ERα and ERβ gene polymorphisms in PCOS

Estrogens act through binding to estrogen receptor α (ERα) and β (ERβ). Studies in knockout mice have shown that the absence of ERα leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERβ gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERα and ERβ gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERα, as well as, the AluI and RsaI polymorphisms of ERβ were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERα polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERα as a genetic modifier of the PCOS phenotype.