Drug Of First Choice Research Articles

Diagnostic and therapeutic approach to drug-resistant juvenile myoclonic epilepsy

ABSTRACT Introduction Juvenile myoclonic epilepsy (JME), also known as Janz syndrome, is a common form of generalized epilepsy of presumed genetic origin representing up to 10% of all epilepsy cases. Despite adequate anti-seizure medication (ASM) treatment, seizures persist in one-third of JME patients. Areas covered A literature search was conducted using Pubmed search on the topics of drug-resistant JME. Expert Opinion About 30% of JME patients are drug-resistant. Valproate (VPA) is considered the first-choice drug. In women of childbearing potential, levetiracetam (LEV) should represent the first-choice treatment. Alternative monotherapy or add-on therapy should be considered in subjects with resistant seizures after the exclusion of pseudo-drug resistance. The choice of the add-on ASM depends on the predominant seizure type. In subjects with persistent bilateral tonic-clonic seizures, LEV or lamotrigine should be firstly considered. In patients with difficult-to-treat myoclonic seizures, clonazepam or LEV are recommended. In case of persistent absences, ethosuximide should be considered. With appropriate selection and safeguards in place, VPA should remain available as an option in women of childbearing potential whose seizures are resistant to other treatments.

In silico interactions of statins with cell death-inducing DNA fragmentation factor-like effector A (CIDEA)

Statins are the low-density lipoproteins (LDL)-cholesterol-lowering drugs of first choice and are used to prevent the increased risk of cardiovascular and cerebrovascular diseases. Although some of their effects are well known, little is known about their ability to regulate other lipid-related proteins which control apoptotic mechanisms. The aim of this study was to explore whether statins can bind to cell death-inducing DNA fragmentation factor-like effector A (CIDEA), which might be a possible pleiotropic mechanism of action of these drugs on the modulation of apoptosis and lipid metabolism. The structures of statins were subjected to molecular docking and dynamics with the human CIDEA protein to investigate the interaction pattern and identify which residues are important. The docking results indicated that atorvastatin and rosuvastatin showed the best interaction energy (−8.51 and −8.04 kcal/mol, respectively) followed by fluvastatin (−7.39), pitavastatin (−6.5), lovastatin (−6.23), pravastatin (−6.04) and simvastatin (−5.29). Atorvastatin and rosuvastatin were further subjected to molecular dynamics at 50 ns with CIDEA and the results suggested that rosuvastatin-CIDEA complex had lower root-mean square deviation and root-mean square fluctuation when compared with atorvastatin-CIDEA. Since two arginine residues -ARG19 and ARG22-were identified to be common for the interaction with CIDEA, a single-point mutation was induced in these residues to determine whether they are important for binding interaction. Mutation of these two residues seemed to affect mostly the interaction of atorvastatin with CIDEA, suggesting that they are important for the binding and therefore indicate another possible metabolic mechanism of the pleiotropic effects of this statin.

Growth Inhibitory Effects of Ester Derivatives of Menahydroquinone-4, the Reduced Form of Vitamin K2(20), on All-Trans Retinoic Acid-Resistant HL60 Cell Line

The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K2(20)), used for osteoporosis treatment, does not have serious adverse effects. It has been reported that MK-4 has growth-inhibitory effects on HL60 cells by inducing apoptosis via the activation of Bcl-2 antagonist killer 1 (BAK). However, the effect of MK-4 on ATRA-resistant APL has not been reported. Here, we show that ester derivatives of menahydroquinone-4 (MKH; a reduced form of MK-4), MKH 1,4-bis-N,N-dimethylglycinate (MKH-DMG) and MKH 1,4-bis-hemi-succinate (MKH-SUC), exerted strong growth-inhibitory effects even on ATRA-resistant HL60 (HL-60R) cells compared with ATRA and MK-4. MKH delivery after MKH-SUC treatment was higher than that after MK-4 treatment, and the results indicated apoptosis induced by BAK activation. In contrast, for MKH-DMG, reconversion to MKH was slow and apoptosis was not observed. We suggest that the ester forms, including monoesters of MKH-DMG, exhibit another mechanism independent of apoptosis. In conclusion, the MKH derivatives (MKH-SUC and MKH-DMG) inhibited not only HL60 cells but also HL-60R cells, indicating a potential to overcome ATRA resistance.

Effects on monotherapy and reduction of antipsychotic drugs by clozapine therapy in Japanese patients with treatment-resistant schizophrenia.

The schizophrenia guidelines in Japan and many other countries describe clozapine as the first-choice drug for patients with treatment-resistant schizophrenia. However, there have been no reports to date on the effects of the introduction of clozapine on the prescription of other antipsychotics and concomitant drugs. In this study, we retrospectively investigated the prescription of antipsychotics and concomitant drugs before vs 6months after and 12months after switching to clozapine. Clozapine was introduced to 62 patients with treatment-resistant schizophrenia, and 51 patients continued on clozapine therapy. Six months after switching to clozapine, there was a significant decrease in the mean number of antipsychotic drugs (2.04±0.75 vs 1.10±0.30: p<0.001) and in the mean chlorpromazine equivalent value (1024±73mg/day vs 781±391mg/day: p<0.001) compared to before switching. Moreover, antipsychotic monotherapy increased from 24% to 90% after switching to clozapine. In addition, the number of concomitant benzodiazepines, anti-parkinson drugs and antidepressants also significantly decreased 6 and 12months after switching to clozapine (p<0.001 for benzodiazepines and anti-parkinson drugs, and p<0.05 for antidepressants). Our study suggests that switching to clozapine may reduce the use of antipsychotic combination therapy, and may also reduce the number of concomitant drugs.

Mortalidade associada ao uso da digoxina no tratamento da fibrilação atrial: uma revisão integrativa

A fibrilação atrial (FA) é a arritmia mais prevalente, desencadeadora de um ritmo cardíaco irregular e acelerado. Embora nem sempre seja o fármaco de primeira escolha, a digoxina ainda é bastante usada, apesar de haver uma linha tênue entre seus efeitos terapêuticos, adversos e a mortalidade. Diante disso, o objetivo desse estudo é buscar evidências clínicas sobre a correlação entre o uso da digoxina e a mortalidade em pacientes com FA. Assim, foi realizada uma pesquisa bibliográfica, utilizando os descritores “(Digoxin) AND (Atrial fibrillation) AND (drug therapy)”, nas bases de dados PubMed, Biblioteca Virtual em Saúde (BVS), Scientific Eletronic Library Online (Scielo) e Cochrane. A busca foi realizada durante o mês de fevereiro de 2021. Após a aplicação dos critérios de inclusão definidos, foram selecionados 15 estudos. Após análise, evidenciou-se o número crescente de estudos que relacionam a mortalidade à terapêutica com digoxina em paciente com FA e em associação a comorbidades, como insuficiência cardíaca (IC). Logo, embora não haja um consenso, a mortalidade foi superior nos grupos de portadores de FA, com cardioversor desfibrilador ou não, que utilizaram a digoxina; sendo a mortalidade ainda maior em idosos, em portadores de doenças renais, em pacientes com FA sem IC e na ausência de monitorização terapêutica. Diante das evidências apresentadas nessa revisão, podemos afirmar que o uso de digoxina em pacientes com FA deve ser evitado ou feito com cautela e acompanhamento rigoroso.

Niepożądane odczyny po szczepieniu przeciw COVID-19 – jak postępować?

We do not have an effective medicine for COVID-19, and we only have symptomatic treatment. The best treatment is prophylaxis, which in infectious diseases is based on vaccinations. Years of using vaccinations have led to the disappearance or significant reduction of infectious diseases. Currently, in Poland, we have three vaccines against COVID-19: two mRNA (Comirnaty by Pfizer/BioNTech and Moderna COVID-19 vaccine) and vector vaccines (COVID-19 Vaccine AstraZeneca). Vaccines are highly effective in protecting against the onset of COVID-19 symptoms in large clinical trials. Vaccines can cause adverse vaccine reactions (any vaccine-related medical condition that has occurred within 4 weeks of vaccination). Studies show that adverse vaccine reactions after the COVID-19 vaccine occurs in about 0.03–0.2% of the vaccinated. The most common adverse reactions were injection site pain (&gt; 80%), fatigue (&gt; 60%), headache (&gt; 50%), myalgia (&gt; 30%), chills (&gt; 30%), arthralgia (&gt; 20%) fever (&gt; 10%), usually mild or moderate, subsiding in a few days. Adverse reactions should be treated with painkillers and antipyretics – paracetamol and ibuprofen. Both paracetamol and ibuprofen are well researched preparations, with high safety and effectiveness. The antipyretic and analgesic effect of both drugs is similar. The condition for a good effect is the use of an appropriate, recommended dosage. Now paracetamol appears to be the drug of first choice for the treatment of pain and fever following COVID-19 vaccination. However, knowledge about immunization and vaccines is growing steadily and recommendations are changing. We need to follow up-to-date information and adapt our activities to changing medical knowledge.

Effect of Food and Dosing Regimen on Safety and Efficacy of Proton Pump Inhibitors Therapy—A Literature Review

Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI dose (“PPI failure”) is often reported, especially in patients with gastroesophageal reflux disease. Poor compliance seems to be one of the main causes of PPI failure; hence, it is crucial to gain knowledge on how to properly administer PPIs. In this review, we aimed to evaluate the effect of food, beverages, and dosing regimen on pharmacokinetics and pharmacodynamics of PPIs and to frame recommendations for healthcare professionals to improve both patient’s counseling and compliance to treatment with PPIs. A total of 201 papers were identified following a literature search. After full-text evaluation, 64 studies were included in the review. Co-administration of PPIs with a meal may affect both their bioavailability and effectiveness; however, the influence of food depends on the type of drug and its formulation. Except for pantoprazole, PPIs can be administered in the morning or evening; however, morning intake generally provides better daytime control of gastric acidity. In most cases, the choice of the proper schedule of administration should be based on the patient’s symptoms and individual dosing preferences.

Development of a New Polymeric Nanocarrier Dedicated to Controlled Clozapine Delivery at the Dopamine D2-Serotonin 5-HT1A Heteromers

Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-l-glutamic acid (PGA) and poly-l-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.

Assessing the antiproliferative effect of biogenic silver chloride nanoparticles on glioblastoma cell lines by quantitative image-based analysis.

Glioblastoma is the most life‐threatening tumour of the central nervous system. Temozolomide (TMZ) is the first‐choice oral drug for the treatment of glioblastoma, although it shows low efficacy. Silver nanoparticles (AgNPs) have been shown to exhibit biocidal activity in a variety of microorganisms, including some pathogenic microorganisms. Herein, the antiproliferative effect of AgCl‐NPs on glioblastoma cell lines (GBM02 and GBM11) and on astrocytes was evaluated through automated quantitative image‐based analysis (HCA) of the cells. The cells were treated with 0.1‐5.0 μg/ml AgCl‐NPs or with 9.7‐48.5 μg/ml TMZ. Cells that received combined treatment were also analysed. At a maximum tested concentration of AgCl‐NPs, GBM02 and GBM11, the growth decreased by 93% and 40%, respectively, following 72 h of treatment. TMZ treatment decreased the proliferation of GBM02 and GBM11 cells by 58% and 34%, respectively. Combinations of AgCl‐NPs and TMZ showed intermediate antiproliferative effects; the lowest concentrations caused an inhibition similar to that obtained with TMZ, and the highest concentrations caused inhibition similar to that obtained with AgCl‐NPs alone. No significant changes in astrocyte proliferation were observed. The authors’ findings showed that HCA is a fast and reliable approach that can be used to evaluate the antiproliferative effect of the nanoparticles at the single‐cell level and that AgCl‐NPs are promising agents for glioblastoma treatment.

Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History.

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.

Pharmacoeconomic analysis of first-choice antimicrobial drugs prescribed for outpatient treatment of non-severe community-acquired pneumonia

The study aimed to perform a pharmacoeconomic analysis of antimicrobial drugs (AMDs) prescribed for the treatment of community-acquired pneumonia (CAP) in outpatient conditions. Materials and methods . 650 medical histories of patients aged 18 to 65 years old with a diagnosis of CAP who received outpatient treatment in a larg Moscow municipal polyclinic in 2018-2019 were selected for pharmacoeconomic analysis. A model of antimicrobial drug consumption was built based on actual Algorithms of Patients’ Management endorsed by the Moscow Department of Healthcare (MDH) in 2018. The analysis of the used AMPs costs in real medical practice and the simulated situation was carried out. To process the obtained results, "Statistica 13.0" software was used Results . The studied sampling of 650 medical histories included 386 (59.4%) women and 264 (40.6%) men with an average age of 39.8±16.8 years The average real clinical course cost of antimicrobial treatment calculated with a reference to the price and the percentage of total AMDs administered was worth 617.50 rubles. A comparison of the calculated average actual and simulated average AMDs course costs revealed that outpatient treatmen of CAP patients with adherence to the current MDH Algorithms would cost 394.13 rubles what would be 1.6 times more cost-effective than in the current practice. Conclusions. A course of outpatient treatment of CAP with aminopenicillins and macrolides in accordance with the actual MDH Algorithms regarding the preferences of doctors when choosing antimicrobial drugs within groups would cost on average 394.13 rubles which makes it more cost-effective as compared to real practice expenses.

Knowledge and Practice of BDS Graduates Regarding Antibiotic Prophylaxis in Infective Endocaraditis

Objective: The objective of the study was to find out the BDS graduates’ knowledge regarding antibiotic prophylaxis in infective endocarditis according to Amerian Dental Association guidelines.Methodology: A questionnaire, containing 28 questions, was distributed among BDS graduates who were serving at Khyber College of Dentistry during the period between April 2018 to June 2018.Results: In total 116 questionnaires were distributed among which 85 graduates responded back with response rate of 73.27%.Most graduates used multiple sources to gain knowledge. Most graduates (92.45%) knew that patients with previous history of endocarditis and patients suffering from rheumatic heart disease are the conditions which need antibiotic prophylaxis. In case of procedures which need antibiotic prophylaxis the highest percentage of correct answers was for periodontal surgery (98.11%) followed by extraction (92.45%). Regarding regime of antibiotics most graduate were of the option that penicillin is the first choice of drug and 1g of it should be given.Conclusion: Most of the graduates had an inadequate knowledge regarding use of antibiotic prophylaxis against infective endocarditis and were unaware of the current guidelines, so there should be trainings and workshops to refresh their knowledge regarding current practices.

Increased metformin dosage suppresses pro-inflammatory cytokine levels in systemic circulation and might contribute to its beneficial effects

ABSTRACT Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder, characterized by persistent elevation of blood glucose either due to insulin resistance or insulin insufficiency. Metformin is the recommended first choice of drug for the management of T2DM and is known to improve insulin sensitivity and prevents hyperglycemia by reducing chronic inflammation. T-helper type 1 (Th1) and type 17 (Th17) cells, are important pro-inflammatory CD4+ T cell subsets secreting TNF-α, and INF-γ (Th1), and interleukin 17 (Th17). These cytokines have been shown to play a crucial role in inflammation, insulin resistance, and the development of T2DM. Here, we explore the effect of different metformin dosages on pro-inflammatory cytokine (TNF-α, INF-γ, GM-CSF and IL-17) levels in systemic circulation among T2DM patients in Ghana, since inflammatory responses and cytokines play significant roles in the pathogenesis and progression of T2DM patients on metformin. Two hundred and nine (209) consenting T2DM patients receiving treatment at the Diabetic unit of the Komfo Anokye Teaching Hospital (KATH) in the Ashanti region of Ghana were recruited in a hospital-based cross-sectional study design. Blood samples were collected and serum obtained from each participant were analyzed for the concentrations of TNF-α, INF-γ, GM-CSF and IL-17 cytokine levels by solid-phase sandwich ELISA. We observed that participants on 3000 mg/day dose of metformin had significantly lower levels of TNF-α (p < .001) and IFN-γ (p = .014) compared to those on other dosages (1000 mg and 2000 mg/day). However, GM-CSF and IL-17 levels were not affected by increased metformin dosages. After adjusting for age, gender, dose and duration of metformin use, we observed that participants who took higher doses of metformin had significantly reduced levels of TNF-α (β = −0.0297, 95% CI = (−0.005 to −0.002) p < .001. Metformin dosage independently predicted reduced TNF-α levels with 14.4% variations in the metformin dosage levels. Increased metformin dosage suppresses TNF-α levels in systemic circulation and hence might contribute to its beneficial effects.

Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature

BackgroundIntestinal lymphangiectasia is a rare disease. Thus, prospective studies are impossible, and therapy is still controversial. Several medicines are suggested for treatment but there are no existing indications for drug choice and treatment guidelines. We aimed to introduce the action mechanism of each drug and treatment overview in a single-center experience and a review of the literature on second-line therapy for primary intestinal lymphangiectasia.MethodChildren under 18 years old diagnosed with intestinal lymphangiectasia from June 2000 to June 2020 were included and retrospectively reviewed in the study. Capsule endoscopy, MR lymphangiography, or whole-body MRI for investigating the extent of abnormal lymphatic vessels in addition to endoscopy and biopsy were conducted. The individual treatment approaches depended upon the lymphangiectasis locations involved.ResultsOnly one patient showed a response to dietary therapy. One patient was successfully cured after two therapeutic lymphatic embolization. Octreotide was tried for two patients who had extensive lymphangiectasis. Lymphangiectasis recurred when octreotide was used for 3 months in one patient, and there was no effect in the other patient. Sirolimus was tried for four patients. Two of them had abnormal lymphatic lesions only in the intestine, and the others had extensive lymphangiectasis. The former group showed clinical improvement after 3–4 months of sirolimus treatment, whereas the latter group showed clinical improvement only after 1 month of sirolimus treatment.ConclusionSurgery or embolization is a potential therapeutic option for patients with focal abnormal lymphatic lesions. Octreotide is not an optimal choice for patients with extensive lymphangiectasis. Sirolimus is an effective and safe drug and can be the first drug of choice for patients with extensive lymphangiectasis.

Depression therapy for somatic diseases

A review of works devoted to the problem of psychopharmacotherapy of depression in general medical practice is presented. The issues of its comorbidity with somatic and neurological diseases, as well as multimorbidity are discussed. Both direct and side-effects of antidepressants, which are important for effective therapy of not only affective disorders proper, but also the symptoms of the leading pathology, are considered in detail for individual organs and systems. The analysis of the preferred pharmacological classes of antidepressants, which are drugs of first choice, taking into account the somatic condition of the patient, is carried out, and drugs are indicated, the appointment of which is undesirable for the treatment of a patient with a certain disease. The presented results are aimed both at increasing the efficiency of therapy for patients with general medical level of health care, and at increasing the safety of treatment of psychiatric patients with concomitant somatic disorders.

The causes of non-adherence to methotrexate in patients with rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic progressive autoimmune inflammatory systemic disease; methotrexate is the first drug of choice to retard the disease progression. Objective: To elucidate the main factors that leading to non-adherence to methotrexate in patients with rheumatoid arthritis. Method: In this cross-sectional study, one hundred twenty-two (122) patients diagnosed with RA > 18 years old on methotrexate (mono or combined therapy) for at least three months. Data were recorded including demographic data, socioeconomic status, education level, disease duration, duration of methotrexate therapy, current weekly methotrexate dose, concomitant drugs, and factors might contribute to non-adherence. Non-adherence was considered when three or more of weekly dose of methotrexate were omitted in the last 8 weeks. Results: 38 patients (31.14%) were non-adherent. Patients with longer disease duration, those with higher education level, and on concomitant steroid had higher rate of non-adherence. Among the factors contributing to non-adherence are: Methotrexate Don't treat arthritis symptoms well 25 patients (65.78%), social myths 24 patients (63.15%), Don't need it when feeling well: 22 patients (57.89%) were on the top of list. Conclusion: The patients with non-adherence in the current study constitute about one third of the patients. Good adherence rate can increase by good doctor-patients communication and continuous patients’ education and counseling by treating rheumatologist.

Morphological and Morphometrical Analyses of Fracture-Healing Sites of an Atypical Femoral Fracture in Patients with and without Long-Term Bisphosphonate Treatment for Osteoporosis: A Report of Two Cases

Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.

5 giorni di antibiotico per le polmoniti non complicate sono sufficienti: i risultati di non inferiorità del SAFER RCT

5 days of antibiotic for uncomplicated pneumonia is enough: the non-inferiority results of the SAFER RCT The most important guidelines for the treatment of community-acquired pneumonia (CAP) indicate amoxicillin as the drug of first choice, however there is a lack of evidence-based indications about the duration of this therapy. This study conducted in 2 emergency departments in Canada randomized 281 children aged 6 months to 10 years with CAP without the need for hospitalization to treatment with high-dose amoxicillin for 5 days versus a traditional 10 day therapy. In terms of clinical recovery, both groups presented comparable results. In fact, the “per protocol” analysis, recommended for a “non-inferiority” design, did not formally provide this result. The exclusively clinical recruitment criteria (any investigations were optional), well reflect the reality of primary care, and the results, albeit with some limitations, suggest that in uncomplicated CAP, brief therapy should be considered in the guidelines.

Bol u grudima i prehospitalno kašnjenje

Aim was to show the duration of chest pain in patients with Angina pectoris (AP) and acute coronary syndrome (ACS) prior to reporting to the ambulance as well as the patients' self management of the pain. Materials and methods. The study was done between 1st August 2014th and 1st October 2018th in the infirmary of EMS in Belgrade. The study involved 161 patients, out of 9437 patients in total, who were treated by one doctor and with confirmed or suspected diagnosis of an ACS or AP. Results. Patients with AP most commonly waited between 2-24 hours, while the patients with ACS waited &lt;1h from the pain onset until contacting EMS. Most patients with MI (17) as well as with AP (79) did not take any kind of therapy, while some patients administered one or more drugs in order to relieve the pain. In patients with AP, the drugs of choice were antihypertensive medications (17.42%) and in MI patients Nitroglycerin and analgesics (31.03%). All patients previously diagnosed with MI and AP have self-administered Nitroglycerin in 12.42% of cases. Conclusion. Patients with AP wait longer when having chest pain before calling EMS from patients with ACS, but their self-administered drugs of choice were antihypertensive medications. Nitroglycerine as the first appropriate drug of choice is used less and in most cases patients even do not have it readily available.

Resistance to Fluoroquinolones and Other Antimicrobials in Culture-Positive &amp;lt;i&amp;gt;Salmonella typhi&amp;lt;/i&amp;gt; Isolates in Gulbarga, South India

Background: Typhoid fever is a major public health concern in developing countries. The upsurge in the occurrence of bacterial isolates that are resistant to nalidixic acid; with reduced susceptibility to ciprofloxacin in typhoidal Salmonellae constitutes a challenge to the clinician. Methods: In order to better understand the epidemiology of Salmonella infections in South India, Salmonella typhi isolates were screened from various healthcare centers. Salmonella isolates were identified by using standard phenotypic, serological, antibiotic susceptibility and molecular methods. Results: Among a total of 100 S. typhi isolates 9% were found to be multidrug resistant and 30% were nalidixic acid resistant. Isolates with reduced susceptibility to ciprofloxacin displays single base mutations in the gyrA gene. A very low rate of 1% resistance was found to ciprofloxacin. The only one isolate with ciprofloxacin MIC ≥ 4 μg/ml also showed single mutation in the QRDR of the gyrA gene in S. typhi (GenBank accession no. HQ176349-HQ176368). Conclusions: A very low rate of nalidixic acid resistance with reduced susceptibility to ciprofloxacin was observed in comparison to other endemic areas in isolates of S. typhi from Gulbarga, South India, with steadily increasing NAR S. typhi but decreasing MDR isolations over the study period. This is most likely due to an increased use of ciprofloxacin as a first line drug of choice over more traditional antimicrobial agents for the treatment of typhoid fever.