Specific Drug Therapy Research Articles

Mechanisms of non-type 2 asthma.

Non-type 2 inflammation (Non-T2)-mediated asthma is difficult to define due to lack of signature biomarkers. It exists in the absence of T2-high or eosinophilic inflammation and includes neutrophilic and paucigranulocytic subtypes. Several cell types and cytokines, including Th1, Th17, IL-6, and IL-17, contribute to mechanisms of non-T2 asthma. Neutrophil extracellular traps (NETs) and inflammasome activation likely play a role in severe neutrophilic asthma. Several mechanisms lead to uncoupling of airway hyperresponsiveness and remodeling from airway inflammation in paucigranulocytic asthma. Recent research on transcriptomics and proteomics in non-T2 asthma is discussed in this review. Investigations of specific drug therapies for non-T2 asthma have been disappointing, and remain an important area for future clinical studies.

COVID-19: A review of the proposed pharmacological treatments

The emerging pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge for healthcare systems globally. The clinical course of COVID-19 and its ability to rapidly create widespread infection has major implications, warranting vigorous infection prevention and control measures. As the confirmed number of cases has surpassed 5.6 million worldwide and continues to grow, the potential severity of the disease and its deadly complications requires urgent development of novel therapeutic agents to both prevent and treat COVID-19. Although vaccines and specific drug therapies have yet to be discovered, ongoing research and clinical trials are being conducted to investigate the efficacy of repurposed drugs for treating COVID-19. In the present review, the drug candidates that have been suggested to treat COVID-19 will be discussed. These include anti-viral agents (remdesivir, ribavirin, lopinavir-ritonavir, favipiravir, chloroquine, hydroxychloroquine, oseltamivir, umifenovir), immunomodulatory agents (tocilizumab, interferons, plasma transfusions), and adjunctive agents (azithromycin, corticosteroids), among other miscellaneous agents. The mechanisms of action and further pharmacological properties will be explored, with a particular focus on the evidence-based safety and efficacy of each agent.

Recent advances in the treatment of osteoarthritis.

Osteoarthritis (OA) is one of the most debilitating diseases and is associated with a high personal and socioeconomic burden. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Efforts to identify more tailored treatment options led to the development of strategies that enabled the classification of patient subgroups from the pool of heterogeneous phenotypes that display distinct common characteristics. To this end, the classification differentiates the structural endotypes into cartilage and bone subtypes, which are predominantly driven by structure-related degenerative events. In addition, further classifications have highlighted individuals with an increased inflammatory contribution (inflammatory phenotype) and pain-driven phenotypes as well as senescence and metabolic syndrome phenotypes. Most probably, it will not be possible to classify individuals by a single definite subtype, but it might help to identify groups of patients with a predominant pathology that would more likely benefit from a specific drug or cell-based therapy. Current clinical trials addressed mainly regeneration/repair of cartilage and bone defects or targeted pro-inflammatory mediators by intra-articular injections of drugs and antibodies. Pain was treated mostly by antagonizing nerve growth factor (NGF) activity and its receptor tropomyosin-related kinase A (TrkA). Therapies targeting metabolic disorders such as diabetes mellitus and senescence/aging-related pathologies are not specifically addressing OA. However, none of these therapies has been proven to modify disease progression significantly or successfully prevent final joint replacement in the advanced disease stage. Within this review, we discuss the recent advances in phenotype-specific treatment options and evaluate their applicability for use in personalized OA therapy.

Application of Delphi method and analytic hierarchy process to establish indicator system for evaluation of rational drug use in children with primary nephrotic syndrome: Observational study.

Nephrotic syndrome (NS) can be divided into primary, secondary, and congenital NS 3 types, and primary nephrotic syndrome (PNS) accounts for about 90% of the total number of NS in children, which is a common childhood glomerular disease one. The treatment of children with PNS has been controversial and confused because of hormone tolerance, complications, multiple drug combinations, and other issues, but there are no indicators to assess the rational drug use (RDU) of children with PNS. This study aims to develop a set of indicators to assess the RDU in children with PNS.The study is an observational study and the procedure includes 3 steps:1.Systematic review: searched the websites, guidelines, and studies to establish the initial indicators.2.Expert consultation: applied the modified Delphi method among experts in the field of nephrology for a two-round collaborative consensus project. Obtained the final indicators by modifying each round based on the comments provided by the experts.3.Analytic Hierarchy Process: applied the AHP to determine the weight of each indicator.A consensus was reached after 2 rounds of the Delphi survey and each indicator was weighted. The final indicators included 2 first-rank indicators and 16 second-rank indicators. In round 1, modified 3 indicators, increase 2 indicators and delete 6 indicators. In round 2, reached consensus. The first-rank indicators comprised drug choice (46.96%) and drug usage and dosage (53.04%); The second-rank indicators aimed to the specific drug therapy, including the RDU of hormones, immunomodulators, and adjuvant drug. The score of each indicator met the requirements, therefore, childrens PNS RDU evaluation index system had been established and the index was scientific and credible.The first set indicators had been established to assess RDU of children with PNS. Monitoring these indicators will guide people towards the promotion of RDU for PNS. Whats more, the indicator provided a methodological reference for the development of other indicator sets.

COVID-19 Pandemic: Prevention and Protection Measures to Be Adopted at the Workplace

SARS-CoV-2, identified in Wuhan, China, for the first time in December 2019, is a new viral strain, which has not been previously identified in humans; it can be transmitted both by air and via direct and indirect contact; however, the most frequent way it spreads is via droplets. Like the other viruses belonging to the same family of coronaviruses, it can cause from mild flu-like symptoms, such as cold, sore throat, cough and fever, to more severe ones such as pneumonia and breathing difficulties, and it can even lead to death. Since no effective specific drug therapy has been found yet, nor any vaccine capable of limiting the spread of this pathogen, it is important for ways of preventing the spread of this infection to be established. The purpose of our research was to provide a protocol to prevent the spread of SARS-CoV-2 infection in light of the limited information related to this coronavirus. In detail, we analysed and searched targeted evidence-based guidelines issued in the various countries affected by this epidemic up till now. In addition, we analyzed the recommendations for the prevention and control of other epidemics caused by other pathogens belonging to the same family of coronaviruses or others that present the same mechanisms of transmission. General organizational measures regarding the containment and management of the epidemiological emergency of COVID-19 have been imposed by the competent authorities for an adequate and proportionate management of the evolution of the epidemiological situation. The prevention and protection organizational measures therefore aim to minimize the probability of being exposed to SARS-CoV-2. For this purpose, measures must also be taken at work to avoid new infections or even the spread of the virus where it has already been present. Furthermore, environmental measures are aimed at reducing the risk of transmission of SARS-CoV-2 to individuals through contact with infected subjects, objects, equipment, or contaminated environmental surfaces. Protective devices must be used whenever there is potentially close contact with a suspect case, especially when the potentially infected person does not wear a surgical mask that could reduce the spread of viruses in the environment. By adopting this specific prevention and protection measures recommended in the workplace, it will be possible to help overcome this COVID-19 pandemic.

Diagnosis and Treatment of VOD/SOS After Allogeneic Hematopoietic Stem Cell Transplantation.

Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) is a rare complication characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, hematopoietic stem cell transplantation (HSCT) and, less commonly, other conditions. We review pathogenesis, clinical appearance and diagnostic criteria, risk factors, prophylaxis, and treatment of the VOD occurring post-HSCT. The injury of the sinusoidal endothelial cells with loss of wall integrity and sinusoidal obstruction is the basis of development of postsinusoidal portal hypertension responsible for clinical syndrome. Risk factors associated with the onset of VOD and diagnostic tools have been recently updated both in the pediatric and adult settings and here are reported. Treatment includes supportive care, intensive management, and specific drug therapy with defibrotide. Because of its severity, particularly in VOD with associated multiorgan disease, prophylaxis approaches are under investigation. During the last years, decreased mortality associated to VOD/SOS has been reported being it attributable to a better intensive and multidisciplinary approach.

What is a reasonable rate for specific osteoporosis drug therapy in older fragility fracture patients?

Osteoporosis is the most common condition contributing to 95% of fractures in older patients hospitalized for fracture treatment. Despite the significant impact of fragility fractures on patient morbidity and mortality, efforts in optimizing osteoporotic treatment and prevention remain inadequate. In contrast, in patients with limited life expectancy, withholding specific osteoporosis drug treatment appears reasonable. The threshold between under- and overtreatment is still unclear. In 2016, we implemented a fracture liaison service (FLS) for 18months to improve the quality of osteoporosis care. We collected prospectively the patient's history, current treatment for osteoporosis, and risk factors for fragility fractures using a standardized protocol. Recommendations for drug therapy are discussed during the interdisciplinary ward round. The primary outcome parameter was a recommendation for specific osteoporosis drug treatment. We included 681 patients (mean age 82.5years, 502 (73.7%) females). The inclusion criteria were the following: age of 70years or older, admission to geriatric fracture center between April 2016 and December 2018. Based on our data, specific osteoporosis drug therapy was recommended in 467 (68.6%) patients. Six hundred fifty-one (95.6%) patients received vitamin D3, and 546 (80.2%) calcium. After adjustment, only age (every 5years, OR 0.57; 95% CI 0.45-0.72; p < 0.0001), cognitive impairment (OR 0.41; 95% CI 0.23-0.74; p = 0.003), pre-fracture mobility (OR 1.54; 95% CI 1.34-1.75; p < 0.0001), and living in a nursing home (OR 0.52; 95% CI 0.27-0.99; p = 0.049) remained as independent predictors for an indication of specific osteoporosis drug therapy. We found a higher rate of recommendations for specific osteoporosis drug therapy compared with usual treatment rates in literature. Though in some cases withholding of specific osteoporosis drug therapy seems reasonable, the main proportion of fragility fracture patients is undertreated. Our results could be a benchmark for the quality of osteoporosis care in older fragility fracture patients treated in a geriatric fracture center.

Therapeutic difficulties in vegetative epileptic seizures as a sign of acute viral encephalitis: case presentation

Acute encephalitis is a severe pathology represented by the inflammation of the brain parenchyma associated with neurological dysfunction. The etiology is predominantly viral or autoimmune, with different therapeutic approach. The typical manifestations include fever, epileptic seizures and neurological focal signs. The treatment consists in specific drug therapies regarding the etiology and rehabilitation therapies in case of incomplete recovery. We present a case of a 43-year-old woman with occipital cephalalgia and dizziness, associated with vesperal high blood pressure levels at the same hour daily. The brain MRI described possible acute encephalitis, with FLAIR and T2 hypersignal area on right parietal region and diffusion restriction. The lumbar puncture revealed no modifications and the EEG recordings showed irritative patterns. The acyclovir intravenous treatment and an antiepileptic drug were initiated. The repeated MRI revealed laminar necrosis which explained the vegetative epileptic seizures manifested with high blood pressure. The clinical status of the patient majorly improved due to specific treatment including rehabilitation interventions. Key words: acute viral encephalitis, vegetative epileptic seizures, laminar necrosis, cephalalgia, rehabilitation,

Balloon Pulmonary Angioplasty as a Treatment in Chronic Thromboembolic Pulmonary Hypertension: Past, Present, and Future.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a major cause of precapillary pulmonary hypertension leading to right heart failure and death if left untreated. In addition to pulmonary endarterectomy, which is considered the standard of care, and specific drug therapy that is not however expected to offer relief from the mechanical component of the disease, the therapeutic options for CTEPH have expanded with the development of balloon pulmonary angioplasty (BPA). The purpose of this review is a better understanding and evaluation of BPA as a treatment option in CTEPH patients. With the evolution of BPA almost all over the world, more centers outside Japan, which remains the leader for the technique, presented their results confirming the efficacy, safety, and feasibility of this procedure as a complementary strategy in the treatment algorithm of CTEPH. Summarizing, more data from all over the world confirm that BPA is a challenging but potentially effective intervention for the treatment of inoperable CTEPH patients. However, there is a need for standardization of the technique, and furthermore, large, international, multicenter randomized controlled trials comparing BPA with the other treatment modalities of CTEPH are imperative.

The Pulmonary Arterial Hypertension Associated With Ventricular Septal Defects: A Single-Centre Experience In The Republic Of Kazakhstan.

The aim of this study was to evaluate the impact of pulmonary arterial hypertension on outcomes following surgical or transcatheter repair of isolated ventricular septal defect in the Republic of Kazakhstan.&nbsp;Echocardiography and catheterisation reports of children with isolated ventricular septal defect complicated pulmonary arterial hypertension surgical or transcatheter repair between 2012 and 2016.Amongst 38 children ventricular septal defect mean size was 10.92 ± 6.38mm. The mean systolic pressure in the right ventricle on Echocardiography was 55.42 ± 18.47 mmHg.&nbsp; Mean pulmonary arterial pressure by right heart catheterisation was 52.12 ± 29.44 mmHg.&nbsp; The mean end diastolic index for all children was registered as 76.78±19.58ml. Cardiac output was preserved in all children. In the pre-operative period, 9 of these children were treated with sildenafil.One week after the operation, mean right ventricle systolic pressure decreased as for children who did not receive preoperative sildenafil (from 55.5±14.8mmHg to 32.2±14.4mmHg) (p &lt;0.01), as for children who did (from 81.4±10.3mmHg. to 48.1±12.4mmHg (p value &lt; 0.01)). End diastolic index normalized in 92.5% of cases. Right ventricle systolic pressure decreased &gt;40% in all children a month after the surgery.In our study prescription of specific drug therapy of pulmonary arterial hypertension with the purpose of preparing for surgery has no effect on the effectiveness of surgical treatment of ventricular septal defect. We had had no early postoperative mortality.

A clinical case of radiofrequency pulmonary artery denervation for treatment of a patient with residual chronic thromboembolic pulmonary hypertension

Improving the methods of diagnosis, therapy and surgical treatment of chronic thromboembolic pulmonary hypertension (CTEPH) provides a complete cure in most cases. Data on the survival of CTELH patients is contradictory, and primarily due to the treatment availability. In Russian Federation there are few experienced centers performing thromboendarterectomy and balloon pulmonary angioplasty. Until recently, specific drug therapy was not available for most patients because of its high cost. The presented clinical case demonstrates modern opportunities of treatment of inoperable patients with residual CTEPH by the method of pulmonary artery denervation using a radiofrequency ablation.

Pulmonary Hypertension with Valvular Heart Disease: When to Treat the Valve Disease and When to Treat the Pulmonary Hypertension.

This article will review the current guidelines for therapeutic intervention in (pulmonary hypertension) PH related to left heart disease (PH-LHD). The 6th World Symposium on Pulmonary Hypertension (WSPH) recommended that the mean pulmonary artery pressure (mPAP) should be lowered to 20mmHg. In several randomized controlled trials performed in patients with PH-LHD, pulmonary arterial hypertension (PAH)-specific drug therapy demonstrated no evidence of beneficial effects. Furthermore, in the sildenafil for improving outcomes after valvular correction (SIOVAC) trial, the use of sildenafil in the context of PH post-valvular heart disease (VHD) intervention is associated with an increased risk of clinical deterioration and death. Therefore, medical therapy such as PAH-specific drugs is still not recommended in PH-LHD. The principle of PH-LHD therapy is the treatment of underlying VHD. It is crucial to undergo surgical intervention at an appropriate time prior the development of potentially irreversible PH. Stress echocardiography (SE) is helpful to define symptoms and can be useful to assess the systolic pulmonary artery pressure (SPAP) and stratify severity of VHD. This comprehensive review of the literature highlights the role of SE imaging to assess VHD and is needed for the asymptomatic patients with severe VHD or symptomatic patients with non-severe VHD in the context of PH-LHD. The focus of patient evaluation should be on identifying patients with significant underlying valvular heart disease and referring in a timely manner for VHD treatment per society guidelines as pharmacologic pulmonary vasodilator therapy for PH-LHD has not shown efficacy as seen in other forms of PH.

Myocardial infarction complicating blunt chest trauma: Case report and literature review

Myocardial infarction represents a mechanical complication of blunt chest trauma, a rare but life-threatening condition in which careful evaluation is mandatory. Early intervention is crucial, and coronary stenting or bypass graft surgery is described with generally satisfactory long-term outcomes. We present a 28-year-old man who developed extensive myocardial infarction and circulatory arrest after a blunt chest trauma in a professional water polo game. The cardiac computed tomography and the coronary angiography demonstrated left main artery dissection; the echocardiogram revealed anterior myocardial infarction with a severely decreased left ventricular ejection fraction, and the patient underwent coronary angioplasty with stent implantation. Six days later, he complained about chest pain due to acute stent thrombosis, and coronary artery bypass grafting was performed. Left ventricular heart failure was treated with specific heart failure drug therapy and a biventricular pacemaker and defibrillator. Ten years later, the patient has a good quality of life, is asymptomatic and works as a water polo coach under heart failure drug therapy and regular follow-up.

Sleep-Related Disorders in Neurology and Psychiatry.

Sleep-related disorders are a group of illnesses with marked effects on patients' quality of life and functional ability. Their diagnosis and treatment is a matter of common interest to multiple medical disciplines. This review is based on relevant publications retrieved by a selective search in PubMed (Medline) and on the guide- lines of the German Society for Sleep Medicine, the German Neurological Society, and the German Association for Psychiatry, Psychotherapy and Psychosomatics. A pragmatic classification of sleep disorders by their three chief complaints-insomnia, daytime somnolence, and sleep-associated motor phenomena-enables tentative diagnoses that are often highly accurate. Some of these disorders can be treated by primary care physicians, while others call for referral to a neurologist or psychiatrist with special experience in sleep medicine. For patients suffering from insomnia as a primary sleep disorder, rather than a symptom of another disease, meta-analyses have shown the efficacy of cognitive behavioral therapy, with high average effect sizes. These patients, like those suffering from secondary sleep disorders, can also benefit from drug treatment for a limited time. Studies have shown marked improvement of sleep latency and sleep duration from short-term treatment with benzodiazepines and Z-drugs (non- benzodiazepine agonists such as zolpidem and zopiclone), but not without a risk of tolerance and dependence. For sleep disorders with the other two main manifestations, specific drug therapy has been found to be beneficial. Sleep disorders in neurology and psychiatry are a heterogeneous group of disorders with diverse manifestations. Their proper diagnosis and treatment can help prevent secondary diseases and the worsening of concomitant conditions. Care structures for the treatment of sleep disorders should be further developed.

The therapeutic management of non-cognitive symptoms of dementia

It is estimated that, with the increase of the life expectancy of the population, one in two people at the age of 85 years old will have a form of dementia. This will represent a real burden for medical systems, and an increasing responsibility for their families and for society. The behavioral and psychological symptoms of dementia continue to receive insufficient attention. These symptoms can be observed some years before an adequate diagnosis of dementia, and they can be the first signs of alarm before the development of specific cognitive pathology. Patients suffering from dementia can benefit from integrated medical services, specialized care at home or at the hospital, day care services, specialized health services, memory assessment services, psychological and home care therapies, together with a specific drug therapy. Taking into account all of these aspects presented above, the aim of the paper is to analyze if an earlier diagnosis of dementia can be done in clinical practice, because the initiation of earlier treatment, in the mild-to-moderate phase, can lead to a considerable improvement of cognitive functions. In this context, as dementia is diagnosed earlier, an appropriate treatment can also improve the behavioral symptomatology. Also, a multidisciplinary approach can be of real help in assessing, anticipating and managing all these issues.

Association of Antihyperglycemic Therapy with Risk of Atrial Fibrillation and Stroke in Diabetic Patients

Type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Atrial fibrillation (AF) and stroke are both forms of CVD that have major consequences in terms of disabilities and death among patients with diabetes; however, they are less present in the preoccupations of scientific researchers as a primary endpoint of clinical trials. Several publications have found DM to be associated with a higher risk for both AF and stroke; some of the main drugs used for glycemic control have been found to carry either increased, or decreased risks for AF or for stroke in DM patients. Given the risk for thromboembolic cerebrovascular events seen in AF patients, the question arises as to whether stroke and AF occurring with modified incidences in diabetic individuals under therapy with various classes of antihyperglycemic medications are interrelated and should be considered as a whole. At present, the medical literature lacks studies specifically designed to investigate a cause–effect relationship between the incidences of AF and stroke driven by different antidiabetic agents. In default of such proof, we reviewed the existing evidence correlating the major classes of glucose-controlling drugs with their associated risks for AF and stroke; however, supplementary proof is needed to explore a hypothetically causal relationship between these two, both of which display peculiar features in the setting of specific drug therapies for glycemic control.

Clinical Nutrition in Critical Care Medicine – Guideline of the German Society for Nutritional Medicine (DGEM)

Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).

ACUTE KIDNEY INJURY DURING CRITICAL ILLNESS – A GLOBAL CHALLENGE

The report is devoted to the problem of acute kidney injury (AKI) in critically ill patients. Currently, the clinical definition of AKI is based on the assessment of increasing serum creatinine, but this method has a number of significant drawbacks. Perhaps the use of biomarkers for early detection of renal injury will improve diagnostic results. Up to date, no specific drug therapy for AKI has no available. The therapeutic tactics are based on the assessment of the risk of development AKI in critically ill patient, hemodynamic optimization, revision of drug therapy to exclude nephrotoxic drugs and the use of renal replacement therapy (RRT). Despite the numerous studies and the presence of multiple researches of AKI, there are many unclear issues related, for example, how to choose tactics of infusion therapy, the use of vasopressor support in patients with AKI, the time of the beginning and the choice of the mode of RRT, the feasibility of combining several technologies of extracorporeal hemocorrection. It is important to define how to improve the short-term prognosis and the long-term consequences of renal dysfunction.

One Size Does Not Fit All: The Case for Translational Medicine.

Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are integrated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunctional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.

Комментарии к рекомендациям EULAR/EFORT по лечению пациентов старше 50 лет с низкоэнергетическими переломами и профилактике у них повторных переломов

Osteoporosis is considered a serious public health and social concern that catches public attention worldwide. A set of recommendations for management of patients with fragility fractures were developed on an initiative of the European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopedics and Traumatology (EFORT) in December 2016. Authors have reviewed the recommendations through provision of health care practices in the Russian Federation. A protocol of hip fracture surgery within 48 hours of admission to trauma services for fragility cases represent a needful tool for optimization of medical care system. Specific techniques and implant designs for fracture fixation in osteoporotic bone are described with the focus on subsequent fractures prevention and fracture risk assessment. Effective rehabilitation is shown to rely on patient's understanding of the pathogenesis of the pathological process. Specific drug therapies and non-pharmacological treatment can be administered for osteoporotic patients with low-energy fractures.