Likelihood Of Side Effects Research Articles

A Comparison of Traditional Chinese Medicine and Multiple Conventional Therapy in Treating Oral Lichen Planus: A Network Meta-analysis.

To evaluate and compare the efficacy of seven conventional treatments and traditional Chinese medicine (TCM) combined therapies for oral lichen planus. This study employs PubMed, Web of Science, Cochrane Library, and Cnki to collect studies. After evaluating the quality and bias risk, RevMan 5.4.1 and R Gemtc package was utilised with a visual analogue scale and side effects as outcomes, to compare the efficacy of the seven treatments. This study included 20 studies, with a sample size of 1669. Our results suggest that photodynamic therapy and TCM demonstrate the most significant decrease in visual analogue scale and the rank is as follows: photodynamic therapy > TCM > TCM combined with non-hormonal immunosuppressive drugs > TCM combined with glucocorticoids > chloroquine combined with glucocorticoids > non-hormonal immunosuppressive drugs > glucocorticoids. Among them, compared to glucocorticoids, photodynamic therapy (-1.55, 95% CI: (-3.09, -0.02)), TCM (-1.25, 95% CI: (-2.46, -0.06)) significantly outperform in statistics. Moreover, no side effects were reported by the photodynamic therapy treatment. In the comparison with non-hormonal immunosuppressive drugs, the result indicates TCM (-4.17, 95% CI (-8.24, -0.34)), glucocorticoids (-2.78, 95% CI (-5.69, -0.17)) and their combination (-2.83, 95% CI (-5.93, -0.05)) have a significantly lower probability of the appearance of side effects. This study indicates that TCM, from the perspectives of efficacy and the likelihood of side effects, outperforms all other common therapies, besides photodynamic therapy, in treating oral lichen planus.

E011 What information should we provide to inform and empower our patients to participate in shared decision making? The patient perspective

Abstract Background/Aims With an increasing number of biologic and targeted synthetic disease-modifying anti-rheumatic drugs and their biosimilar agents coming to the market, there is an increased choice of treatments available to patients. It is paramount to understand what information patients require to weigh up risks and benefits of each treatment to empower them to take part in shared decision making. This study aims to explore which factors (in addition to their clinical history) are deemed most important by patients when choosing a treatment and if they believe cost of treatment should be considered. Methods 74 randomly selected patients, who had been referred to the biologic or targeted synthetic treatment pathway, were invited to complete an anonymous online survey. Paper responses were also offered to patients who were unable to participate electronically, to avoid digital exclusivity. The survey consisted of 10 questions looking at patient perspectives questioning if they wanted to be involved in decisions about biologic and targeted synthetic treatment, which patient factors were important to them, if they considered cost as an important factor, if they would find a decision aid such as graphic/diagrams useful and if they would like a written record of how a shared decision was made. Results A total of 50 patients responded to the survey (40/50 online vs. 10/50 paper survey). 94% of patients stated that they would like to be involved in decisions about choice of biologic/ targeted synthetic medication. 58% said they think it is important to consider the cost of treatment. Based on the responses from the patients, the top patient factors (chosen by more than 60% of respondents) which were considered important are: how treatment is given, where treatment is given, how often it needs to be taken, how frequently monitoring is required, likelihood and severity of possible side effects. 66% of respondents said they would like to be shown a graphic/diagram to support their shared decision making and 80% of respondents said they would like a written record to explain how a shared decision was made about the best treatment for them. Conclusion The majority of patients included in our study would like to be actively involved in the shared decision-making process and would like to be given information such as route, frequency and location of administration, frequency of monitoring and severity and likelihood of side effects. The majority felt they would benefit from having a graphic/ diagram with all the relevant information summarised to help understand information easily. Providing a written record of the shared decision making will also make the process more transparent. Feedback from the survey has informed our service redesign, specifically our approach to shared decision making, to improve our patients’ experience. Disclosure N. Mathews: None. F. Ferris: None. A. Bayliss: None. E. McCormack: None. K. Summerhayes: None. H. De Vere: None. E. Rose-Parfitt: None.

Sex differences in drug effects and/or toxicity in oncology

The prevalence, incidence, and severity of a wide variety of diseases and ailments are significantly influenced by the significant disparities that occur between the sexes. The way that men and women react to pharmacological treatment also varies. Therefore, it is crucial to comprehend these reactions in order to conduct risk assessment correctly and to develop safe and efficient therapies. Even from that limited vantage point, the manner and timing of our drug usage might have unintended and unanticipated consequences. There are sex-specific differences in the incidence and mortality of certain malignancies. One of the most important discoveries in cancer epidemiology is the gender inequalities. Cancer incidence differences between the sexes are thought to be regulated at the genetic and molecular levels and by sex hormones like oestrogen. Differences based on sex and gender are among the least investigated factors impacting cancer susceptibility, progression, survival, and therapy response despite their established importance in clinical care. The molecular mechanisms underlying sex differences in particular are poorly known, hence the majority of precision medicine approaches employ mutational or other genetic data to assign therapy without taking into account how the patient's sex may affect therapeutic efficacy. In patients receiving chemotherapy, there are definite gender-dependent disparities in response rates and the likelihood of side effects. This review explores the influence of sex as a biological variable in drug effects or toxicity in oncology.

Does It Matter How You Ask? Assessing the Impact of Failure or Effectiveness Framing on Preferences for Antibiotic Treatments in a Discrete Choice Experiment.

Studies assessing framing effects in discrete choice experiments (DCE) primarily focused on attributes related to mortality/survival information. Little is known about framing effects for other attributes in health-related DCEs. This study aimed to investigate how framing treatment outcome as effective, failure, or a combined frame impacts respondent choices and DCE outcomes. Three Bayesian D-efficient designed DCE surveys measuring preferences for antibiotic treatments were randomly distributed to a representative sample of the Swedish population aged 18-65 years (n=1119). Antibiotic treatments were described using five attributes. Four attributes were static: Contribution to Antibiotic Resistance, Treatment Duration, Likelihood of Side-Effects, and Costs. A fifth treatment attribute was framed in three ways: Effectiveness, Failure Rate, or both. Mixed logit models were used to analyze attribute level estimates, importance value, and choice predictions. Significant differences between the frames were found for the parameter estimates of the attributes of Treatment Duration and Likelihood of Side-Effects, but not Treatment Outcome which was the alternatively framed attribute. Contribution to Antibiotic Resistance and Costs were the most important attributes for all participants regardless of framing. Choice predictions for the "best option" antibiotic only slightly differed between the groups based on the frame seen (95.2-92.4%). Our study showed that attribute framing can impact preferences regardless of the attribute's importance value in alternative valuation. However, the practical implication of this effect may be limited. A theoretical discussion is needed to identify how researchers should accommodate and report any potential framing effect in their studies.

Multimodal therapy for oligometastatic prostate cancer: results from a single-centre study

Introduction. In recent years, interest in the use of radical prostatectomy (RPE) as one of the components of a multimodal approach in patients with lymphogenous disseminated and metastatic prostate cancer (PCa) has grown significantly. At the same time, the dearth of large randomized trials does not make it possible to use this technique in wide clinical practice outside of clinical trials.Purpose of the study. To evaluate the effectiveness of multimodal therapy using combined chemo-hormonal, surgical and radiation therapy in patients with primary oligometastatic hormone-sensitive PCa.Material and methods. The study included 48 patients with primary oligometastatic prostate cancer who received combination treatment within the internal one-research-center protocol. At the first stage, all patients underwent combined drug therapy with docetaxel (75 mg/m2 intravenously every 3 weeks for 6 courses) and degarelix. Patients who had a decrease in PSA level ≤ 2 ng/ml and registered stabilization of the disease according to radiological examination were treated surgically through RPE with extended pelvic and retroperitoneal lymph node dissection. Radiation therapy was performed only in patients with the presence of bone lesions at a dose of 50-70 Gy to the location of bone metastases in the stage 3 plan of combined multimodal therapy.Results. PCa biochemical relapse was verified in 27 (56.3%) patients during the median follow-up of 10 months. The average time to PSA increase was 9.0 ± 5.7 months (from 1 to 24 months), median — 7 months, Six-month PSA relapse-free survival (PSA-RFS) was 61.2 ± 7.5%; 1-year PSA-RFS — 38.0 ± 8.6%. The average duration before the initiation of hormonal therapy was 12 ± 6.1 months (from 3 to 27 months), median: 10 months. Six-month survival before the drug administration was 72.6 ± 6.8%; twelve-month survival: 40.9 ± 8.7%. About 40% of patients with oligometastatic PCa had no signs of progression and did not receive any other drug therapy for 12 months after completion of protocol treatment.Conclusions. Analysis of the study results demonstrates satisfactory oncological outcomes of the studied treatment option in patients with newly diagnosed oligometastatic hormone-sensitive PCa, as well as a low likelihood of side effects and complications. Nevertheless, it is necessary to continue conducting larger and more structured randomized trials to determine the possibility of applying this therapeutic approach in clinical practice.

Elderly patient with coronary artery disease. What are common problems that need solving?

The health profile of elderly patients with coronary artery disease commonly includes comorbidities, polypharmacy, a high likelihood of side effects in drug interactions, depression, cognitive deficit, which inevitably affects the quality and effectiveness of drug therapy as well as adherence to the prescribed therapy. The risk of poor outcomes is less likely to be adequately assessed in elderly patients with coronary artery disease. They less often receive effective drug therapy to manage the risks. This article discusses the optimal selection of highly effective antianginal medical therapy aimed at preventing recurrent episodes of angina pectoris and improving the quality of life of an elderly patient with coronary artery disease.

Pharmacoepidemiology of Antiepileptic Drugs in Children

With the pharmacotherapy of epilepsy, there is a decrease in the number of seizures or their complete cessation. The aim of the study was to conduct a comparative analysis of the efficacy and safety of antiepileptics traditionally used in medicine (valproate, carbamazepine) and new-generation analogs (topiramate) in the treatment of epilepsy in children and adolescents. The study was conducted in 2014 and 2018, at the Center for Epileptology and Neurology, Moscow (Russian Federation). In 2014, 777 medical records of children registered with epilep¬tologists were studied, in 2018 - 840 medical records of children. The age interval of 3 months is 18 years. Favorable outcomes of epilepsy therapy with different drugs were calculated, with different approaches monotherapy and polytherapy. A favorable outcome meant remis¬sion, which lasted more than 1 year and more than 3 years. In 2014 and 2018, monotherapy prevailed among the treatment methods. With monotherapy, valproates are used more often (up to 70%), carbamazepine is used 3.0 times less often (p ≤ 0.01 relative to valproates). The use of topiramate is 10 times less than the number of valproate therapy (p ≤ 0.0001), and barbiturates - 15 times (p ≤ 0.0001). Among the new gen¬eration drugs, topiramate was often used, with monotherapy, with symptomatic forms of epilepsy (10.4% in 2014 and 7.9% in 2018, p ≤ 0.05), as well as with a cryptogenic form (9.6% and 4.4%, respectively, p ≤ 0.05). The chosen type of therapy can significantly affect the number of side effects. With polytherapy, in 2014, side effects were observed in 44.1% compared with monotherapy (18.1%, at p ≤ 0.01), in 2018 - 45.1% against 20.9% (at p ≤ 0.01). Topiramate showed lower efficacy compared with carbamazepine in all years of the study with monother¬apy (0.65, at p ≤ 0.04). The results did not confirm the effectiveness of the new drugs. There was no difference in efficacy and safety between traditional drugs (valproate, carbamazepine) and new generation drugs (topiramate and others). In 2014 and 2018, monotherapy (72.8%) over polytherapy (27.2%) prevailed among the treatment methods for epilepsy. Among the drugs, valproate was predominant (65.8%), and in all identified forms of epilepsy. The new generation of drugs did not show statistically significant advantages compared to traditionally used ones. The method of polytherapy of epilepsy in children gives a twofold increase in the likelihood of side effects (p ≤ 0.01).

Проблема побочных эффектов антиретровирусных препаратов при ВИЧ-инфекции.

Антиретровирусная терапия применяемая в настоящее время перевела ВИЧ инфекцию в разряд хронических контролируемых инфекций и продлила жизнь и качество жизни. Однако любой антиретровирусный препарат вызывает побочные эффекты, хотя не у всех и не всегда одинаковые. На основе анализа литературных данных оценить современное состояние проблемы побочных явлений антиретровирусной терапии у ВИЧ инфицированных пациентов. Ниже приводятся данные о побочных эффектах различных групп антиретровирусных препаратов, применяемых в прошлом и в настоящее время, а также отдельных их представителей. Антиретровирусные препараты проявляют различные побочные эффекты, в частности, митохондриальная токсичность, вызванная нуклеозидных ингибиторов обратной транскриптазы (НИОТ), вызывает широкий спектр побочных эффектов, таких как лактоацидоз, стеатоз печени, миопатия, кардиомиопатия, периферическая невропатия, панкреатит и, возможно, синдром липодистрофии. В целом, ингибиторы интегразы хорошо переносятся и вызывают минимальные лекарственные взаимодействия. Применение прежних антиретровирусных препаратов было связано с целым рядом побочных явлений, который включает в себя лактоацидоз, стеатоз печени, аллергические реакции, миопатию, кардиомиопатию, периферическую нейропатию, панкреатит и липоатрофия и т.д., эти побочные эффекты реже встречаются у новых, рекомендуемых АРВ препаратов. При лечении необходимо учитывать вероятность возникновения побочных эффектов и возможности их предотвращения.

Features of the composition of certain complex hyperosmolar infusion solutions

Objective. To justify the use of complex hyperosmolar solutions.
 Results and discussion. Today, the question of the qualitative composition and quantitative relationship between the various components of infusion-transfusion therapy remains controversial. Hypertonic solutions in various concentrations of NaCl were first used for “low-volume resuscitation” in patients with hemorrhagic shock. Administration of these solutions results in a temporary osmotic pressure gradient between the blood plasma and the interstitial space, causing fluid to move into the intravascular space, increasing cardiac output, blood pressure, and improving microcirculation. Recently, combinations of hypertonic NaCl with colloids, as well as multicomponent infusion drugs are increasingly used. These are, in particular, the drugs Rheosorbilact, Xylate, Lactoxyl, Sorbilact, Lactoprotein with sorbitol, Gecoton developed at the Institute of Blood Pathology and Transfusion Medicine of the National Academy of Medical Sciences of Ukraine. Preparations based on polyhydric alcohols of sorbitol or xylitol, alkalizing agents of sodium lactate or sodium acetate and electrolytes. Rheosorbilact, Xylate, Lactoxyl are basic solutions for detoxification therapy, including in patients with diabetes. Sorbilact used as an osmodiuretic and for the treatment of patients in the postoperative period. Protein-salt solution based on donor albumin Lactoprotein with sorbitol is a mean for intensive care in emergencies. Colloid-hyperosmolar infusion solution Gecoton based on hydroxyethyl starch is used as a mean for low-volume resuscitation in the prehospital stage, including combat victims. Specially selected substances comprising the combined drugs affect different parts of the pathological process and have several advantages compared to mono-drugs. The pharmacological action of such solutions is due to the mutual potentiation of the action of its components. This provides hemodynamic effect and can reduce the dosage of each component separately, reducing the likelihood of side effects. The use of multicomponent hyperosmolar solutions can significantly reduce the total volume of fluid administered to patients.
 Conclusions. Complete hyperosmolar drugs can be recommended for routine and auxiliary fluid therapy and treatment for emergency conditions.

Therapeutic drug monitoring (TDM) in treatment of a pregnant for 34 weeks with a diagnosis of gangrenous appendicitis, peritonitis

This article describes the clinical case of acute gangrenous appendicitis in a pregnant woman, followed by antibiotic therapy with meropenem dose of 2 g I. V. q8h with therapeutic drug monitoring (TDM) management. Therapeutic drug monitoring may be helpful for special patient populations with large pharmacokinetic variability, which include pregnant women. The goal of therapeutic drug monitoring is to increase the effectiveness of therapy by adjusting the dose and dosage regimen, as well as reducing the likelihood of side effects.

My new normal: A patient's perspective on polymyalgia rheumatica

My new normal: A patient's perspective on polymyalgia rheumatica

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review.

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β-amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.

EFFECTS OF SMOKING ON THE DISEASE PROGNOSIS IN CANCER PATIENTS

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.

P058 LOW DOSE METHOTREXATE HAS SIMILAR OUTCOMES AS HIGH-DOSE METHOTREXATE IN COMBINATION WITH ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASES

Methotrexate (MTX) is a well-known immunomodulator in the treatment of inflammatory bowel disease (IBD) and often combined with biological agents. The ideal MTX dose for combination therapy has not been determined. Our aim is to investigate the effect of varying doses of MTX when used with anti-TNF agents in IBD on efficacy and safety outcomes. This study included patients with Crohn’s disease (CD) or ulcerative colitis (UC) receiving care between January 2005 and June 2018. Low-dose MTX was defined as ≤15mg/week and high-dose as >15mg/week. The primary efficacy outcome was a composite of need for IBD-related hospitalization or surgery, steroid initiation, or change of biologic agent within 1 year. Safety outcomes included side effects related to MTX, serious infections, malignancy and need to discontinue MTX therapy within 1 year. Multivariable logistic regression models adjusting for relevant covariates examined the independent association between MTX dose and outcomes. Our study included 222 patients with IBD (163 CD, 59 UC). Just over half were receiving low dose MTX (51%). We found no difference in gender, IBD type, disease location and behavior, disease duration, prior IBD treatments, serum albumin and CRP between the two groups. The primary efficacy composite outcome was noted in 51 patients (47%) in the high dose MTX group compared to 47 patients (42%) in the low-dose MTX group (p=0.436). After adjusting for relevant confounders, there remained no difference in primary outcome between the two dose groups of MTX (OR 0.62, 95% CI 0.31 – 1.24, p=0.179). Separately, we also observed no difference in hospitalization, surgery or steroid initiation within 1 year between the low-dose and high-dose MTX groups (Figure 1). MTX dosage was not associated with likelihood of side effects (high dose 22.9% vs low dose 27.4%, p=0.44). A total of 20 serious infections (9%) were reported during the first year of combination therapy but there was no significant difference between high versus low dose MTX (9.2% vs. 8.9%, p=0.93). We found no significant associations with MTX dose and any side effect (OR 1.34, 95% CI 0.67 – 2.70, p=0.410) or development of serious infections (OR 0.97, 95% CI 0.35 – 2.67, p=0.946). Two cases developed a malignancy (thyroid carcinoma and hepatocellular carcinoma) during the first year of combination therapy, both in the high dose MTX group. Discontinuation of MTX therapy occurred in one fourth of the low dose MTX patients (24.8%) and 29.5% in patients with high dose MTX (p=0.442). Low dose and high dose MTX combination therapy were equally effective and no difference in infection and malignancy rates was observed. There is an important need for prospective trials comparing low and high dose MTX when used in combination with biologic therapy to determine optimal dosing. Figure 1. Comparison of safety (a) and efficacy (b) outcomes between low dose MTX and high dose MTX combination therapy

A modern view on diagnostics and treatment of onychomycoses (literature review)

This article provides an overview of current data on the diagnosis and treatment of onychomycosis. Fungal infection is the cause of 50 % to 60 % of all nail diseases. In other cases, nail diseases are non-fungal in nature and are caused by various pathological processes, including chronic and infectious skin diseases, chronic somatic lesions, endocrine and psychological disorders caused by hereditary, occupational and traumatic factors. Onychomycosis constitutes a significant part of the pathology of nails, according to numerous researchers, onychomycosis accounts for about 20 % of all diseases of the nails. Known pathogens of onychomycosis are usually divided into three groups: dermatophytes, yeast-like fungi of the Candida species, and mold fungi. According to preliminary studies, dermatophytic onychomycosis accounts for up to 83 % of all infectious lesions of the feet nails and more than 50 % of the nails of the hands. Mixed infections are becoming increasingly important in the etiology of onychomycosis. Data has appeared on mixed dermatophytic-bacterial and dermatophytic-viral onychomycoses. Laboratory diagnostics are based on traditional methods: microscopic examination of pathological material and cultural studies, as well as modern methods (PCR diagnostics). Molecular genetic research showed the high sensitivity of this PCR method, which allows researchers to confirm the diagnosis of onychomycosis in just a day and reveals a larger percentage of patients with onychomycosis compared to traditional methods were able to, thus this indicates the need to revise existing approaches to laboratory diagnosis. Currently, there are a large number of methods for treating onychomycosis. Etiotropic therapy is the only effective approach in the onychomycosis treatment. The main types of therapy are local therapy, systemic and combined. Higher therapeutic efficacy of combination therapy is associated with different routes of antifungal drugs, their synergistic action, the possibility of using drugs with various differing mechanisms of action and, consequently, the expansion of the spectrum of action, the creation of a high concentration of antifungal drugs in the nail plate and surrounding tissues, and the removal of a significant mass of the spreading infectious agent. In addition, the advantage of combination therapy in the treatment of onychomycosis is shorter therapy duration, and therefore a reduction in the likelihood of side effects, as well as epidemiological and economic efficiency, and a high cosmetic effect. Key words: onychomycosis, polymerase chain reaction, systemic and topical antimycotics, combination therapy. For citation: Kutasevych YF, Oliinyk IO, Ishcheikin KY, Bilozorov OP, Mashtakova IO, Zimina TV, Suprun KH, Chekhovska HS. A modern view on diagnostics and treatment of onychomycoses (literature review). Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(3):313–20

Abstract IA11: Chemoprevention in hereditary GI cancer syndromes

Abstract IA11: Chemoprevention in hereditary GI cancer syndromes

Repeat RF Ablation of C2 and Third Occipital Nerves for Recurrent Occipital Neuralgia and Cervicogenic Headaches

Objective: To address the degree and duration of pain relief from recurrent cervicogenic headaches and/or occipital neuralgia following retreatment with radiofrequency ablation of the C2 dorsal root ganglion and/or third occipital nerves; to review outcomes including duration and degree of pain relief; to evaluate procedure’s complication rate and patient’s willingness to repeat the procedure; to compare effectiveness of the most recent RF ablation to patient’s first RF ablation. Methods: This is a single-center retrospective observational study of 23 patients with recurrent cervicogenic headaches and/or occipital neuralgia treated with repeated RF ablation of the C2 dorsal root ganglion and/or third occipital nerves. All patients receiving treatment from January 2010 to July 2014 are included in this single site retrospective study. This is an IRB approved medical chart review study. Results: 22 of 23 patients underwent follow-up. An average of 86.5% of participants reported pain relief on average of 25.4 weeks at time of follow-up. 41% reported side effects including suboccipital hyperesthesia and/or ear discomfort, 95% reported willingness to repeat the procedure again if severe symptoms recurred, 59% of patients reported the most recent RF ablation had the same results as the first, 32% reported the most recent RF was the most effective, and 9% reported that the first RF was the most effective. Conclusion: Repeated RF ablation is a feasible option for recurrent cervicogenic headaches and/or occipital neuralgia. Effectiveness of repeat intervention is the same or better than the first ablation. Though there was a higher likelihood of side effects including suboccipital neuralgia and/or ear discomfort on repeat treatment, the side effects were generally well tolerated.

Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review

Objective To perform a meta-analysis examining the efficacy of phytoestrogens for the relief of menopausal symptoms.Methods Medline, Cochrane, EMBASE, and Google Scholar databases were searched until September 30, 2013 using the following key words: vasomotor symptoms, menopausal symptoms, phytoestrogens, isoflavones, coumestrol, soy, red clover. Inclusion criteria were (1) randomized controlled trial (RCT), (2) perimenopausal or postmenopausal women experiencing menopausal symptoms, (3) intervention with an oral phytoestrogen. Outcome measures included Kupperman index (KI) changes, daily hot flush frequency, and the likelihood of side-effects.Results Of 543 potentially relevant studies identified, 15 RCTs meeting the inclusion criteria were included. The mean age of the subjects ranged from 49 to 58.3 and 48 to 60.1 years, respectively, in the placebo and phytoestrogen groups. The number of participants ranged from 30 to 252, and the intervention periods ranged from 3 to 12 months. Meta-analysis of the seven studies that reported KI data indicated no significant treatment effect of phytoestrogen as compared to placebo (pooled mean difference = 6.44, p = 0.110). Meta-analysis of the ten studies that reported hot flush data indicated that phytoestrogens result in a significantly greater reduction in hot flush frequency compared to placebo (pooled mean difference = 0.89, p < 0.005). Meta-analysis of the five studies that reported side-effect data showed no significant difference between the two groups (p = 0.175).Conclusion Phytoestrogens appear to reduce the frequency of hot flushes in menopausal women, without serious side-effects.

The Influence of Gene Polymorphism OPRM1 118A/G on the Perception of Pain and Pharmacodynamics of Narcotic Analgesics

The polymorphism of μ-opioid receptor is one of the most studied polymorphisms that affect the activity of narcotic analgesics. Despite that there are a large number of publications dealing with the problem, the obtained results are not being currently used in clinical practice. The purpose of this review is to describe the impact of this polymorphism on the perception of pain and sensitivity to narcotic analgesics. It is shown that patients with the G118G genotype of μ-opioid receptor are tolerant to narcotic analgesics and need a larger dose to achieve the desired effect than that in normal genotype. At the same time, the likelihood of side effects associated with the use of narcotic analgesics does not significantly differ between the carriers of normal genotype and those of the A118G, G118G genotypes.

Treatment of MuSK-Associated Myasthenia Gravis

Approximately 5-8% of myasthenia gravis (MG) patients test positive for antibodies against muscle- specific tyrosine kinase (MuSK) receptors. Except in extremely rare reports, all are acetylcholine receptor (AChR) antibody-negative. While MuSK myasthenia gravis (MMG) patients have distinct clinical phenotypes and may differ from AChR-positive patients in diagnostic testing and response to treatment, goals for the treatment of MMG are similar to those in non-MMG. Priority of treatment should be directed toward reducing weakness as much and as quickly as possible. This is particularly true in patients with bulbar or respiratory weakness in order to avoid progression to respiratory failure. After this initial phase, medications should be slowly tapered to the minimum effective dose. Considering the natural history of MMG, a small proportion of patients can be completely taken off treatment at some point, but the vast majority will require treatment for life. Response to acetylcholinesterase inhibitors (ACEi) is usually poor, and the likelihood of side effects is relatively high. However, considering the benign nature of this line of treatment and the potential for rapid response, an initial trial of ACEi is reasonable. Unless clearly contraindicated by other medical conditions, we recommend initiating corticosteroid treatment for all MMG patients, starting at a dose of 1.5-2mg /kg/ day of prednisone, followed by gradual and slow taper to the minimum effective dose. A steroid-sparing agent such as azathioprine - and, less often, mycophenolate mofetil or cyclosporine - may be added. When prednisone is used in combination with another immunosuppressive agent, reducing and then tapering off prednisone may be tried after maximum improvement is achieved. It should be emphasized that response to immunosuppressive medications can be delayed for months, although most patients eventually show marked and sustained response. Cyclophosphamide may be used sparingly in select patients who do not respond to the above medications. Rituximab has shown promising results in MMG, and should be considered in severe and refractory cases or in situations where other options are contraindicated or not tolerated by patients. Acute exacerbations may be treated by plasma exchange, which most reports indicate is superior to IVIg, although IVIg may still be used. To date, there is no convincing evidence for the role of thymectomy in MMG.