Third Month Of Treatment Research Articles

Evaluation of Sexual Dysfunction, Lower Urinary Tract Symptoms and Quality of Life in Men With Obstructive Sleep Apnea Syndrome and the Efficacy of Continuous Positive Airway Pressure Therapy

ObjectiveTo determine the presence of lower urinary tract symptoms (LUTS), nocturia, sexual dysfunction (SD), and the status of quality of life (QOL) in men with obstructive sleep apnea syndrome (OSAS) and after continuous positive airway pressure (CPAP) treatment, the changes in the presence of these conditions and the improvements of QOL. Materials and MethodsIn this study, 126 patients with suspicious diagnosis of OSAS were enrolled prospectively. International Prostate Symptom Score (IPSS), International Consultation on Incontinence Questionnaire-Male LUTS (ICIQ-MLUTS), Overactive Bladder Symptoms Score (OABS-V8), Nocturia Quality of Life (Nqol), voiding diary, International Index of Erectile Function (IIEF-15) questionnaire, and Short form 36 (SF-36) to assess the presence of SD, LUTS, nocturia, and the status of QOL were filled by patients before polysomnography. The same forms were filled in the third month of treatment by the patients directed to CPAP treatment due to moderate and severe OSAS. ResultsThere were significant differences in IPSS, IIEF, OABSS, ICIQ-MLUTS, Nqol and SF-36 scores, frequency of nocturia, and night-time urine volume according to OSAS severity. Among the factors affecting the QOL, there was strong correlation between ED and SF-36 sub-domains compared with the other factors. After CPAP treatment significant changes and improvements on these symptoms and QOL were observed. ConclusionIn patient with OSAS, the severity of SD and LUTS and their effect on QOL differ according to the severity of OSAS and CPAP treatment improves the negative impact of these conditions on QOL.

Efficacy of physical therapy associated with botulinum toxin type A on functional performance in post-stroke spasticity: A randomized, double-blinded, placebo-controlled trial.

The aim was to investigate if botulinum toxin type A (BTx-A) associated with physical therapy is superior to physical therapy alone in post stroke spasticity. A randomized, double-blinded controlled trial was performed in a rehabilitation unit on Northeastern, Brazil. Patients with post stroke spasticity were enrolled either to BTx-A injections and a pre-defined program of physical therapy or saline injections plus physical therapy. Primary endpoint was functional performance evaluated through time up and go test, six minutes walking test and Fugl-Meyer scale for upper limb. Secondary endpoint was spasticity improvement. Confidence interval was considered at 95%. Although there was a significant decrease in upper limbs flexor tonus (P<0.05) in the BTx-A group, there was no difference regarding functional performance after 9 months of treatment. When analyzing gait speed and performance, both groups showed a significant improvement in the third month of treatment, however it was not sustained over time. Although BTx-A shows superiority to improve muscle tone, physical therapy is the cornerstone to improve function in the upper limbs of post stroke patients.

Blood neutrophil-to-lymphocyte ratio is associated with prognosis in advanced gastrointestinal stromal tumors treated with imatinib.

Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of this study was to asses a clinical value of this ratio in patients with advanced GIST. Between 2001 and 2016, 385 patients with metastatic/unresectable GIST treated initially with imatinib were included in the analysis. In all patients, the NLR was assessed at the baseline, after 3 months of treatment, and upon disease progression (or last observation). The cutoff values for NLR were set at 2.7 and 5.4. Kaplan-Meier survival probability estimation with log-rank test and Cox proportional hazards model were used for analysis. Median progression-free survival (PFS) on imatinib treatment was 44.8 months, 5-year rate 43%; median overall survival (OS) 87.2 months, 10-year rate 36.3%. NLR >2.7 at baseline was significantly associated with poorer OS and PFS: median OS was 89.3 months (95% confidence interval [CI] 80.2-115) for NLR ratio ≤2.7 vs 59.4 months (95% CI 48.6-82) for NLR >2.7 (p < .001); median PFS was 59.4 vs 32.7 (p < .001), respectively. In multivariate model adjusted for mitotic index and driver mutation in the tumor (KIT exon 11 mutation versus other), NLR ratio was proven to be statistically significant (hazard ratio 1.09; 95% CI 1.01-1.19; p = .030). Among patients with disease progression, NLR >2.7 assessed at the third month of treatment was linked with significantly shorter median time to progression (7.5 vs 19 months). Our results demonstrate the usefulness of NLR as a prognostic and predictive marker as well as a marker for treatment monitoring in patients with advanced GIST treated with imatinib.

Transcranial Magnetic Stimulation for Migraine Prevention in Adolescents: A Pilot Open‐Label Study

To assess the feasibility, tolerability, and patient acceptability of single-pulse transcranial magnetic stimulation (sTMS) for migraine prevention in adolescents in an open-label pilot study. Migraine is common in adolescents and can be disabling. Well tolerated preventative therapies that are safe and effective are needed. This was an open-label prospective pilot feasibility study of sTMS for migraine prevention in adolescents aged 12-17 years. Participants used sTMS twice daily in a preventative fashion, as well as additional pulses as needed acutely. A 4-week baseline run-in period (weeks 1-4) was followed by a 12-week treatment period. Feasibility was the primary outcome. Secondary outcomes included tolerability and acceptability, as well as the change in headache days, number of moderate/severe headache days, days of acute medication use, and PedMIDAS (headache disability) scores between the run-in period (weeks 1-4) and the third month of treatment (weeks 13-16). Twenty-one participants enrolled. Nineteen completed the baseline run-in, and 12 completed the study. Using sTMS proved feasible and acceptable with overall high compliance once treatment administration was streamlined. Initially, for preventive treatment, participants were asked to give 2 pulses, wait 15 minutes, then give 2 additional pulses twice daily. This 15-minute delay proved challenging for adolescents, particularly on school days, and therefore was dropped. Study completion rate went from 4/13 (31%) to 7/8 (88%) once this change was made, P = .024. On average, participants used the device preventively between 22 and 24 days over a 28-day block. There were no serious adverse events. Two participants reported mild discomfort with device use. sTMS appears to be a feasible, well-tolerated, and acceptable nonpharmacologic preventive treatment for migraine in adolescents. In designing future trials of sTMS for migraine prevention in adolescents, streamlined treatment administration will be essential to minimize drop-out. Efficacy needs to be assessed in a larger trial.

Collyres de sérum autologue : traitement à long-terme dans le syndrome sec oculaire

Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid. This is a monocentric retrospective observational study conducted on 47patients, with 83eyes treated with autologous serum eye drops for isolated or secondary dry eye disease at the Marseille Public Hospitals between April 2014and April 2017. The patients' subjective symptoms (ocular surface disease index [OSDI] score), their degree of satisfaction and the side effects were collected using questionnaires. Tear Break Up Time (BUT) and Schirmer scores were noted. A clinical evaluation based on fluorescein staining (Oxford score) was carried out prior to treatment with AST at P0followed by 5periods: P1 (between 1and 3months), P2 (3to 9months), P3 (9to 15months), P4 (15months to 24months), and P5 (>24months). Out of the 83eyes treated, the mean age was 54.39±21.56. There were 20males (42.55%) and 27females (57.44%); treatment indications consisted mainly of 25.53% GVH, 21.27% severe dry eye disease and 19.14% Sjögren syndrome. The mean duration of follow-up was 9.82months±15.50. The OSDI score decreased by 19.32points±29.37 (P<0.05) between P0and P1and by 23.06points±18.41 (P<0.05) between P0and P4. The Oxford clinical score showed a significant decrease by the third month of treatment, between P0and P2, by 1.32points±1.76 (P<0.05). The Schirmer test and the BUT also showed an improvement in dry eye symptoms over time with AST, significantly at P1 (P<0.05). Complementary biological analyzes on the composition of AST are under way in order to identify predictive factors of effectiveness; patients not responding to AST treatment might respond to allogeneic serum from healthy donor cord blood. On this first series of 83eyes treated with ASD, clinical efficacy was noted in most of the patients. No infectious complications were reported, and the satisfaction rate was very high.

Response of Blood Parameters to CPAP Treatment in Patients with Obstructive Sleep Apnea.

Many studies have evaluated the relationship between the NLR and PLR in patients with obstructive sleep apnea (OSA), and have shown that they are related to inflammation. We evaluated whether 3 months of continuous positive airway pressure (CPAP) treatment in patients with moderate to severe OSA without any comorbidities would affect the NLR and PLR values. Full blood count parameters were evaluated before and after 3 months of CPAP treatment in patients with a diagnosis of moderate to severe OSA without any comorbidities. Twenty-nine patients (18 [62.1%] males) were enrolled. The mean body mass index (BMI) was 34.85±5.75 kg/m2, the apnea-hypopnea index score was 49.85±27.42, and CPAP was 9.34±1.77. No significant change in BMI was observed after the third month of treatment. Although the Epworth Sleepiness Scale (ESS) score decreased significantly (p=0.000), no changes were observed in the NLR, PLR, or C-reactive protein level (p>0.05). Mean platelet volume and red blood cell distribution width changed significantly after treatment (p=0.01; p<0.001). The NLR and PLR did not change after CPAP treatment in patients with moderate to severe OSA without any comorbidities.

Correlation between individual inflammation genetic profile and platelet rich plasma efficacy in hair follicle regeneration: a pilot study reveals prognostic value of IL-1a polymorphism.

Hair loss generates severe psychosocial implications. To date, exploring the prognostic factors of possible clinical benefit of autologous blood concentrate platelet rich plasma (PRP) was failed. The aim of our pilot study was to explore the correlation between the individual inflammation genetic profile and PRP efficacy in the treatment of hair follicle regeneration. 41 volunteers (25 men, 16 women) took part in this retrospective study. All the patients were scheduled for 4 sessions of PRP application with intervals of 40-60 days. All the patients were checked up at 6 weekly intervals for 6 months and, then, at the end of the first year. A panel of 5 polymorphisms on 4 genes (IL-1a, IL-1b, IL-6, and IL-10) implicated in the individual genetic inflammation profile were performed. A significant increase rate in hair density was noticed after the third month of treatment in 32/41 (78%) of the subjects. We found an interesting association between the pro-inflammatory cytokine IL-1α polymorphism C>A (rs17561) and responders to PRP treatment. The cases carrying C/C genotype (coding for Ser114) were 21 (66%) in responders and only 2 (22%) in non-responders (p<0.05). In addition, about IL-1a, the frequency of G/G genotype in responder patients was over two times lower in responder (31%) than in non-responder patients (78%). Our pilot study demonstrated a correlation between the individual genetic inflammatory profile and the efficacy of the PRP treatment in males. On the contrary, in females, it showed a negative correlation. IL-1a could be used as a prognostic value for PRP efficacy. Also, these results provide preliminary evidence that may encourage the design of controlled clinical trials to properly test this modus operandi on a large number of subjects.

DEVELOPMENT AND VALIDATION OF CARBAMAZEPINE PLASMA CONCENTRATIONS MEASUREMENT AND ITS APPLICATION ON EPILEPSY PATIENTS

Objective: To develop and validate high-performance liquid chromatography with photodiode array (HPLC-PDA) detector as a method for measuring carbamazepine plasma concentrations in epilepsy patients treated with monotherapy or polytherapy.Methods: Carbamazepine was extracted from epilepsy patients’ plasma through liquid-liquid extraction, using protein precipitation with chloroform. Analysis was performed using HPLC with Inertsil DS-4 C18 (4.6x150 mm), 5 μm particle size column. The optimal condition for separation was established in a mobile phase consisting of acetonitrile: water (50:50) at a flow rate of 1.0 ml/min, detected by PDA detector at 220 nm. Propylparaben was used as the internal standard. The retention time was 3.5 min.Results: Linearity was obtained over a concentration range of 0.5-16 μg/ml with r = 0.999. The method showed good intra-and inter-day precision and accuracy of more than 90% difference (% diff) and 95% relative standard deviation (RSD). Lower limit of quantification (LOQ) was 0.5 μg/ml and lower limit of detection (LOD) was 0.2 μg/ml with 100% accuracy and more than 90% precision. Recovery test was nearly 100%. Stability of carbamazepine plasma concentration in 3 epilepsy patients was measured on the first and third month of treatment, ranging between 83.5 to 98.7%. When used to compare carbamazepine as a monotherapy versus polytherapy, the method showed good selectivity.Conclusion: The present HPLC method was valid for measuring carbamazepine plasma concentrations in epilepsy patients treated with monotherapy or polytherapy. This method meets the standard in the EMEA guideline in terms of linearity, precision, and accuracy, also selectivity in epilepsy patients treated with polytherapy.

Anti-TNF-α effects on anemia in rheumatoid and psoriatic arthritis.

A key role in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) is played by inflammatory cytokines, including tumor necrosis factor-α (TNF-α), which are also involved in inducing inflammatory anemia. We have followed 67 RA patients and 64 PsA patients for 1 year to evaluate the effects of TNF-α inhibitors on disease activity and on inflammatory anemia. Patients were divided into three different treatment groups, according to a randomized assignment to receive therapy with etanercept, adalimumab, or infliximab. Treatment with anti-TNF-α resulted in a significant reduction in disease activity score-28 (DAS28) values both in RA and PsA patients, already from the third month of treatment (P = 0.01). In both populations, there was an increase in hemoglobin (HB) levels already after 3 months of treatment (P = 0.001), and HB levels were inversely proportional to the disease activity, regardless of the type of medication used. The increased HB values and the reduction of DAS28 values during the observation period suggest the existence of a negative correlation between them both in RA and PsA, regardless of the type of anti-TNF-α used. Our data suggest a pleiotropic action of anti-TNF-α, such as the well-known action on the activity of the disease, and the improvement in inflammatory anemia.

Correlation between entecavir penetration in peripheral blood mononuclear cells and HBV DNA decay during treatment of HBeAg-negative chronic hepatitis B.

Recently, due to its high effectiveness and tolerability, the treatment of chronic hepatitis B with entecavir became a standard practice. However, limited knowledge is currently available about its pharmacokinetic behaviour and intracellular disposition. Recently, our group reported an inverse correlation between entecavir plasma concentrations and the HBV DNA decay at the first and third month of treatment, respectively. In this paper we investigated the penetration of entecavir in peripheral blood mononuclear cells (PBMC) and in plasma, in order to evaluate the relationship between intracellular penetration and response, in a cohort of naive patients with hepatitis B e antigen (HBeAg)-negative CHB. Thirty-three patients were prospectively enrolled and gave written informed consent: the monitoring of clinical parameters (for example, HBV DNA, hepatitis B surface antigen [HBsAg], alanine aminotransferase) was carried out at the baseline and then monthly. Entecavir intra-PBMC and plasma trough concentrations were measured at 1 month of treatment, through a validated method based on liquid chromatography coupled with tandem mass spectrometry. While plasma entecavir analysis confirmed previous evidence of inverse correlation between drug concentrations and HBV DNA decrease after 3 months of treatment (r=-0.723; P<0.001), this correlation was not significant for intra-PBMC concentrations. When the intracellular disposition ratio (intra-PBMC/plasma concentration ratio) was considered, it showed a direct and significant correlation with HBV DNA decay at the third month (r=0.485; P=0.004). These results suggest that the antiviral activity of entecavir is dependent on its intracellular uptake, thus resulting in lower plasma concentrations in patients who have a marked HBV DNA decrease during treatment.

The efficacy of low-dose tadalafil in patients undergoing hemodialysis with end-stage renal disease

Background: Erectile dysfunction (ED) is a disorder that is frequently observed in people with chronic kidney disease who undergo hemodialysis (HD). In the context of evidence-based medicine, we aimed to investigate the effect of low-dose tadalafil on sexual function in patients undergoing HD.Methods: The medical records of 30 males (aged 29–65 years) with end-stage renal disease (ESRD) on a HD program, and who had received 5 mg tadalafil twice weekly, were retrospectively evaluated. Changes in erectile and ejaculatory function were evaluated using the International Erectile Function Index questionnaire, the Erection Hardness Scale (EHS), and the Male Sexual Health Questionnaire (MSHQ).Results: The mean age of the patients was 47.6 ± 10.1 years, their mean body mass index was 24.3 ± 4.2 kg/m2, their mean hemoglobin was 11.9 ± 0.9 g/dL, and their mean creatinine clearance was 5.8 ± 1.1 mL/min. At the third month of treatment, 36.6% of the patients had no ED, 40% had mild ED, 10% had mild-to-moderate ED, and 13.3% had moderate ED. The mean MSHQ scores (p < .05) and the mean EHS scores (p = .001) were significantly improved. There was no significant difference between Beck's Depression Inventory scores (p > .05), but Hamilton anxiety rate scores decreased significantly (p = .001). The quality-of-life score improved throughout the study period (p < .05).Conclusions: Tadalafil therapy is an effective therapeutic option in patients with ESRD who undergo HD, not only for the treatment of ED, but also for ejaculatory function, with acceptable adverse effects.

A Triple Blinded, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Oral Vancomycin in Primary Sclerosing Cholangitis: a Pilot Study.

Recent studies have suggested the therapeutic effect of antimicrobial agents on primary sclerosing cholangitis (PSC). Therefore, we aimed to evaluate the efficacy of oral vancomycin in patients with PSC. A triple blinded, randomized, placebo-controlled trial was performed on 29 patients (2015-2016) in the Imam Khomeini Hospital, Tehran, Iran (NCT02605213). Patients were divided into two groups by simple randomization method: placebo 11 (37.9%)/vancomycin 18 (62.1%) and were treated with oral vancomycin (125 mg, four times a day) for 12 weeks. All patients in both groups simultaneously underwent treatment with ursodeoxycholic acid (UDCA, 300 mg, three times a day) before and during the study. Patients' laboratory data and clinical symptoms were recorded at the beginning, first and third month after starting treatment, and the response to treatment was analyzed. 29 patients with a mean age of 36.27+/-10.60 years were included in the study. Primary endpoints were accomplished in the vancomycin group showing a significant decline in the mean level of PSC Mayo risk score (decrease rate 3rd month - baseline = -322.03%, p=0.026) during follow up time. Moreover, the analysis of the level of alkaline phosphatase (ALP) in the vancomycin group showed a significant decrease in the third month of treatment as compared to its level in the first month (mean difference 3rd month -1st month = -142.92, Decrease rate= -18.24%, p=0.02). Among secondary endpoints, erythrocyte sedimentation rate (p=0.005), gamma-glutamyl transpeptidase (p=0.02) and patients' symptoms including fatigue, pruritus, diarrhea and anorexia showed a significant decrease in the vancomycin group. This study demonstrated an acceptable efficacy of vancomycin in the treatment of PSC.

Role Of Various Factors In The Treatment Of Optic Neuritis----A Study

Aim: To analyse the influence of various factors on the visual outcome of Optic neuritis patients Materials & Methods: A total of 116 patients with optic neuritis were studied as a prospective study for two years in the department of Ophthalmology, Dr PSIMS&RF, Chinoutpalli. All cases were investigated for visual acuity, colour vision, APD, visual fields. At the end of the study all the above parameters were recorded and analysed. Discussion: All the patients having optic neuritis were presented with defective vision[100%].70 cases had ocular pain[60.34%].32 patients had defective colour vision[27.58%].28 patients had defective visual fields[24.14%].The study showed a female preponderance with 64% of cases. History of recurrence was noted in 10% of cases. Conclusion: In our study no specific factor is associated with the aetiology of optic neuritis.18% of cases showed bilaterality. After treatment[ONTT],all the cases showed significant improvement in the visual acuity. Colour vision was improved at the end of third month of treatment. ONTT regime has a very significant role in the treatment of Optic neuritis cases.

New inflammatory parameters in laryngopharyngeal reflux.

To investigate new inflammatory markers in patients with laryngopharyngeal reflux and determine whether these inflammatory parameters change in response to laryngopharyngeal reflux treatment. Complete blood count was evaluated to obtain platelet count and mean platelet volume and calculate neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Laryngopharyngeal reflux patients underwent three-month lansoprazole treatment. The study included 45 laryngopharyngeal reflux patients (9 men (20 per cent); mean age, 37.4 ± 11.6 years) and 35 healthy age- and sex-matched controls (7 men (20 per cent); mean age, 38.6 ± 8.9 years). The study group had significantly higher platelet-to-lymphocyte ratios and lower mean platelet volumes than the control group (p = 0.004 and p = 0.047, respectively). There was a significant correlation between platelet-to-lymphocyte ratios and initial inflammatory symptoms (reflux symptom index, p = 0.025; reflux finding score, p = 0.013). There was also a significant correlation between mean platelet volume increase and symptom resolution in the first and third months of treatment (p = 0.04 and p = 0.03, respectively). Platelet-to-lymphocyte ratio, a new inflammatory marker of chronic inflammation, was significantly higher in laryngopharyngeal reflux patients. Moreover, these patients had significantly lower mean platelet volume values, which increased with post-treatment symptom improvement.

Tocilizumab treatment in childhood Takayasu arteritis: Case series of four patients and systematic review of the literature.

Our aim was to describe our experience with tocilizumab (interleukin 6 receptor antagonist) treatment in children with Takayasu arteritis and to review previous studies regarding tocilizumab use in Takayasu arteritis patients. We reviewed the charts of all pediatric Takayasu arteritis patients followed up between 2000 and 2015 in Department of Pediatric Rheumatology in Hacettepe University, Ankara, Turkey, and we present the patients who were treated with tocilizumab. We screened PubMed and MEDLINE for articles involving Takayasu arteritis patients treated with tocilizumab. We have followed four pediatric Takayasu arteritis patients who received tocilizumab. The median duration of immunosuppressive treatment before tocilizumab onset was 16 (1-60) months. The median duration of tocilizumab treatment was 9.5 (7-13) months. One of our patients received tocilizumab as a first line immunosuppressive treatment directly after methylprednisolone. Others were resistant to their initial immunosuppressive treatment (cyclophosphamide, methotrexate, or azathioprine). All achieved complete response to tocilizumab at the third month of treatment. None of the patients reported any adverse events during the follow-up. In literature review, we identified 19 articles describing 75 Takayasu arteritis patients treated with tocilizumab. Eight of these received tocilizumab before the age of 18 years. Tocilizumab was the first line immunosuppressive treatment in six patients (five adults and one child). Our small series suggests that tocilizumab may be a promising alternative for Takayasu arteritis treatment. Long-term controlled studies are warranted to provide better evidence for tocilizumab treatment in childhood Takayasu arteritis.

Thyroid Hormone Replacement Therapy Improves Olfaction and Taste Sensitivity in Primary Hypothyroid Patients: A Prospective Randomised Clinical Trial.

Smell and taste are known to be influenced by thyroid function changes. However, many hypothyroid patients and physicians are unaware of their dysosmia and dysgeusia. The present study was performed to shed more light on the relation between hypothyroidism and olfactory loss. 32 primary hypothyroid patients and 31 controls enrolled in the prospective randomized interventional study. Newly diagnosed Primary hypothyroid patients were treated with L-thyroxine for 3-6 months. The control group was selected on the basis of the biochemical evidence of a normal thyroid function. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Smell identification, threshold, discrimination, TDI scores, bitter and sweet taste scores were significantly lower in untreated hypothyroid patients compared to controls (12.31±1.09 vs. 14.03±1.05, p<0.001; 7.09±1.15 vs. 8.89±1.12, p<0.001; 11.47±0.95 vs. 13.06±0.85, p<0.001; 30.90±2.70 vs. 35.89±2.07, p<0.001; 4.88±1.6 vs. 6.64±0.96, p<0.001; and 5.5±2.22 vs. 6.58±1.28, p=0.021) respectively. Comparison of scores at the third month of treatment and before treatment of hypothyroid patients revealed significant improvement in smell and taste functions in terms of identification, threshold, discrimination, TDI scores, bitter, sweet and salty tastes (12.31±1.09 vs. 13.84±1.22, p<0.001; 7.09±1.15 vs. 8.02±1.16, p<0.001; 11.47±0.95 vs. 12.41±1.21, p<0.001; 30.90±2.70 vs. 34.27±3.25, p<0.001; 4.88±1.6 vs. 6.06±1.4, p<0.001; 5.5±2.22 vs. 6.38±1.28, p<0.001; and 6.12±2.32 vs. 6.62±1.48, p=0.044) respectively. On correlation analysis, there was a negative correlation between TPO-Ab levels and discrimination, identification and TDI scores (r=-0.409, p=0.02; r=-0.424, p=0.016; r=-0.532, p=0.002), and also between Tg-Ab levels and identification, TDI, and bitter scores (r=-0.423, p=0.016; r=-0.468, p=0.007; r=-0.409, p=0.02) respectively. Primary hypothyroidism was found to have a negative effect on smell and taste. RAI treatment was found to be most destructive on smell and taste compared to surgical and autoimmune hypothyroidism. Treatment of hypothyroidism was positively correlated with an improvement of both senses. Thus, the future workup of patients with smell/taste loss should include investigations for thyroid functions.

Evaluation of the effectiveness and safety of glucocorticoids intravitreal implant therapy in macular edema due to retinal vein occlusion.

The purpose of this study was to evaluate the impact of intravitreal dexamethasone implant (Ozurdex) on macular morphology and functions in eyes with macular edema (ME) secondary to retinal vein occlusion. Efficacy outcomes of the treatment were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety outcomes were intraocular pressure and cornea endothelial cell density. The study was conducted by the prospective analysis on 36 patients (17 women and 19 men) aged 28–77 years (the average age was 58±15 years) treated with the injection of dexamethasone implant because of the persistent ME at the Department of Ophthalmology and Ophthalmology Outpatient Clinic of the University Centre of Ophthalmology and Oncology in Katowice. The studied group included 16 patients with central retinal vein occlusion (16 eyes), and 20 patients with branch retinal vein occlusion (20 eyes). We found a significant increase of BCVA after first, second, and third month of treatment. Six months after the treatment, BCVA decreased, although not significantly compared with the value obtained in the third month. Two months after the intravitreal implantation of dexamethasone delivery system, CRT was 338±163 μm and was significantly lower compared with pretreatment value. Between third and sixth month after the treatment, we found insignificant increase of CRT compared with thickness observed in second month. Two months after the treatment, we found an increase in intraocular pressure in 36% of cases and a further decrease during the final visit 6 months after the treatment. During the treatment, there were no significant differences in endothelial cell density in branch retinal vein occlusion and central retinal vein occlusion. We found the intravitreal dexamethasone implant to be safe, well tolerated, and likely to lead to fast morphological and functional improvement of the macula and visual rehabilitation in patients with ME due to retinal vein occlusion.

Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial.

Objective: To assess efficacy and safety of trigeminal neurostimulation with a supraorbital transcutaneous stimulator (Cefaly, STX-Med., Herstal, Belgium) in migraine prevention. Methods: This was a double-blinded, randomized, sham-controlled trial conducted at 5 Belgian tertiary headache clinics. After a 1-month run-in, patients with at least 2 migraine attacks/month were randomized 1:1 to verum or sham stimulation, and applied the stimulator daily for 20 minutes during 3 months. Primary outcome measures were change in monthly migraine days and 50% responder rate. Results: Sixty-seven patients were randomized and included in the intention-to-treat analysis. Between run-in and third month of treatment, the mean number of migraine days decreased significantly in the verum (6.94 vs 4.88; p = 0.023), but not in the sham group (6.54 vs 6.22; p = 0.608). The 50% responder rate was significantly greater ( p = 0.023) in the verum (38.1%) than in the sham group (12.1%). Monthly migraine attacks ( p = 0.044), monthly headache days ( p = 0.041), and monthly acute antimigraine drug intake ( p = 0.007) were also significantly reduced in the verum but not in the sham group. There were no adverse events in either group. Conclusions: Supraorbital transcutaneous stimulation with the device used in this trial is effective and safe as a preventive therapy for migraine. The therapeutic gain (26%) is within the range of those reported for other preventive drug and nondrug antimigraine treatments. Classification of evidence: This study provides Class III evidence that treatment with a supraorbital transcutaneous stimulator is effective and safe as a preventive therapy for migraine.

Metabolic parameters in patients with major depression treated with escitalopram

Objective: The aim of this study is to determine the change in metabolic parameters of patients with major depression treated with escitalopram. Methods: The height, body weight, waist circumference, blood pressure, lipid profile (total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides), fasting blood glucose, thyroid stimulating hormone and Hamilton Depression Scale (HamD) of 41 consecutively selected patients with major depression were measured before treatment and in the third month of treatment, for whom a decision to start treatment with escitalopram was decided. The relationship between treatment and changes in these metabolic parameters were evaluated at the end of this period. Results: The mean age of patients was 30.24±9.96 years. Eleven (27%) patients were male and 30 (73%) were female. Twelve (29.3%) patients were treated with 10 mg/day escitalopram, and 29 patients (70.7%) 20 mg/day. Significant increases were detected in body weight, body mass index, waist circumference and systolic blood pressures of all patients from initiation of treatment to three months. A significant increase was found in the waist circumference of male patients (n=11) after twelve weeks of treatment. Body weight, body mass index, waist circumference, triglycerides, systolic blood pressure were found to be significantly increased after three months of treatment in female patients (n=30) who were treated with escitalopram. HamD scores were found to be significantly decreased after three months in patients treated with escitalopram. Conclusion: Escitalopram caused an increase in especially body weight and waist circumference in patients with major depression.

Ruxolitinib Efficacy and Safety in Myelofibrosis: A Multicenter Observational Study

PATIENTS AND METHODSA multicenter observational study was conducted in patients with myelofibrosis receiving ruxolitinib. Data regarding disease characteristics, dosage, safety and efficacy of ruxolitinib were collected retrospectively.A total of 73 patients, diagnosed between 2002 and 2014 in 10 clinical sites, were included in the analysis. The male:female ratio was 2:1, median age at diagnosis was 64 years (range 27 to 82) and median duration of ruxolitinib therapy was 14 months. The study expands over 376.7 patient-years of observation, including 94.4 patient-years while on ruxolitinib.RESULTSThe diagnosis, revisited according to the WHO 2008 criteria, was primary myelofibrosis in 61%, post-essential thrombocythemia myelofibrosis in 21% and post-polycythemia vera myelofibrosis in 17% of patients. Median time from diagnosis till onset of ruxolitinib was 2.97 years. At the beginning of ruxolitinib treatment, the international prognostic scoring system (IPSS) risk category was low (3%), intermediate-1 (30%), intermediate-2 (42%), high (25%). Ruxolitinib starting dose was 5mg (18%), 10mg (20%), 15mg (30%), 20mg (32%) twice daily (BID).Response was defined as reduction in spleen size and disappearance of constitutional symptoms. The mean spleen size -measured in centimeters below left costal margin- was reduced from 10.8cm ± 1.6 (95% CI - confidence interval) at the beginning of ruxolitinib, to 6.6cm ±1.5 after 3 months and further to 4.5cm ±3.0 after 12 months of treatment. The reduction in spleen size after 3 months of treatment, expressed as percentage change from baseline tends to be higher with higher starting dose: 33% with 5mg BID, 29% with 10mg BID, 54% with 15mg BID and 59% with 20mg BID. At the onset of ruxolitinib, 77% of patients experienced constitutional symptoms. At 1 and 3 months of treatment the percentage fell to 30% and 15.5% respectively. On ruxolitinib dose of 20mg BID, the presence of constitutional symptoms rapidly declined from 84% to 18% after the first month of treatment. On the lower dose of 5mg BID, 67% of patients remained with symptoms after one month (p=0.02), but that proportion fell down to 18% by the third month of treatment with the same dose.Ruxolitinib was well tolerated without any non-hematological adverse events in 85.1% of patients at the beginning of therapy and in 90.2% after 3 months. Gastro-intestinal symptoms were the main complain in 6% of patients at the beginning of therapy, which disappeared by the third month of treatment. Any other non-hematological adverse event accounted for less than 2% each.Hematological parameters were affected by ruxolitinib therapy. Thrombocytopenia of all grades was present in 30% of patients at the beginning of treatment, in 52% at 3 months, and 59% at 12 months of treatment. Grade 3 and 4 thrombocytopenia was present in 7%, 14% and 18% respectively. The respective median platelet counts were 201000/μL, 125000/μL and 115000/μL.The dose of ruxolitinib remained stable in half the patients and was modified in the rest. Of those starting with 5mg BID, 60% remained in that dose, and 20% had their dose increased. Of those starting with 10mg BID, 67% remained stable, and 25% had their dose increased. Of those on 15mg BID, 53% remained in the same dose and 32% had their dose decreased. The majority (68%) of patients starting with 20mg BID, had their dose decreased. Dose modifications of ruxolinitib at 1, 3, 6, 12 months of treatment were not correlated with statistically significant changes in spleen size at the same time points (p-values: 0.4, 0.8, 0.8, 0.6 respectively).Permanent discontinuation of ruxolitinib occured in 16.7% of patients for the following reasons: side effects (including anemia, thrombocytopenia, investigator decision, patient preference) in 8.3%, progressive disease (including one death) in 5% and no response in 3.3% of the patients.CONCLUSIONSRuxolitinib can effectively improve splenomegaly and alleviate constitutional symptoms in patients with myelofibrosis. The symptoms are relieved slower with the low dosage, whereas the main side effect is thrombocytopenia. It can however be maintained within safety limits (grade < 3), with dose modifications without hampering efficacy. DisclosuresNo relevant conflicts of interest to declare.