Prospective Open-label Observational Study Research Articles

Evaluation of the efficacy and tolerability of naftidrofuryl in the therapy of chronic cerebral ischemia

Objective: to study the clinical efficacy and tolerability of naftidrofuryl (Duzofarm®) in patients with chronic cerebral ischemia (CCI).Patients and methods. A prospective open-label multicenter observational study evaluated the clinical efficiency and tolerability of naftidrofuryl treatment in patients with CCI. To statistically evaluate the efficacy and tolerability of naftidrofuryl, the investigators used data from 200 outpatients with Stages I–II CCI who were included in the program of treatment and received its full cycle. The patients were prescribed naftidrofuryl at a dose of 100 mg (2 tablets) thrice daily. Basic therapy that the patients had received before their inclusion in the observation program was not discontinued. The patients' status was evaluated using a specially designed questionnaire. Four visits were scheduled. All the patients underwent neurological examination. To study the patients' cognitive functions and emotional state, the investigators used the following tests and scales: the Mini-Cog test, the Mini-Mental State Examination (MMSE), the Zung Self-Rating Anxiety Scale, the Asthenia Subjective Assessment Scale, and the Modified Scoring Scale for Subjective Sleep Characteristics. Adverse reactions were recorded to evaluate the tolerability of therapy.Results and discussion. Naftidrofuryl therapy significantly improved health and reversed complaints in the patients. By the end of the treatment cycle, there was a significant improvement on all scales, which suggested a decrease in the severity of cognitive impairment and asthenic and mild anxiety disorders. When performing the Mini-Cog test, the proportion of patients who were able to remember and recall three words without errors increased from 43 to 86%, and when doing the clock drawing test, the proportion increased by 65%. Cognitive functions on the MMSE were observed to statistically significantly improve by 1.2 scores. According to the Zung Anxiety Self-Rating Scale, the number of patients with anxiety disorders decreased by 24%, those with insomnia significantly declined by 31% compared with the baseline level.Conclusion. The findings showed the high efficiency and appropriateness of naftidrofuryl administration to patients with Stages I–II CCI and hypertension.

Intranasal ketorolac, diagnosis, and desensitization for aspirin-exacerbated respiratory disease

BackgroundIntranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization. ObjectiveWe conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD. MethodsPatients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013. Participants selected either one of the following desensitization protocols: intranasal ketorolac 1 day before oral ASA (group 1, combined) or ketorolac challenge with greater than 2 weeks elapsing until oral ASA (group 2, washout). All patients were on a leukotriene-modifying drug (montelukast) for at least 1 week before the challenge. ResultsA total of 20 patients were enrolled: 13 in group 1 and 7 in group 2. No significant differences were seen for baseline symptom scores or forced expiratory volume in 1 second. Group 1 exhibited significant increases for the threshold dose of ASA (P = .009), the likelihood of having silent ASA desensitization (P = .01), and decreased reaction severity to oral ASA (P = .04). There were no significant differences in reaction forced expiratory volume in 1 second, the incidence of extrapulmonary symptoms, limited nasoocular reactions, rescue treatment requirements, or time to symptom resolution. There was 100% concordance between reactions to intranasal ketorolac and oral ASA for group 2, supporting its use as a diagnostic test for AERD. ConclusionIntranasal ketorolac is a useful diagnostic test and adjunct within the combined ketorolac/ASA protocol to achieve effective, efficient, and perhaps safer desensitization to ASA for patients with AERD.

Population Pharmacokinetics of Levetiracetam in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage Exhibiting Augmented Renal Clearance.

Patients with severe trauma exhibit augmented renal clearance, which can alter the dosing requirement of renally eliminated drugs. This study aimed to develop a population pharmacokinetic model for levetiracetam in patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage, and use it to describe optimal dosing regimens. This was a prospective open-label observational study. Critically ill adult patients with severe traumatic brain injury or aneurysmal subarachnoid hemorrhage without renal dysfunction and receiving levetiracetam were eligible. Serial levetiracetam plasma concentrations were analyzed to develop a population pharmacokinetic model and perform dosing simulations. A two-compartment model best described the concentration-time data from 30 patients. The mean ± standard deviation parameter estimates were bioavailability (F) of 0.8 ± 0.2, absorption rate constant of 2.4 ± 2 h-1, clearance 2.5 ± 1.1 L/h, central volume of distribution 8.9 ± 3.0 L/h, and transfer rate constraints of 1.8 ± 1.1 h-1 from central to peripheral compartments and 0.7 ± 0.3 h-1 from peripheral to central compartments. For the simulated intermittent dosing regimens, on average, the median trough concentration reduced by 50% for every 40-mL/min/1.73m2 increase in urinary creatinine clearance. Simulated doses of at least 6 g/day were required for some levels of augmented renal clearance. Patients with severe traumatic brain injury and aneurysmal subarachnoid hemorrhage with augmented renal clearance are at risk of not achieving target levetiracetam plasma concentrations. We suggest dose titration guided by measured creatinine clearance, and/or, therapeutic drug monitoring if available, to minimize the risk of seizures.

99 Newly approved IV acetaminophen in Canada: Should we switch from oral to IV? A systematic review

Abstract Background Acetaminophen is the most commonly used drug in children. In 2019, an IV formulation became available in Canada, but with a price tag >500 times higher than oral acetaminophen. Acetaminophen use has been growing in the US since its approval in 2011, leading to a significant health cost increase. Therefore, strict criteria for IV acetaminophen administration are needed to guide clinicians with a rational choice for route of administration and contain costs. Objectives To undertake a systematic review of available evidence comparing oral versus IV acetaminophen use in children. Design/Methods A systematic literature search was conducted on 5 databases until October 2019. All prospective interventional studies comparing IV to oral acetaminophen in patients <18 years old were included. Study selection, data collection and analysis were done according to PRISMA guidelines. Results Among 6417 abstracts, 29 full text articles were assessed, of which only 3 were retained. Indication for acetaminophen use in these studies was: analgesia (2 studies) and fever (1 study). Studies focused on: - Pharmacokinetics: In 2019, the first determination of oral bioavailability (F) of acetaminophen in children was reported in 47 stable PICU patients (microtracer study design with a population pharmacokinetic study). It showed an F=72% with a high inter-individual variability (range: 11%-91%). - Pharmacodynamics studies: • Analgesia: Analgesic efficacy after cleft palate repair was compared in 45 children (median age: 8 month) divided in three arms receiving either oral (15mg/kg every 6h), IV (12.5mg/kg every 6h) or placebo in a double-blind randomized controlled trial. No difference in pain scores and opioids requirements was found between the oral and IV acetaminophen groups. • Fever: An open-label prospective observational study reported the effect of IV (15mg/kg) versus oral acetaminophen (15mg/kg) on the evolution of temperature in children with fever >39.5°C in hospital and outpatient settings. Two hundred patients (mean age 6.7 years) were included in each arm. Temperature decreased quicker with IV administration but 4 hours after administration, temperature was similar in each group. Conclusion Despite the widespread use of IV acetaminophen, there is little evidence to suggest that it improves analgesia compared to the oral formulation. Similarly, fever weans faster but whether this translates into any meaningful clinical outcome is unknown. Available data is insufficient to guide clinicians with a rational choice of route of administration, but the significantly higher costs do not seem justified by the small (if any) benefits of IV vs oral acetaminophen.

Are Patients at Risk for Recurrent Disease Activity After Switching From Remicade® to Remsima®? An Observational Study.

Background: Since the late ‘90s, infliximab (Remicade®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima® were introduced in clinical practice.Aim: To investigate the interchangeability of Remicade® (originator infliximab) and its biosimilar Remsima® in patients with rare immune-mediated inflammatory diseases (IMIDs).Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade® to Remsima® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation.Results: Forty eight patients treated with Remicade® were switched to Remsima® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima® treatment, one withdrew from the study and one received additional corticosteroid therapy.Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade® to Remsima®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade® to Remsima®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening.

Predictive factors of adherence to an association of glucosamine sulfate, copper, and ginger extracts in patients with symptomatic osteoarthritis: a prospective open-label French noninterventional study (the PREDOA study).

Background: Osteoarthritis (OA) management needs a combination of nonpharmacological and pharmacological modalities. However, as in many chronic conditions, the main concern with OA therapy is the difficulty in obtaining good medication compliance over a long period. The PREDOA study aimed to investigate the predictive factors of adherence to treatment in patients with OA treated with glucosamine sulfate (GS)–copper sulfate–ginger root (GCu), a symptomatic slow-acting drug for OA.Methods: Ambulatory patients with a clinical diagnosis of OA were included in a prospective (6 months) multicenter open-label observational study. All patients received two capsules of GS-GCu once daily for 6 months. Demographics, disease features (OA location, symptom duration, concomitant therapies, comorbidities), and patient self-assessment of pain (0–10) were obtained at baseline. At month 6, the investigator collected patient self-assessments of treatment observance, reasons for nonadherence, pain scores, patient perceptions of treatment efficacy, changes in analgesic intake, and occurrence of adverse events. Predictors of observance were studied in univariate and multivariate analyses.Results: A total of 2,030 patients were included in the study. At baseline, the average pain score was 6.4±1.7. Observance was good in 80% of patients. It was weaker in active than retired patients (P=0.005) in patients not taking concomitant treatment (P=0.008) or who had never been treated for OA (P=0.001). Observance was correlated with pain decrease (P<0.0001) and with lack of adverse effects (P<0.001). Age, sex, pain level at baseline, OA location, and number of painful joints were not related to treatment compliance.Conclusion: Medication compliance with GS-GCu depends both on the safety–efficacy balance and several patient related-factors. To improve adherence, detailed information about therapeutic objectives is necessary in active patients who do not get any other medications and for whom it is their first treatment for OA.Clinical trial identifier: CCTIRS 14-371 B.

Why patients with multiple sclerosis perceive improvement of gait during treatment with natalizumab?

Gait impairment is one of the common manifestations of multiple sclerosis (MS) and contributes to a loss of quality of life. Natalizumab, an anti-α4 integrin monoclonal antibody, has been shown to have an effect in treatment of MS, reducing relapses and inflammatory lesions. Aim of our study was to assess how patients perceive gait impairment over the first year of treatment with natalizumab and what is the objective correlate of this change. This is an open-label prospective observational study. Subjective gait evaluation was measured by Multiple Sclerosis Walking Scale-12 (MSWS-12). Objective gait assessment included Timed 25-Foot Walk Test (T25FW) and spatiotemporal parameters of gait measured by a GAITRite instrument during a self-selected speed of walking (normal walk) and a fast speed of walking (fast walk). We analysed data of 50 patients with a relapsing-remitting form of MS, median EDSS 3.5 (range 1.5-5). MSWS-12 score significantly decreased between the baseline and month 12 of treatment (p < 0.001). Walking velocity and step length were significantly improved in Normal walk tests (p < 0.001). During the Fast walk tests, a step length and a double support time of the gait cycle were significantly improved (p = 0.001). Change in MSWS-12 score confirmed the clinically significant improvement of gait in patients with MS treated with natalizumab for 1 year. The analysis of spatiotemporal gait parameters has shown a significant improvement in self-selected gait velocity and step length.

Analysis of Hypersensitivity in Fragrance Series by Patch Testing.

Introduction:Allergic contact dermatitis (ACD) is an inflammatory disorder, which occurs as a result of repeated contact with an allergen. Fragrances are the products obtained naturally or produced synthetically. The purpose of this study is to detect the fragrance allergens producing ACD.Materials and Methods:This is an open-label prospective observational study. Patients of age above 18 years with history of using cosmetic products with dermatitis lesions over face, neck, axilla and hands were included. Patch testing was done with fragrance series by using the standard technique. The results were interpreted on day 2 and day 4 as recommended by International Contact Dermatitis Research Group criteria.Results:Totally 27 patients were included in this study. Of them, 12 were males and 15 were females; the mean age was 43 years. The mean duration of symptoms was 12.5 months. The most common site of involvement was hands. Housewives and office workers were the most commonly affected occupational groups. The most commonly used category of cosmetic product was talcum powders by 13 (48.1%) patients. In this study, 85.18% patients showed at least one fragrance antigen positivity. Fragrance mix II is the most frequent allergen in this study.Discussion:We conclude that the fragrance mix II is an important marker to find out fragrance allergy. Hand dermatitis is the most common presentation in patients with fragrance allergy. Perfumed talcum powders, soaps and perfumes are the leading sources of sensitization to fragrance allergens.

Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study

Background Abdominal aortic aneurysm (AAA) rupture is a common cause of sudden death. Pre-emptive elective surgical repair can prevent aneurysm rupture and be life-saving. Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation using magnetic resonance imaging (MRI) in patients with AAAs. For this reason, USPIO-enhanced MRI represents a promising new technique that could improve risk prediction and better guide surgical intervention. Objectives To assess whether or not USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes in patients with AAAs. Design A prospective multicentre open-label observational cohort study. Setting Three secondary and tertiary care hospitals in Scotland. Participants Patients (n = 342) aged &gt; 40 years with a maximum anteroposterior AAA diameter of ≥ 40 mm confirmed by abdominal ultrasonography, and under ultrasonographic surveillance as part of routine clinical care. Interventions USPIO-enhanced MRI of AAA. Main outcome measures The primary end point was the composite of aneurysm rupture or repair. Secondary outcomes included rate of aneurysm growth, all-cause mortality and aneurysm-related mortality. Results Participants (85% male, aged 73.1 ± 7.2 years) had a baseline aneurysm diameter of 49.6 ± 7.7 mm, and USPIO enhancement was identified in 146 participants (42.7%), absent in 191 participants (55.8%) and indeterminate in 5 participants (1.5%). During follow-up (1005 ± 280 days), there were 17 AAA ruptures (5.0%), 126 AAA repairs (36.8%) and 48 deaths (14.0%). Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1 ± 2.5 vs. 2.5 ± 2.4 mm/year; p = 0.0424), although this was not independent of current smoking habits (p = 0.1993). The primary end point (aneurysm rupture or repair) occurred more frequently in participants with USPIO enhancement [69/146 (47.3%) vs. 68/191 (35.6%), difference 11.7%, 95% confidence interval 1.1% to 22.2%; p = 0.0308]: this was similar for each component of rupture (6.8% vs. 3.7%; p = 0.1857) or repair (41.8% vs. 32.5%; p = 0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (p = 0.0275). Baseline AAA diameter (p &lt; 0.0001) and current smoking habits (p = 0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic 0.7935 to 0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with AAAs, and predicts the rate of aneurysm growth and clinical outcome. USPIO-enhanced MRI does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Larger trials are now needed to explore the prediction of emergent aneurysm events to establish the added benefit of USPIO-enhanced MRI. Comparative outcome studies should determine whether or not using other imaging biomarkers that track alternative disease processes have better predictive capability than USPIO-enhanced MRI. Trial registration Current Controlled Trials ISRCTN76413758. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

Everolimus in infants with tuberous sclerosis complex-related West syndrome: First results from a single-center prospective observational study.

Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged ≥2years with refractory TSC-associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC-associated WS are still lacking. Therefore, a prospective open-label observational study was initiated at our center, to evaluate everolimus add-on treatment in infants with TSC-associated WS, previously refractory to standard treatment. For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8-42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children. According to our preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC-associated WS, contributing to better developmental progress.

Ledipasvir and Sofosbuvir for untreated HCV genotype 1 infection in end stage renal disease patients: A prospective observational study.

Hepatitis C virus (HCV) infection in end stage renal disease (ESRD) is associated with increased mortality. Recently, numerous directly acting antiviral agents have been approved for the management of HCV. Ledipasvir along with Sofosbuvir has been approved for management of genotype 1 infection in patients with eGFR ≥30 mL/min. However, there is paucity of data regarding its role in the management of patients on dialysis. This is a single center prospective open label observational study to assess the safety and efficacy of Ledipasvir and Sofosbuvir in hemodialysis (HD) patients who were diagnosed with HCV genotype 1 infection. Eligibility criteria were treatment naive HD patients with normal liver histology. We administered Ledipasvir and Sofosbuvir combination tablet on alternate days for a period of 12 weeks. Primary efficacy end point was the assessment of sustained virological response (SVR12), and the safety end point was the discontinuation of therapy secondary to adverse drug effects. A total of 21 patients were treated with this regimen. Two patients expired during the study period and are not related to the therapy. SVR12 was achieved in all the 19 patients. None of the patients in our study discontinued the therapy or had severe adverse drug effects. One patient had head ache and another patient had giddiness which were managed symptomatically. Ledipasvir and Sofosbuvir combination therapy on alternate days, is effective even in ESRD patients, with excellent SVR12 rates, and it is as safe as in other population groups, without any major adverse reactions.

Change in Coefficient of Fatigability Following Rapid, Repetitive Movement Training in Post-Stroke Spastic Paresis: A Prospective Open-Label Observational Study

In post-stroke patients, the possibility of performing an active ankle dorsiflexion movement is favorable for the recovery of gait. Moreover, the fatigue due to repetitive active ankle dorsiflexion could reduce the speed gait. We assessed the change in coefficient of fatigability of active ankle dorsiflexion after a home-based self-rehabilitative procedure in post-stroke patients. In a prospective open-label observational study conducted in 2 university hospitals, a home-based self-rehabilitation treatment comprising two 12-minute sessions per day (3 times per week for 3 months) was performed by 10 outpatients with post-stroke lower limb impairment. Each session consisted of three 1-minute series of repeated active ankle dorsiflexion efforts at maximal speed on the paretic side, each one followed by 3-minute bouts of triceps surae stretch. Coefficients of fatigability of dorsiflexion and 10-meter barefoot ambulation speed were evaluated at baseline and at the end of the program. At 3 months of follow-up, there was a decrease in the coefficients of fatigability of ankle dorsiflexion, both with knee flexed and extended (respectively from 8% to 2% and from 6% to 2%; P < .01), associated with an increase in comfortable ambulation speed (from .24 to .26 m/s; P < .05). The reduction of coefficient of fatigability of ankle dorsiflexion, together with walking speed improvement, suggested the effectiveness of self-rehabilitation using alternated periods of self-stretch and rapid alternating efforts in the paretic lower limb after stroke.

Initial results of efficacy and safety of Sofosbuvir among Pakistani Population: A real life trial - Hepatitis Eradication Accuracy Trial of Sofosbuvir (HEATS).

Objective:The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 – 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir (Zoval) among Pakistani population with the rapid virologic response (RVR2/4 weeks) with HCV infections.Methods:This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir (Zoval) 400 mg plus ribavirin (with or without peg interferon) for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics.Results:A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 ± 11.41 years. Out of 573 patients 535 (93.3%) were treatment naive, 26 (4.5%) were relapser, 7 (1.2%) were non-responders and 5 (1.0%) were partial responders. A rapid virologic response was reported in 563(98.2%) of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated.Conclusion:Sofosbuvir (Zoval) is effective and well tolerated in combination with ribavirin in HCV infected patients.

Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks.

SEE LEONE AND PROIETTI CECCHINI DOI101093/AWW233 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Short-lasting unilateral neuralgiform headache attacks are primary headache disorders characterized by short-lasting attacks of unilateral pain accompanied by autonomic features. A small minority are refractory to medical treatment. Neuroimaging studies have suggested a role of the posterior hypothalamic region in their pathogenesis. Previous case reports on deep brain stimulation of this region, now understood to be the ventral tegmental area, for this disorder are limited to a total of three patients. We present a case series of 11 new patients treated with ventral tegmental area deep brain stimulation in an uncontrolled, open-label prospective observational study. Eleven patients with refractory short-lasting unilateral neuralgiform headache attacks underwent ipsilateral ventral tegmental area deep brain stimulation in a specialist unit. All patients had failed, or been denied access to, occipital nerve stimulation within the UK's National Health Service. Primary endpoint was change in mean daily attack frequency at final follow-up. Secondary outcomes included attack severity, attack duration, headache load (a composite score of attack frequency, severity and duration), quality of life measures, disability and affective scores. Information was also collected on adverse events. Eleven patients (six male) with a median age of 50 years (range 26-67) were implanted between 2009 and 2014. Median follow-up was 29 months (range 7-63). At final follow-up the median improvement in daily attack frequency was 78% (interquartile range 33%). Response rate (defined as at least a 50% improvement in daily attack frequency) was 82% and four patients were rendered pain-free for prolonged periods of time. Headache load improved by 99% (interquartile range 52%). Improvements were observed in a number of quality of life, disability and affect measures. Adverse events included mild incision site pain, subcutaneous displacement of the implantable pulse generator, transient oscillopsia and minor wound infection. One patient required removal of the system due to wound infection. Ventral tegmental area deep brain stimulation may be an effective treatment option for refractory short-lasting unilateral neuralgiform headache attack patients who have failed other therapies.

Comparison of doxycycline with azithromycin in treatment of pharyngeal chlamydia infection.

Recent data suggest that azithromycin may not be as effective as doxycycline in eradication of genital chlamydial infection. The aim of this study was to compare the eradication rate of pharyngeal Chlamydia trachomatis infection after treatment with azithromycin 1 g stat with that of doxycycline 100 mg twice a day for seven days. A prospective open-label observational study was conducted on patients with pharyngeal Chlamydia trachomatis diagnosed at Whittall Street Clinic, University Hospitals Birmingham, Birmingham, UK, between July 2012 and July 2013. We confirmed eradication of pharyngeal Chlamydia trachomatis with a negative test of cure. We treated all our patients with azithromycin 1 g stat until February 2013. At that stage, we offered doxycycline to patients with pharyngeal Chlamydia trachomatis A total of 398 patients (52 men, 346 women) were diagnosed with pharyngeal Chlamydia trachomatis during the study period. Of the 172 patients included in the final analysis, 78 were treated with azithromycin and 64 with doxycycline. Treatment failure was identified among 8/78 (10%) patients treated with azithromycin and 1/64 (2%) treated with doxycycline (absolute difference: 8 percentage points, 95% CI: 0-17%, p = 0.041). In our study, doxycycline 100 mg twice a day for seven days was associated with less treatment failure of oropharyngeal chlamydia compared with azithromycin 1 g stat Future randomised studies should investigate whether patients with pharyngeal Chlamydia trachomatis should be followed up with a test of cure when treated with azithromycin, or be treated with doxycycline.

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson’s disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs

BackgroundContinuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson’s disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. MethodsThe seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. ResultsMean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. ConclusionsCosts in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.

Single-Dose Fluconazole Therapy for Oral Thrush in Hospice and Palliative Medicine Patients.

Oral thrush is a common fungal infection of the mouth experienced by palliative medicine and hospice patients who have advanced cancer. Individuals often experience distressing symptoms that affect their oral intake with most regimens adding to pill burden. This is an open-label prospective observational study to assess the efficacy of a single-dose fluconazole 150 mg for oral thrush. Palliative medicine and hospice patients with a clinical diagnosis of oral thrush, a life expectancy of more than 1 week, and were able to swallow were enrolled. Signs and symptoms were evaluated on day 1 prior to administration of 150 mg of fluconazole and between days 3 to 5 after treatment. Of 57 patients, 55 (96.5%) had more than 50% improvement in signs and symptoms. Both the number and severity of symptoms changed significantly posttreatment ( P < .001). Side effects were few. Single-dose fluconazole 150 mg is an effective treatment of oral thrush for individuals with advanced cancer.

Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges.

Over 250 medical centers worldwide offer ketogenic diets to children with epilepsy; however, access to these therapies has been extremely limited for adults until recent years. We examine our 5-year experience creating and implementing a dedicated Adult Epilepsy Diet Center designed to provide adults with epilepsy access to ketogenic diets. Outpatients seen at the Johns Hopkins Adult Epilepsy Diet Center from August 2010 thru September 2015 age 18years and older were enrolled in a prospective open-label observational study. Patients that also enrolled in ongoing clinical diet trials were excluded from this study. Participant demographics, diet type, urine and/or serum ketones, laboratory studies, seizure frequency, diet duration, reason for discontinuing diet therapy, and side effects were recorded. A subgroup analysis of participants that met International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE) and were treated de novo with a Modified Atkins Diet (MAD) was performed to compare outcomes with the current literature regarding efficacy of other antiseizure treatments for DRE. Two hundred and twenty-nine adults attended the Adult Epilepsy Diet Center, and 168 met inclusion criteria. Two-thirds (n=113, 67%) were women with an age range of 18-86years at the initial visit. Thirty-five participants (21%, n=133) were already on a therapeutic diet while 79% (n=133) were naïve to diet therapy at the time of the initial visit. Diet-naïve participants were typically prescribed MAD (n=130, 98%), unless unable to intake adequate oral nutrition, in which case they were prescribed KD (n=1) or a combination of oral MAD and ketogenic formula (n=2). Twenty-nine of 130 (22%) participants prescribed MAD elected not to start or were lost to follow-up, and 101 (78%) began MAD. A subgroup analysis was performed on one hundred and six participants naïve to diet therapy that met International League Against Epilepsy criteria for DRE, were able to tolerate oral nutrition, and were prescribed a MAD. Relative to the number of enrolled participants who had reliable follow-up results for a given duration (including those that ultimately elected not to start or were later lost to follow-up), at 3months, 36% of these participants responded (≥50% seizure reduction) to diet therapy, and 16% were seizure-free. At 1year, 30% responded, and 13% were seizure-free. At 4years, 21% responded, and 7% were seizure-free. Hyperlipidemia was the most common side effect (occurring in 39% of screened participants, including those on a therapeutic diet prior to the initial visit). Weight loss was also common (occurring in 19% of all participants treated with a ketogenic diet therapy) yet was often an intended effect. This study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults, although long-term adherence was limited and further adequately controlled studies are necessary to determine the efficacy of ketogenic diets in the treatment of adults with epilepsy.

Comparison of cardiovascular safety of escitalopram and sertraline based on electrocardiographic alterations: a pharmacovigilance study

Background: Escitalopram and sertraline are the most commonly prescribed antidepressant drugs, belongs to SSRI class. Both the drugs are long been considered as free from cardiovascular adverse effects. Recently number of studies reported potential association between these drugs and pronounced cardiovascular adverse effects. ECG changes like prolongation of QT interval are frequently used as markers for the increased risk of a fatal cardiac arrhythmia. The potential cardiovascular adverse reaction profile of both these drugs is little studied in Indian rural population. Methods: This was a 6 weeks prospective open label observational study carried out in a drug naive 209 patients receiving either escitalopram (n=106) or sertraline (n=103). ECG parameters like heart rate, RR interval, PQ/PR interval, QRS duration and QTc interval, were obtained directly from the digital machine recordings, additionally the QT interval was measured manually with the help of caliper. Statistical analysis was done by using Statistical software SPSS 17.0. Results: Out of 209 drugs naive patients, 12 from escitalopram group and 10 patients from Sertraline were lost to follow-up. Hence ECG recordings of the remaining 94 patients under escitalopram group, 93 patients under sertraline group were used for study analysis. The ECG alterations caused by the escitalopram were compared with that caused by sertraline. It was observed that the differences between the ECG alterations caused by either of escitalopram or sertraline were statistically non-significant. Conclusions: It was concluded, at therapeutic doses neither of the drugs have the potential risk of drug induced arrhythmias, throughout the study.

PTH-067 An evaluation study of lactobacillus brevis cd2 in orofacial granuolomatosis

<h3>Introduction</h3> A small proportion of patients with Crohn’s disease develop orofacial granulomatosis (OFG), a rare, chronic disfiguring condition of unknown aetiology affecting the oral mucosa and perioral region. Previous studies have suggested that alterations in the oral microbiota may be involved in the pathogenesis of OFG. CD2 is a novel probiotic containing <i>Lactobacillus brevis</i>which has anti-inflammatory properties, primarily via reduced arginine availability. Previous studies have shown that CD2 reduces oral inflammation in chemotherapy-induced oral mucositis, Behcet’s disease and recurrent aphthous stomatitis. Our aim was to evaluate the tolerability and efficacy of CD2 lozenges in reducing oral inflammation in patients with active OFG. <h3>Method</h3> This was a single-centre prospective open-label observational study. Patients were recruited from a specialist OFG clinic between February and August 2014. Patients with active OFG received an eight week course of CD2 lozenges taken four times per day. Patients were reviewed before and after treatment and disease activity assessed by Oral disease activity score (ODAS), Visual analogue scale (VAS) of oral soreness and Global physician assessment (GPA). <h3>Results</h3> 28 patients were recruited with 4 patients withdrawing (3 non-compliance, 1 of which had severe learning difficulties; 1 re-classified as aphthous stomatitis). 7 patients failed follow-up leaving 17 patients (9 males) available for final analysis. The median age was 35 years (range 18–70 years) with 5/17 patients diagnosed with concurrent intestinal Crohn’s disease. Before treatment, the median ODAS was 12 (range 2–36), median VAS was 50% (range 0–90%), with 9/17 patients classified as having mild disease, 2/17 moderate and 6/17 severe. Post treatment, the median ODAS was 12 (range 1–34), median VAS was 20% (range 0–70%), with 9/14 patients had mild disease, 7/14 moderate and 1/14 severe. The reduction in the mean ODAS at 2 months was: 15.5–11.9 = 3.6 (p = 0.044). The mean improvement in oral soreness measured by VAS was: 44%–26% = 18% (p–0.003). There were no adverse events, however one patient discontinued treatment due to severe diarrhoea which resolved upon CD2 cessation. <h3>Conclusion</h3> CD2 appears to be safe, well-tolerated and of benefit in reducing oral inflammation and oral soreness in active OFG. Given the marked improvement in oral soreness, CD2 may have a role in symptom relief in other oral inflammatory conditions. Based on these results, a larger double-blind prospective study is recommended. The treatment shows promise as an adjunct to dietary therapy and an alternative to systemic immunosuppression. <h3>Disclosure of interest</h3> None Declared.