Observer-blinded Clinical Trial Research Articles

A phase II clinical trial of a Vi-DT typhoid conjugate vaccine in healthy Indonesian adolescents and adults: one-month evaluation of safety and immunogenicity

BackgroundTyphoid fever is commonly found until today, especially in developing countries. It has fatal complications and measures must be taken to reduce the incidence of typhoid. Vaccinations are a key factor in prevention. This is a phase II randomized observer-blind clinical trial on a novel Vi-DT conjugate vaccine on 200 subjects 12 to 40 years of age.MethodsSubjects were screened for eligibility after which a blood sample was taken and one dose of vaccine was administered. Investigational vaccine used was Vi-DT and control was Vi-PS. Twenty-eight days after vaccination, subjects visited for providing blood sample to assess immunogenicity and were asked about local and systemic adverse reactions that occurred in the first 28 days.ResultsSubjects had minor adverse reactions. Pain was the most common local reaction. Muscle pain was the most common systemic reaction. There were no serious adverse events up to 28 days post vaccination. Seroconversion rates were 100% in the Vi-DT group and 95.96% in the Vi-PS group. Post vaccination GMTs were increased in both groups but it was significantly higher in the Vi-DT group (p < 0.001).ConclusionsVi-DT typhoid conjugate vaccine is safe and immunogenic in healthy Indonesian subjects 12 to 40 years.Trial registrationApproved by ClinicalTrials.gov. Clinical trial registration number: NCT03460405. Registered on 09/03/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03460405.

Safety and immunogenicity of a respiratory syncytial virus prefusion F protein (RSVPreF3) candidate vaccine in older Japanese adults: A phase I, randomized, observer-blind clinical trial

BackgroundRespiratory syncytial virus (RSV) causes lower respiratory tract infection, with a high burden of disease among adults ≥60 years. This study assessed the safety, reactogenicity, and immunogenicity of an investigational adjuvanted RSV vaccine (RSVPreF3/AS01B) in Japanese adults aged 60–80 years. MethodsForty participants were randomized to receive two doses of RSVPreF3/AS01B or the placebo, in a 1:1 ratio, two months apart, in this placebo-controlled study. Solicited administration-site and systemic adverse events (AEs) were collected within 7 days and unsolicited AEs within 30 days post-vaccination. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected throughout the study (12 months post-dose 2). RSVPreF3-specific immunoglobulin G (IgG) antibody concentrations and neutralizing antibody (nAb) titers against RSV-A were evaluated on day (D)1, D31, D61, D91 and those against RSV-B on D1, D31, D91. ResultsSolicited AEs were reported more frequently in RSVPreF3/AS01B recipients (80.0%–90.0%) than in placebo recipients (10.0%–20.0%). Two RSVPreF3/AS01B recipients experienced grade 3 solicited AEs. Rate of unsolicited AEs were similar (30.0%–35.0%) in both groups. No RSVPreF3/AS01B recipient reported SAEs/pIMDs, while one placebo recipient reported two SAEs that were unrelated to vaccination. Baseline RSVPreF3-specific IgG and RSV-A/-B nAb levels were above the assay cut-off values. In the RSVPreF3/AS01B group, RSVPreF3-specific IgG concentrations increased 12.8-fold on D31 and 9.2-fold on D91 versus baseline while nAb titers increased 7.3-fold (RSV-A) and 8.4-fold (RSV-B) on D31 and 6.3-fold (RSV-A) and 9.9-fold (RSV-B) on D91. ConclusionsThe RSVPreF3/AS01B vaccine was well tolerated and immunogenic in older Japanese adults. Clinical trial registration numberNCT04090658.

The safety and immunogenicity of a combined pertussis containing vaccine Tdap for HIV infected pregnant women and their newborns (WoMANPOWER) – A study protocol for a randomized clinical trial

Background: Globally there are an estimated 24.1 million cases and 160,700 deaths from pertussis annually in children under five years. The disease burden is higher in low- and middle-income countries, especially the African region, which contributes the largest proportions of cases and deaths. Immunization against pertussis in pregnancy is a recommended strategy for the prevention of infant pertussis in many high-income countries. However, vaccine immunogenicity and effectiveness may be different in immunocompromised individuals such as women living with HIV. There is a need to generate data on the impact of HIV infection in pregnancy on maternal and infant immunity to vaccines against pertussis. Methods: This is a phase II, randomized controlled observer blind clinical trial of 100 women living with HIV and 100 uninfected women randomized to either standard vaccines (tetanus diphtheria vaccine, Td) or a tetanus diphtheria-pertussis vaccine (Tdap). Participants aged 18-40 years carrying a low-risk singleton pregnancy with a gestational age between 16 and 26 weeks confirmed on ultrasound scan, with no history of receipt of tetanus or pertussis vaccines in the current pregnancy will be recruited. Women will receive either two doses of Td or a first dose of Td and second dose of Tdap vaccine. Participants will complete 14-day diary cards to monitor reactogenicity. Mother-infant dyads will be followed up until the infant is one year old. The outcomes include: safety for the pregnant woman and infant; anti-pertussis toxin (PT) and anti-filamentous haemagglutinin (FHA) IgG concentrations in maternal, cord and infant blood and breastmilk, compared by maternal HIV status. Discussion: This study will investigate whether vaccines given to women living with HIV have similar immunogenicity and reactogenicity to vaccines given to pregnant women without HIV and monitor the effect of Tdap in pregnancy on infant immune responses. clinicalTrials.gov registration: NCT04589312 (19/10/2020)

Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial.

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.

Can telerehabilitation services combined with caregiver-mediated exercises improve early supported discharge services poststroke? A study protocol for a multicentre, observer-blinded, randomized controlled trial

BackgroundRecovery of walking ability is an important goal for patients poststroke, and a basic level of mobility is critical for an early discharge home. Caregiver-mediated exercises could be a resource-efficient strategy to augment exercise therapy and improve mobility in the first months poststroke. A combination of telerehabilitation and face-to-face support, blended care, may empower patient-caregiver dyads and smoothen the transition from professional support to self-management. The Armed4Stroke study aims to investigate the effects of a caregiver-mediated exercise program using a blended care approach in addition to usual care, on recovery of mobility in the first 6 months poststroke.MethodsA multicentre, observer-blinded randomized clinical trial in which 74 patient-caregiver dyads will be enrolled in the first 3 months poststroke. Dyads are randomly allocated to a caregiver-mediated exercises intervention or to a control group. The primary endpoint is the self-reported mobility domain of the Stroke Impact Scale. Secondary endpoints include care transition preparedness and psychological functioning of dyads, length of inpatient stay, gait-related measures and extended ADL of patients, and caregiver burden. Outcomes are assessed at enrolment, end of treatment and 6 months follow-up.ResultsDuring 8 weeks, caregivers are trained to become an exercise coach using a blended care approach. Dyads will receive a tailor-made, progressive training program containing task-specific exercises focusing on gait, balance, physical activity and outdoor activities. Dyads are asked to perform the training program a minimum of 5 times a week for 30 min per session, supported by a web-based telerehabilitation system with instruction videos and a messaging environment to communicate with their physiotherapist.ConclusionsWe hypothesize that the Armed4Stroke program will increase self-reported mobility and independence in ADL, facilitating an early discharge poststroke. In addition, we hypothesize that active involvement of caregivers and providing support using blended care, will improve the care transition when professional support tapers off. Therefore, the Armed4Stroke program may complement early supported discharge services.Trial registrationNetherlands Trial Register, NL7422. Registered 11 December 2018.

Comparison of a new gasless method and the conventional CO2 pneumoperitoneum method in laparoendoscopic single-site cholecystectomy: a prospective randomized clinical trial

To avoid CO2 pneumoperitoneum-associated cardiopulmonary side-effects during conventional laparoscopic surgeries, we have developed a gasless laparoscopic operation field formation (LOFF) device for laparoendoscopic single-site surgery. The aim of this study is to analyze the safety and efficacy of the LOFF device for laparoendoscopic single-site cholecystectomy and to verify its advantage of avoiding CO2 pneumoperitoneum-associated complications. In this prospective, randomized, observer-blinded clinical trial, eligible participants were randomized in a 1:1 ratio to undergo either conventional CO2 pneumoperitoneum assisted laparoendoscopic single-site cholecystectomy (LESS) or the new gasless LOFF device assisted laparoendoscopic single-site cholecystectomy (LOFF-LESS). Outcomes including intra-operative respiratory and hemodynamic parameters, operation time, conversion rate, complication rate, et al were compared between the two groups. A total of 100 patients were randomized to the LESS group [n = 50; mean (SD) age, 49.5 (13.9) years; 24 (48.0%) women] and the LOFF-LESS group [n = 50, mean (SD) age, 47.4 (13.3) years; 27 (54.0%) women]. Compared with the LOFF-LESS group, the LESS group witnessed significant fluctuations in intra-operative respiratory and hemodynamic parameters. The tracheal extubation time of the LESS group was significantly longer (P = 0.001). The gasless LOFF device is safe and feasible for simple laparoscopic cholecystectomy and has a predominance of avoiding CO2 pneumoperitoneum-associated cardiopulmonary side-effects. Trial registration number: ChiCTR2000033702Graphic abstract

Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial

ObjectiveTo evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis.DesignInvestigator initiated, randomised, open label,...

Efficacy And Safety Of Travoprost Versus Timolol To Treat Early-Onset Ocular Hypertension Secondary To Vitrectomy: A Randomized Trial.

PurposeTo evaluate the efficacy and safety of travoprost 0.004% versus timolol 0.5% as an initial intraocular pressure (IOP)-lowering medication for ocular hypertension secondary to vitrectomy.Patients and methodsWe performed a randomized, controlled, observer-blinded clinical trial in the Eye & ENT Hospital of Fudan University in China. This trial was registered at www.chictr.org.cn (ChICTR1800014942) before patient enrollment. Seventy-nine adults with IOP of 25–45 mmHg secondary to vitrectomy in the latest one month were enrolled and randomized to receive travoprost 0.004% or timolol 0.5%. More drugs were administered to patients with IOP > 25 mmHg during follow-up.ResultsThe mean IOP reduction at day 1 was −10.97 mmHg in the timolol group and −15.02 mmHg in the travoprost group (P = 0.006); no significant difference was observed between the groups at later time points. The number of IOP-lowering medications at day 21 was 0.64 in the timolol group and 1.15 in the travoprost group (P = 0.038), while no significant differences were observed at other time points. The proportion of single IOP-lowering medications used during the 4-week follow-up was 72.73% in the timolol group and 68.42% in the travoprost group (P = 0.692). Inflammation scores were not significantly different in the two groups at any time point. Increased ocular hyperemia occurred in 8 patients (19%) in the travoprost group and none in the timolol group (P = 0.005). There were no significant differences in other adverse events between the two groups. After logistic regression model analysis, IOP ≥ 30 mmHg, inflammation score ≥ 2, and silicone oil as tamponade were found to be the factors with significant effects on the number of IOP-lowering medications used during the 4-week follow-up.ConclusionTravoprost and timolol have similar efficacy and safety for treating ocular hypertension secondary to vitrectomy.

The role of oral simethicone on the adenoma detection rate and other quality indicators of screening colonoscopy: a randomized, controlled, observer-blinded clinical trial

Combining simethicone (SIM) with a colon preparation agent has been shown to improve mucosal visibility during screening colonoscopy, but its effect on the adenoma detection rate (ADR) remains unclear. SIM is commonly used through the endoscope to eliminate bubbles during endoscopy. However, this practice recently has been associated with endoscope-transmitted infections. Our aims were to determine the role of SIM added to a polyethylene glycol preparation on the ADR, procedure times, colon preparation, and intraprocedural use of SIM. This was a randomized, controlled, observer-blinded, clinical trial of patients undergoing screening colonoscopy. Patients with a high risk of colorectal cancer were excluded. Patients were randomly assigned to 2 different preparations: polyethylene glycol plus SIM or polyethylene glycol. Two endoscopists blinded to patient preparation regimens scored its quality by using the Boston Bowel Preparation scale (BBPS) and the bubble scale. Interobserver agreement was calculated. The polyp detection rate, ADR, intraprocedural use of SIM, cecal intubation time, and withdrawal time were recorded. For study purposes, cecal intubation time and withdrawal time were combined to determine the effective procedure time. No significant difference between the polyethylene glycol plus SIM and polyethylene glycol arms was seen regarding the ADR (33.3% vs 38.8%; P= .881) and effective procedure time (759.3 ± 253.1 seconds vs 800.2 ± 459.6 seconds; P= .373), respectively. Intraprocedural use of SIM as well as the bubble scale score were significantly lower in the polyethylene glycol plus SIM arm (1.6% vs 48.9%; P≤ .05) and (0.1 vs 2.1; P≤.05), respectively. Conversely, no difference was found in the BBPS scores. The interobserver agreement for both scores was strong (bubble scale score kappa= .537; P< .05; BBPS score kappa= .184; P<.05). Adding SIM to a polyethylene glycol preparation did not improve the ADR or effective procedure time. Nevertheless, it resulted in lower bubble scale scores, and more importantly, in less intraprocedural use of SIM. This simple and inexpensive intervention may have the potential to reduce the risk of endoscope-transmitted infections. (Clinical trial registration number: NCT03119168.).

Efficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for colonoscopy (Clensia): a multicenter randomized observer-blind clinical trial vs. a low-volume PEG with ascorbic acid (PEG-ASC).

Background and study aims Quality of inspection during colonoscopy is strictly related to the level of cleansing. High-volume (PEG-based) solutions are highly effective and safe, but their high volume affects tolerability and compliance. The aim of this study was to compare a new low-volume PEG with citrate and simethicone solution (PMF 104,Clensia) with a low-volume PEG with ascorbic acid solution (PEG-ASC; Moviprep). Patients and methods This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF 104 and PEG-ASC. In both groups, patients were instructed to take a full-dose regimen the evening before if colonoscopy was scheduled before 11 am to 12 pm, or to take a split regimen if colonoscopy was scheduled after 11 am to 12 pm. The primary end-point was an equivalence between PMF104 and PEG-ASC in the rate of adequate level of cleansing (Ottawa scale ≤ 6), with safety, mucosal visibility, tolerability, acceptance and compliance being also assessed. Results Of the 403 enrolled, 367 patients (Mean age [SD]: 55.6 (14.4) years; male:166 [45.2 %]) were included in the per protocol (PP) analysis: 184 being randomized in the PMF 104 group and 183 in the PEG-ASC group. Successful bowel cleansing was 78.3 % and 74.3 % in PMF104 and in PEG-ASC, respectively ( P = 0.37). Both preparations were equally safe (mild adverse events were observed in 9.2 % and 9.3 % of patients in the PMF104 and in the PEG-ASC group, respectively) and acceptable (no or mild distress during the intake in 81.4 % and 80.8 % in the PMF104 in the PEG-ASC, respectively [ P = 0.74]). Conclusion The new low-volume product Clensia is equivalent to the reference low-volume PEG-ASC in terms of bowel cleansing, safety and acceptance.

PG - 04: Hemi Diaphragmatic Function Assessment Following Ultrasound Guided Supraclavicular Versus Costoclavicular Brachial Plexus Block-A Randomized Observer Blinded Clinical Trial

PG - 04: Hemi Diaphragmatic Function Assessment Following Ultrasound Guided Supraclavicular Versus Costoclavicular Brachial Plexus Block-A Randomized Observer Blinded Clinical Trial

Long-term outcome of highly myopic foveoschisis treated by vitrectomy with or without gas tamponade.

To evaluate the long-term safety and efficacy of vitrectomy and internal limiting membrane (ILM) peeling with or without gas tamponade for highly myopic foveoschisis. We performed an open-label, observer-blinded clinical trial of 85 patients with myopic foveoschisis between 2000 and 2012. Patients were randomly allocated to one of two groups, those who received vitrectomy and ILM peeling without gas tamponade (no-gas group) or those who with gas tamponade (gas group) and follow up at least 5y. Visual acuity of gas group improved from 0.82±0.33 to 0.79±0.73 in 6mo, improved to 0.71±0.67 in 1y and within this range in the following 4y. Visual acuity of no-gas group improved from 0.81±0.46 to 0.78±0.66 in 6mo, improved to 0.70±0.65 in 1y. The finial visual acuity of two groups were significantly increased compared with the baseline (P<0.05). The visual acuity was improved in 35 of 40 eyes (87.5%) in gas group and 29 of 33 eyes (87.9%) in no-gas group, while there were no significant differences between gas group and no-gas group in the visual acuity. The foveoschisis on optical coherence tomography (OCT) completely resolved in 5 of 40 eyes in 1mo, 14 eyes in 6mo and 40 eyes in 1y in the gas group. While the foveoschisis completely resolved in 4 of 33 eyes in 1mo, 10 eyes in 6mo and 33 eyes in 1y in the no-gas group. Vitrectomy and ILM peeling without gas tamponade appears to be as effective in the treatment of myopic foveoschisis as vitrectomy and ILM with gas tamponade. However, eyes treated with no-gas tamponade showed more rapid resolution of myopic foveoschisis.

Lack of a clear disease modifying activity of celecoxib in treatment of end-stage knee osteoarthritis: a rondomized observer blinded clinical trial

Lack of a clear disease modifying activity of celecoxib in treatment of end-stage knee osteoarthritis: a rondomized observer blinded clinical trial

The ONLINE-TICS Study Protocol: A Randomized Observer-Blind Clinical Trial to Demonstrate the Efficacy and Safety of Internet-Delivered Behavioral Treatment for Adults with Chronic Tic Disorders.

In recent years, behavioral therapy with comprehensive behavioral intervention for tics (CBIT) has been recognized as an effective and safe treatment in patients with Gilles de la Tourette syndrome. In Germany, however, dissemination of CBIT is restricted due to a considerable lack of well-trained therapists. The aim of this study is to overcome this deficiency by creating a new and sophisticated Internet-delivered CBIT (iCBIT) program. With this study, we want to demonstrate that iCBIT is superior to Internet-delivered psychoeducation and comparable to face-to-face CBIT. This is a multicenter, prospective, randomized, controlled, observer-blind clinical trial, which will be conducted at five sites in Germany (ONLINE-TICS). Over the course of 2 years, 160 adult patients with chronic tic disorders will be assigned to one of three treatment arms: iCBIT (n = 72), online psychoeducation (n = 72), or face-to-face CBIT (n = 16). All treatments will consist of eighty therapy sessions over a period of 10 weeks and will follow the well-established CBIT manual by Woods and colleagues. The primary outcome measure will be the change in Yale Global Tic Severity Scale (YGTSS) at 1-week posttreatment. Secondary outcome measures include YGTSS change at 3 and 6 months, video- and self-ratings of tics as well as scales for psychiatric comorbidities assessed at each visit. The primary analysis will compare iCBIT to online psychoeducation using a mixed linear model with the YGTSS change as dependent variable. Secondary analyses will look at the comparison between iCBIT and face-to-face CBIT in a non-inferiority analysis. If iCBIT proves to be effective, it would be a considerable contribution to close the wide gap in treatment providers for tic disorders not only in Germany but also in several other countries, since this Internet-delivered therapy does not require the supervision of a therapist. In addition, iCBIT would be a cost-effective and readily available treatment alternative that guarantees high quality standard of CBIT. All institutional review boards approve the protocol. All participants will provide informed consent. There are no conflicts of interest. After study completion, the results will be published. ClinicalTrials.gov Identifier: NCT02413216.

Tracheal intubation with volatile induction and target bispectral index of 25 versus 40: A randomized clinical trial.

Background and Aims:A target bispectral index (BIS) value of 40 is considered adequate for depth of anesthesia, but no consensus exists regarding BIS value for tracheal intubation without neuromuscular blocking drugs. The aim of this randomized, double-blinded study was to compare the total duration from sevoflurane induction to tracheal intubation at a BIS value of 25 or 40.Material and Methods:This study was a prospective, randomized and observer-blinded clinical trial. After approval of the Institutional Ethics Committee and written informed consent, 80 patients of American Society of Anesthesiologists physical status I-II, aged 20-60 years, of either sex, requiring general anesthesia with tracheal intubation were enrolled. The patients were randomized to either Group BIS40-intubation at a target BIS value of 40 ± 5 or group BIS25-intubation at a target BIS value of 25 ± 5. The intubating conditions, hemodynamic, and adverse effects were observed in both the groups.Results:This study showed that the total time required from induction to tracheal intubation was 4.9 ± 0.9 min in group BIS40 as compared to 6.3 ± 0.5 min in group BIS25 (P = 0.001) using two-tailed sample t-test. The mean intubation score was 6.5 ± 0.9 in group BIS40, and 5.1 ± 0.7 in group BIS25 (P = 0.001) using Mann-Whitney U-test.Conclusion:The time to achieve target BIS value of 25 was greater as compared to target BIS value of 40 during sevoflurane induction but provided better intubating conditions in the absence of neuromuscular agents.

Study of pentoxifylline effects on motility and viability of spermatozoa from infertile asthenozoospermic males.

Background:The quality of semen is one of the major parameters in male infertility. Pentoxifylline, a methylxanthine derivative, is an agent primarily used in the treatment of intermittent claudication and other vascular disorders. Studies have shown that pentoxifylline enhances the quality and quantity of sperms. In this study, we have investigated the in vitro effects of pentoxifylline on viability and motility of spermatozoa in samples of infertile oligoasthenozoospermic males.Materials and Methods:In this observer-blinded clinical trial, semen samples of 25 infertile oligoasthenozoospermic males were collected in Alzahra Educational Medical Center of Tabriz University of Medical Sciences from August 2010 to August 2012. After the isolation of spermatozoa by the swim-up method, they were randomized into four groups in ISM1 environment: The controls treated normally: Group 1 treated by pentoxifylline at a dose of 50 μg/ml, Group 2 treated by pentoxifylline at a dose of 100 μg/ml, and Group 3 treated by pentoxifylline at a dose of 200 μg/ml. Sperm viability and motility were compared among the groups on 45 min, 24 h, 36 h, and 48 h intervals.Results:Mean percentages of live sperms were 98.40%, 51.40%, 20.60%, and 6.00% in control group and 98.40%, 69.20%, 38.60%, and 14.60% in Group 3 on the mentioned intervals, respectively. This mean percentage decrease of live sperms was significantly lower in Group 3 comparing with that of other groups (P = 0.01). Mean percentages of motile sperms were 54%, 8.40%, 2.80%, and 0% in control group; and 54%, 16%, 4.80%, and 1.40% in Group 3 on the mentioned intervals, respectively. There was not a significant difference between the four groups in this regard (P = 0.19).Conclusion:Pentoxifylline can enhance the viability of sperm of infertile oligoasthenozoospermic males with no significant effect on its motility.

Effects of high-intensity aerobic exercise on psychotic symptoms and neurocognition in outpatients with schizophrenia: study protocol for a randomized controlled trial.

BackgroundThe focus in recent years on physical inactivity and metabolic disturbances in individuals with schizophrenia raises the question of potential effects of physical activity. Physical activity has shown beneficial effects on cognition in healthy older individuals as well as on symptom severity in depression. However, opinions diverge regarding whether aerobic high-intensity interval training reduces cognition and key symptoms in schizophrenia. The main objective for the trial is to investigate the potential effects of aerobic high-intensity interval training on neurocognitive function and mental symptoms in outpatients with schizophrenia.Methods/DesignThe trial is designed as a randomized controlled, observer-blinded clinical trial. Patients are randomized to 1 of 2 treatment arms with 12-week duration: aerobic high-intensity interval training or computer gaming skills training. All participants also receive treatment as usual. Primary outcome measure is neurocognitive function. Secondary outcome measures will be positive and negative symptoms, wellbeing, tobacco-smoking patterns and physiological/metabolic parameters. Patient recruitment takes place in catchment area-based outpatient clinics.Trial registrationClinicalTrials.gov NCT02205684. Registered 29 July 2014.

Effectiveness of cold therapy in reducing pain, trismus, and oedema after impacted mandibular third molar surgery: a randomized, self-controlled, observer-blind, split-mouth clinical trial

Cold therapy is a conventional and widely used modality for reducing pain, trismus, and oedema after dentoalveolar surgeries. However, information reported in the literature on its effectiveness is insufficient and controversial. This study was performed to evaluate the effect of local cold application in reducing pain, trismus, and swelling after impacted mandibular third molar surgery. Thirty patients (seven males and 23 females) with bilateral symmetrical mandibular impacted third molars were enrolled in this randomized, self-controlled, observer-blind clinical trial. The patients were aged between 18 and 30 years. After surgical removal of the tooth on one side (intervention), ice pack therapy was given for 24h after surgery; for the other side (control), no cold therapy was given. The time interval between the two surgeries was at least 4 weeks. The amount of pain, trismus, and facial swelling was measured on days 2 and 7 postoperative, and patient satisfaction with the cold therapy vs. no cold therapy was assessed. The amount of pain, trismus, and facial swelling, and the extent of patient satisfaction were not significantly different between the intervention and control sides. Cold therapy had no beneficial effects on postoperative sequelae after impacted mandibular third molar surgery.

Comparison of the Intraoperative Outcomes of Intrauterine Instillation of Epsilon-Aminocaproic Acid and Intravenous Oxytocin in Hysteroscopy Surgeries

Objectives:As the technique of choice, hysteroscopy can be used in visualizing and treating intrauterine pathologies such as polyps, septa, fibroids and endometrial hyperplasia. The best visualization, however, is attained when the endometrium is flat or atrophic; or a pre-existing active bleeding is minimal or suspended during hysteroscopy. Both epsilon-aminocaproic acid (EACA) and oxytocin have been found effective against active bleeding. The present work aimed to compare the efficacy and safety of intrauterine EACA and intravenous oxytocin in the management of intractable uterine bleeding in candidates of operative hysteroscopy. Materials and Methods:In this single-center, observer-blinded clinical trial, 144 candidates of operative hysteroscopy with intractable moderate uterine bleeding were randomized in two groups, receiving either intrauterine instillation of EACA (2 g in 1 L of 5% dextrose serum, n = 72) or intravenous oxytocin (10 IU/L, n = 72). The operator graded the severity of intraoperational bleeding (I = no to V = most severe). Serum hematocrit and hemoglobin changes, intra- and post-operational complications, the mean operative time, and the mean volume of the employed media were also recorded and compared between the two groups. Results: The two groups were comparable in terms of age, gravidity and parity. Grades I, II and III of intraoperational bleeding were reported in 79.2%, 18.1% and 2.8% of cases in the EACA group, and 18.2%, 65.3% and 16.7% of the cases in the oxytocin group, respectively (P < 0.001). While the two groups were also comparable in terms of serum hematocrit and hemoglobin changes, intra- and post-operation complications (none in both groups) and the mean volume of the media intraoperatively, the mean operative time was significantly shorter in patients who received intrauterine instillation of EACA (10.28 ± 3.24 minutes vs. 11.81 ± 4.62 minutes, P = 0.02). Conclusion:Owing to less severe intraoperative hemorrhage and shorter duration of operation in the group who received intrauterine instillation of EACA than those with intravenous injection of oxytocin, we recommend the intrauterine EACA in managing intractable uterine bleeding in candidates of hysteroscopy.

Testing The Intranasal Route For Administration of Haloperidol In Emergency Room: Generation of Efficacy Data To Support Clinical Practice

TeSTiNg The iNTraNaSal rouTe For admiNiSTraTioN oF haloperidol iN emergeNCy room: geNeraTioN oF eFFiCaCy daTa To SupporT CliNiCal praCTiCe R. Vives Vilagut; R. Duno; N. Planet; G. Garcia; M. Payes; M. Marinosa; M.I. Iglesias-Lepine; and C. Pontes Hospital de Sabadell. Institut Universitari Parc TauliUniversitat Autonoma de Barcelona Background: Managing schizophrenic patients with agitation in the emergency room requires medications with a rapid onset of effect. Intravenous administration is impractical, and intramuscular dosing may be risky for both patients and health care professionals. The intranasal route may offer short Tmax with safer administration. Intranasal haloperidol has been reported to achieve similar plasma concentrations to intravenous dosing, but clinical data on the efficacy and safety of such approach is lacking. Psychiatrists contacted our Clinical Pharmacology Unit for methodological and logistic support to generate clinical information on the affectivity of haloperidol by the intranasal route. We present here the research protocol that was prepared. Methods: An exploratory randomized parallel observer-blinded clinical trial was designed to compare the administration of 5mg haloperidol by either intranasal or intramuscular route. The trial will include 40 agitated schizophrenic patients visited in the emergency room of Corporacio Parc Tauli who are candidates to receive haloperidol and provide previous informed consent (personally or through representative). Patients will be monitored up to 6 hours for agitation, cardiovascular parameters and adverse events. Treatments will be administered by unblinded nurses and agitation will be assessed in blind by an uninvolved psychiatrist. Main efficacy variable is the percentage of patients with score ≤ 9 in the 5 item PANSS-EC scale 20 minutes after dosing. Sample size is based on subject’s availability considering the exploratory nature of the trial. The study will be performed according to the Good Clinical Practice. Results: The clinical trial obtained Ethic’s and regulatory approvals during 2014. The first patient was recruited on December 2014. Recruitment is ongoing and expected to last 12 months. Conclusions: An exploratory trial has been prepared to help physicians to generate initial clinical information on the effectiveness of a simple intervention aimed to improve patient management by healthcare professionals in the emergency room.