Double-arm Study Research Articles

Effectiveness and safety of Ciclopirox Olamine compared to that of Luliconazole in management of patients with multi-site dermatophytosis on background itraconazole therapy

Wide spread, inappropriate use of antifungal drugs in dermatophytosis has resulted in rise in minimum inhibitory concentration (MIC) values and reduced response. Hence there is a need for a different antifungal with a novel mechanism of action.This was an open-label, randomised, prospective, interventional, comparative, double-arm study. The patients were treated with either topical ciclopirox olamine or luliconazole twice daily for 6 weeks. All the patients were taking oral itraconazole 100mg twice daily for 4 weeks. Effectiveness endpoints were percentage of patients achieving complete cure, clinical cure and mycological cure at the end of the treatment period from baseline. Safety was assessed by analyzing the AEs and monitoring of liver function tests. 92 patients were included in the study. 44 and 43 patients completed the study in ciclopirox and luliconazole group respectively. 84.09%, 88.63% and 86.36% patients achieved ccomplete, clinical and mycological cure rate in ciclopirox group respectively. 83.72%, 88.37% and 86.04% patients achieved complete, clinical and mycological in luliconazole group respectively. 10.63% patients in the Ciclopirox group and 10.86% in the Luliconazole group reported one or more drug related AE. Nausea, skin rash, head ache and vomiting were AEs reported. The results of this study prove that Ciclopirox is novel antifungal agent which is efficacious and safe in the management of dermatophytosis.

The impact of nasal surgery on sleep quality

ObjectiveNasal obstruction is considered to be one of the risk factors for obstructive sleep apnea, together with a high arched narrow palate, elongated uvula, malocclusion, and tongue and tonsil size. The impact of nasal obstruction on sleep apnea is controversial, however, and its relation to sleep quality is rarely discussed. The purpose of this study was to investigate the independent effect of nasal obstruction on sleep quality. MethodsSixty-nine patients with nasal obstructive symptoms and without sleep apnea episodes were enrolled from September 2018 to August 2019, and compared before and after surgery with thirty-four patients who had benign diseases of the thyroid or parathyroid as a control group, to investigate effects of surgery. Sleep quality was evaluated using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J). All cases were reassessed at three months after surgery. ResultsThe postoperative PSQI scores in the nasal surgery group were significantly lower than the preoperative scores (p < 0.001). In contrast, there was no statistically significance difference between the pre- and postoperative PSQI scores in the neck surgery group. Difference of PSQI scores before and after surgery in the nasal surgery group was significantly higher than the neck surgery group. ConclusionsThis double-arm study suggests that reduction of nasal disfunction with nasal surgery contributes significantly to sleep quality, in patients who may not have noticed their impaired quality of sleep previously because of their long-term nasal symptoms.

Effect of Virechana Karma along with Guggulu Kalpanas in the management of Medoroga - A Double Arm Study

Metabolism is the natural process of the body, which is necessary to maintenance of the homeostasis of an individual person. Everybody constitutions are always in the process of metabolism, which is a combination of Anabolism (Construction) and Catabolism (Deterioration). As Agni is prime factor for all the Chayapachayakriya. Medoroga, is one of the Metabolic disease, in which contributing factors are Agni, Ama along with Kaphapradhana Tridosha, Medodhathu. Due to various types of etiological factors, the Agni in the body gets vitiated and Jatharagnimandya occurs. By this Jatharagnimandya, Dhathuparinama will not occur properly. This will lead to Medoroga and further many other Upadravas. To correct these conditions, Ayurveda has many modes of therapies like Samshodhana, Samshamana. By these we can correct the metabolism from the root cause. Here 40 Subjects diagnosed with Medoroga w.s.r. to Hyperlipidemia fulfilling the Inclusion criteria were selected for study and randomly categorized into two groups as Group A and Group B each consisting of 20 subjects. For both groups Amapachana with Chitrakadi Vati, Sadhyosnehapana with Murchita Sarshapa Taila, Sarvanga Abhyanga with Murchita Tila Taila followed by Swedana. And Virechana was administered with Virechana Gulika. Than each group received two different Shamanoushadhi. So, the objective of the study is to establish the efficacy of Virechana along with Dashanga Guggulu and Virechana along with Shadushana Guggulu in the management of Medoroga.

Role of tranexamic acid in axillary lymph node dissection in breast cancer patients.

Axillary lymph node dissection (ALND) is an important step in the management of node-positive operable breast cancer. It is associated with large amount of axillary drainage and increased risk of wound-related infection. Tranexamic acid (TA) has antifibrinolytic property and is being extensively used in controlling blood loss. However, its role in reducing axillary drainage after ALND is still not well-established. The aim of this study is to evaluate the effectiveness of TA in reducing the axillary drainage, early removal of the drain, and decreasing the wound-related infection in breast cancer patients undergoing ALND. This is a prospective nonrandomized double-armed cohort study. Total of 47 patients were included in the TA group and 46 in the nontranexamic (NTA) group. All the patients in TA group received a single dose of intravenous (IV) TA at the time of induction followed by oral TA for five days after surgery. Both TA and NTA groups had similar proportions of locally advanced breast cancers (57.4% vs 56.5%, P=.90). Majority of them underwent modified radical mastectomy (MRM) (70.2% vs 67.4%, P=.76). Patients in TA group had significantly lower axillary drainage (440ml vs 715.5ml, P=.003) with earlier removal of the drain (8 vs 11days, P=.046). Seroma formation (19.1% vs 32.6%, P=.13) and wound-related infection (4.3% vs 8.7%, P=.43) were nonsignificantly lower in the TA group. Tranexamic acid reduces axillary drainage and facilitates early removal of the drain after axillary lymph node dissection.

An open-label, prospective, comparative, double-arm clinical trial to evaluate the safety and effectiveness of minocycline extended-release formulation compared with minocycline immediate-release formulation in the management of patients with papulopustular acne

Introduction: Minocycline because of its multiple advantages is considered as first-line therapy in the management of acne. However, conventional formulations of minocycline are associated with multiple side effects, thus limiting its use. Thus, extended-release formulation of minocycline was developed. Materials and Methods: This was an open-label, prospective, interventional, comparative, double-arm study. Patients with papulopustular acne were either received minocycline extended release (ER) 1 mg/kg/day or minocycline immediate release (IR) 100 mg/day for a period of 8 weeks. Safety was assessed by analyzing the adverse event (AE) profile in both the groups. Effectiveness was assessed by analyzing improvement in the mean inflammatory lesion count. Results: A total of 100 patients were included in the study, 50 in each group. A total of four AEs were reported by 2 (4.0%) patients in the ER group, whereas ten AEs were reported by 5 (10.0%) patients in the IR group. The mean inflammatory lesion count in the ER group at baseline was 14.95 ± 3.76, whereas in the IR group, it was 14.52 ± 3.38. Significant decrease in inflammatory lesion count was observed in both the groups during treatment period. Conclusion: The results of this study prove that ER formulation of minocycline is associated with better improvement in acne compared to IR formulation. The study also proves that ER formulation is associated with better safety profile compared to IR profile.

Ablation outcomes of low versus high doses of radioiodine (131I) in patients with differentiated thyroid carcinoma following thyroidectomy

Objective The aim was to compare the ablative efficacy of low vs high doses of radioactive iodine-131 (131I) in patients with differentiated thyroid carcinoma (DTC) after total or near total thyroidectomy. Materials and methods A randomized, double-armed clinical study compared the ablation outcomes of patients with low and intermediate risk DTC after administration of low (30 mCi) vs high doses (80–120 mCi) of 131I for 20 and 25 patients, respectively. All the included patients were re-examined under thyroid-stimulating hormone stimulation 6–8 months after 131I administration. Successful ablation is defined as follows: Absence of any significant 131I uptake at the thyroid bed or abnormal uptake elsewhere in the body in the diagnostic whole-body scan, stimulated serum thyroglobulin less than 2 ng/ml with negative antithyroglobulin antibodies, and free neck ultrasonography (no thyroid residue or pathological cervical lymph nodes). Results Overall successful ablation after a single dose of 131I was reported in 34/45 patients representing 75.6% of the whole patient population, while unsuccessful ablation was reported in the remaining 11 (24.4%) patients. Successful ablation was reported in 15 out of 20 patients (75%) in the low-dose group and in 19 out of 25 cases in the high-dose group (76%) (P=1.000). Conclusion Ablation with low-dose radioactive iodine (30 mCi) in patients with DTC who did not have gross residual disease or cervical lymphadenopathy after surgical treatment is as effective as the high one (80–120 mCi).

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection. This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities.

Laparoscopic and Robotic Hysterectomy in Endometrial Cancer Patients with Obesity: A Systematic Review and Meta-Analysis of Conversions and Complications

Study Objective Robotic assistance may facilitate completion of minimally invasive hysterectomy, which is the standard of care for the treatment of early-stage endometrial cancer, in patients for whom conventional laparoscopy is challenging. The aim of this systematic review was to assess conversion to laparotomy and perioperative complications after laparoscopic (LH) and robotic hysterectomy (RH) in endometrial cancer patients with obesity. Design We systematically searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews (January 1, 2000 to July 18, 2018) for studies of endometrial cancer patients with obesity (body mass index, BMI≥30 kg/m2) undergoing primary hysterectomy. We generated pooled proportions of conversion, organ/vessel injury, venous thromboembolism (VTE), and blood transfusion. We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Scale for double-arm studies. Setting N/A Patients or Participants N/A Interventions N/A Measurements and Main Results We identified 51 observational studies reporting on 10,800 endometrial cancer patients with obesity (study-level BMI: 31.0-56.3). The pooled proportions of conversion from LH and RH were 6.5% (95% CI 4.3-9.9) and 5.5% (3.3-9.1) respectively among patients with BMI≥30, and 7.0% (3.2-14.5) and 3.8% (1.4-9.9) among patients with BMI≥40. Inadequate exposure due to adhesions/visceral adiposity was the most common reason for conversion for both LH (32%) and RH (61%); however, intolerance of Trendelenburg caused 31% of LH conversions and 6% of RH conversions. The pooled proportions of organ/vessel injury (LH 3.5% [2.2-5.5]; RH 1.2% [0.4-3.4]), VTE (LH 0.5% [0.2-1.2]; RH 0.5% [0.1-2.0]), and blood transfusion (LH 2.8% [1.5-5.1]; RH 2.1% [1.6-3.8]) were low and not appreciably different between arms. Conclusion RH and LH have similar rates of perioperative complications in endometrial cancer patients with obesity, but RH reduces conversions due to positional intolerance in patients with morbid obesity. Existing literature is limited by selection and confounding bias, and randomized trials are needed to inform practice standards in this population.

1185PD - Parallel comparison of 4-1BB or CD28 co-stimulated CD19-targeted chimeric antigen receptor-T cells for B-cell non-Hodgkin lymphoma

BackgroundCD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin lymphoma (B-NHL). However, studies comparing the clinical outcomes of 28z CAR-T versus BBz CAR-T are lacking. Analysis of our previous double-arm clinical study of 28z CAR-T and BBz CAR-T in treatment of r/r B-ALL (18 cases for each arm) revealed that BBz CAR-T showed shorter initial response time, higher tumor-killing capacity, higher overall survival rate, longer persistence, and less severe cytokine release syndrome and neurotoxicity than 28z CAR-T. This study investigated the efficacy and toxicity of both CAR-T types in B-NHL patients. MethodsBBz CAR-T and 28z CAR-T were prepared under identical manufacturing processes. Patients with r/r B-NHL were pre-treated with fludarabine and cyclophosphamide, and infused with 28z or BBz CAR-T. Tumor burden, CAR-T persistence and adverse events were monitored. The CAR-T that induced dose-limiting toxicity in less than one patient was further evaluated based on dose escalation. ResultsSix patients were treated at the dose of 0.75-5×105/kg. Both types of CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within three months. Cytokines including interleukin (IL)-6 and IL-10 were increased after CAR-T infusion. The peak levels of IL-6 and IL-10 were much higher in the 28z CAR-T cohort. Severe cytokine release syndrome (CRS), CAR-T cell related encephalopathy syndrome (CRES) (≥ grade 3), and one death occurred in the 28z CAR-T cohort, resulting in the termination of recruitment of this cohort. Six more patients received BBz CAR-T cells at a dose of 1×106/kg with one-month CR rate of 83% and only grade 1/2 adverse events. ConclusionsBBz CAR-T showed similar antitumor activity, but a more favorable safety profile, compared with 28z CAR-T. This study proved the competence of BBz CAR-T in B-NHL therapy, at least under our manufacturing process. Legal entity responsible for the studyPeking University Cancer Hospital & Institute. FundingImmunochina Pharmaceuticals Co., Ltd. DisclosureAll authors have declared no conflicts of interest.

Oncologic outcomes and morbidity following heated intraperitoneal chemotherapy at cytoreductive surgery for primary epithelial ovarian cancer: A systematic review and meta-analysis.

e17093 Background: Heated intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery in the treatment of primary epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy was associated with a significant 12 months improved overall survival (OS) in a well-designed randomized controlled trial. Nonetheless, there remains uncertainty about the benefit and safety of HIPEC in ovarian cancer. The aim of this review was to assess efficacy and safety of HIPEC in primary EOC. Methods: We conducted a systematic search in Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to February 22nd 2018 for observational and randomized studies of patients with primary EOC undergoing HIPEC at cytoreductive surgery with no language restrictions . We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Quality Scale for double-arm studies. We determined the pooled proportion of 30-day grade 3-4 morbidity, reoperation, and postoperative death. Results: Thirty-five articles including 1937 patients with primary EOC met inclusion criteria. Timing of HIPEC and type of chemotherapy regimens were not consistent between studies. There was significant variation in the reported OS of patients treated with HIPEC at cytoreductive surgery for primary EOC (3-year OS:48-77%; 5-year OS:17-72%). Thirteen articles were including in a meta-analysis to determine to the safety of HIPEC. The pooled proportions for 30-day Grade 3-4 morbidity, 30-day reoperation, and 30-day postoperative death were 33.0% (95% CI 23.0-45.0), 9.0% (95% CI 5.0-17.0) and 3.0% (95% CI 1.0-5.0) respectively. Conclusions: The use of HIPEC in primary EOC is associated with significant morbidity. There is significant heterogeneity in current literature. Higher quality, large prospective randomized control trials are needed to further support the benefit of HIPEC at cytoreductive surgery in the first-line treatment of primary EOC.

Tel-eVax: a genetic vaccine targeting telomerase for treatment of canine lymphoma

Backgroundwe have recently shown that Tel-eVax, a genetic vaccine targeting dog telomerase (dTERT) and based on Adenovirus (Ad)/DNA Electro-Gene-Transfer (DNA–EGT) technology can induce strong immune response and increase overall survival (OS) of dogs affected by multicentric Diffuse Large B cell Lymphoma (DLBCL) when combined to COP therapy in a double-arm study. Here, we have utilized a clinically validated device for veterinary electroporation called Vet-ePorator™, based on Cliniporator™ technology currently utilized and approved in Europe for electrochemotherapy applications and adapted to electrogenetransfer (EGT).Methods17 dogs affected by DLBCL were vaccinated using two Ad vector injections (Prime phase) followed by DNA–EGT (Boost phase) by means of a Vet-ePorator™ device and treated in the same time with a 27-week Madison Wisconsin CHOP protocol. The immune response was measured by ELISA assays using pool of peptides.ResultsNo significant adverse effects were observed. The OS of vaccine/CHOP animals was 64.5 weeks, in line with the previous study. Dogs developed antibodies against the immunizing antigen.ConclusionsTel-eVax in combination with CHOP is safe and immunogenic in lymphoma canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. More importantly, our findings may translate to human clinical trials and represent new strategies for cancer treatment.

Clinical Outcomes of Successful Revascularization of Chronic Total Coronary Occlusions with Bioresorbable Vascular Scaffolds: A Systematic Review.

Revascularization of chronic total occlusions (CTO) with percutaneous coronary intervention is associated with favorable long-term clinical and echocardiographic outcomes. Whether bioresorbable vascular scaffolds (BVS) would be advantageous in the treatment of CTO is unknown as patients with these lesions were generally excluded from large BVS randomized trials. We performed a systematic review, which sought to summarize known data on mid- to long-term clinical outcomes for BVS in CTO. We searched MEDLINE, EMBASE, clinicaltrials.gov, and the Cochrane Library through April 2018 to look for studies on implantation of BVS in CTO. Outcomes of interest included myocardial infarction, cardiac death, all-cause mortality, major adverse cardiac events (MACE), vessel restenosis, scaffold thrombosis, and target lesion revascularization. A total of 13 articles met the inclusion criteria for analysis. All studies were observational with a total number of patients of 1,077. Only two studies included comparator groups which retrospectively compared BVS with drug-eluting stents (DES). The studies had variable size (21 to 537) and follow-up duration (3–23 months). The review showed favorable outcomes for BVS implantation in CTO with the reported incidence of MACE ranged from 0% to 6.7% with no significant differences between BVS and DES groups in double arm studies. Although data on the use of first-generation BVS in CTO are sporadic and limited by small sample observational studies, available evidence is promising and suggests of acceptable outcomes comparable with second generation DES. Further investigation with randomized clinical trials and use of newer generation scaffolds is required.

Hypophysitis Outcome and Factors Predicting Responsiveness to Glucocorticoid Therapy: A Prospective and Double-Arm Study.

Primary autoimmune hypophysitis (PAH) evolves in most untreated cases in irreversible hypopituitarism. PAH outcome, instead, after immunosuppressive treatment has not been completely clarified. To evaluate hypophysitis and pituitary function outcomes. A prospective, double-arm study with a 2-year follow-up. Referral center for pituitary disease. Twenty PAH cases. Oral prednisone 50 mg/d or conservative strategy by observation. Primary endpoint was the improvement/stabilization/worsening of PAH from baseline to a 2-year visit. Secondary endpoint was the improvement/stabilization/worsening of pituitary function from baseline to a 2-year visit. Twelve patients (57.1%) were treated with a glucocorticoid-immunosuppressive therapy, and eight patients (42.9%) were observed. At the 2-year visit, PAH improvement/recovery occurred in eight immunosuppressive-treated (66.7%) patients and in two untreated patients (25%). PAH worsened in three untreated patients (37.5%) and was considered stable in four immunosuppressive-treated (33.3%) and three untreated patients (37.5%). Improvement/recovery of pituitary function occurred more frequently in immunosuppressive-treated patients (58.3%) compared with untreated ones (25%; P = 0.04). Responsiveness to immunosuppressive treatment is correlated with antipituitary antibody presence (P = 0.01), occurrence of diabetes insipidus at PAH diagnosis (P = 0.01), absence of the physiological neuropituitary "bright spot" on T1-weighed images (P = 0.01), and pituitary stalk at optical chiasm larger than 3.9 mm (area under the curve: 0.97, sensibility: 100%, specificity: 100%; P = 0.04). On the other hand, we failed to identify factors predicting the outcome, among untreated patients. Glucocorticoid treatment of hypophysitis improves pituitary secretion and should be encouraged in accordance with the evaluation of endocrine-, immunological-, and morphological-predictive markers.

Clinical Outcomes of Treating Cervical Adjacent Segment Disease by Anterior Cervical Discectomy and Fusion Versus Total Disc Replacement: A Systematic Review and Meta-Analysis

Study Design:Systematic review and meta-analysis.Objective:To compare clinical outcomes of all available adjacent segment disease (ASD) cohorts being treated by either anterior cervical discectomy and fusion (ACDF) or total disc replacement (TDR).Methods:We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Searches of electronic databases from inception to August 2017 identified 349 articles for screening. Data was extracted and analyzed using meta-analysis of proportions.Results:The search identified 1 double-armed study and 8 single-armed studies from which data of 5 TDR and 5 ACDF cohorts treating ASD were extracted. Between the 2 pooled TDR (n = 103) and ACDF (n = 258) groups, baseline characteristics were predominantly similar. Compared with ACDF, TDR demonstrated superior operation duration (107 vs 188 minutes, P = .011) and range of motion of C2-C7 at final follow-up at least 1 year after surgery (40.2° vs 35.1°, P = .001). Other surgical and performance parameters including estimated blood loss, complications, and Japanese Orthopedic Association score, Neck Disability Index, Visual Analog Scale neck, and Visual Analog Scale upper limb measures were comparable between cohorts.Conclusion:TDR confers similar surgical and postoperative outcomes to the treatment of ASD as ACDF. Both procedures lead to improvement in all performance outcomes. Larger, prospective, randomized studies will validate the findings of this meta-analysis. Longer term studies are required to ascertain the recurrence rates of ASD following either surgical treatment of primary ASD.

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection

IntroductionIn Japan, prophylactic central node dissection (p-CND) for papillary thyroid carcinoma (PTC) has been routinely performed in many institutions, including ours (Kuma Hospital, Japan). We evaluated the recurrence to a central lymph node in patients with cN0M0 PTC who underwent routine p-CND.Materials and methodsWe enrolled 4301 patients with cN0M0 PTC who underwent an initial surgery between 1987 and 2005 (median age 51 years). The postoperative follow-up periods ranged from 4 to 362 months (median 164 months). Only 15 patients underwent radioactive iodine (RAI) ablation (≥30 mCi) after total or near total thyroidectomy.ResultsOf the 4301 patients with N0M0 PTC who underwent p-CND, 2548 (59%) were diagnosed as pN1a on postoperative pathological examination. To date, only 52 cases (1.2%) showed recurrence to a central lymph node. The 10-year and 20-year central node recurrence-free survival rates were excellent at 99.1 and 98.2%, respectively. On multivariate analysis, age ≥55 years, significant extrathyroid extension, tumor size >2 cm, and ≥5 pathologically confirmed central node metastases (but not the presence of central node metastasis) independently affected central node recurrence.ConclusionsUnder the situation of routine p-CND, the central node recurrence-free survival of cN0M0 PTC is excellent. However, future studies, including double-arm studies from Japan, should examine whether the omission of p-CND cN0M0 PTC is appropriate without RAI ablation in consideration of various factors, including the pros and cons of p-CND.

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial

BackgroundIntrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question.Methods/design‘The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine’ trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients.Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor’s accuracy for detecting respiratory depression.DiscussionThe trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety.Trial registrationClinicalTrials.gov, ID: NCT02885948. Registered retrospectively on 4 July 2016.Protocol Version 2.0, 3 April 2017.Protocol identification (code or reference number): UCDCRC/15/006EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

Variability of choroidal and retinal thicknesses in healthy eyes using swept-source optical coherence tomography - implications for designing clinical trials.

AimThe aim was to study the variability of choroidal scleral interface (CSI) thickness in healthy subjects and its relevance for designing future studies.MethodsA total of 123 volunteers were imaged using swept-source optical coherence tomography. Early treatment diabetic retinopathy grid was used.ResultsMean central retinal thickness was 285.85±14.53 µm and 287.18±12.93 µm, and mean central CSI thickness was 273.94±77.77 µm and 271.19±78.85 µm for the right and left eyes, respectively. Mean retinal and CSI thicknesses correlated negatively with age (p=0.023, r=−0.208 and p<0.0001, r=−0.426, respectively) and axial length (p=0.016, r=−0.220 and p<0.0001, r=−0.504, respectively). To detect a CSI change of at least 112 µm, a sample size of 11 or 36 per group is needed for a single- or double-arm study, respectively (α=0.05, power =0.90, no loss to follow-up, assuming standard deviation in future studies as 100 µm).ConclusionFuture clinical studies using CSI as end point are possible with regard to sample size needed.

Comparison of visual evoked potential monitoring during spine surgeries under total intravenous anesthesia versus balanced general anesthesia

ObjectiveTo determine the comparison of its clinical utility and safety profile for visual evoked potential (VEP) monitoring during prone spine surgeries under total intravenous anesthesia (TIVA) versus balanced general anesthesia using the SightSaver™ visual stimulator. MethodsThe protocol was designed asa pilot, single center, prospective, randomized, and double-arm study. Subjects were randomized to receive either TIVA or balanced general anesthesia. Following induction and intubation, 8 electrodes were placed subcutaneously to collect VEP recordings. The SightSaver™ visual stimulator was placed on the subject’s scalp before prone positioning. VEP waveforms were recorded every 30min and assessed by a neurophysiologist throughout the length of surgery. ResultsA total of 19 subjects were evaluated and VEP waveforms were successfully collected. TIVA group showed higher amplitude and lower latency than balanced anesthesia. ConclusionsOur data suggested that TIVA is associated with higher VEP amplitude and shorter latencies than balanced general anesthesia; therefore, TIVA could be the most efficient anesthesia regimen for VEP monitoring. SignificanceThe findings help to better understand the effect of different anesthesia regimens on intra-operative VEP monitoring.

Usefulness of Structured Video Indirect Ophthalmoscope—Guided Education in Improving Resident Ophthalmologist Confidence and Ability

To evaluate the usefulness of the video indirect ophthalmoscope (VIO) to improve resident ophthalmologist skill with indirect ophthalmoscopy (IO) and scleral depression (SD). Prospective, randomized, double-arm interventional study. Ten ophthalmology residents were enrolled in an educational program using the Heine Video Omega 2C VIO (Heine USA Ltd, Dover, NH) and served as the study group. Ten other experience-matched ophthalmology residents functioned as the control group. At baseline, all study and control residents completed surveys assessing their subjective comfort and skill with IO. Each resident also completed a standardized full IO examination with SD that was recorded using the VIO. Each resident in the study group received 3 monthly 1-hour teaching sessions using the VIO. Surveys and recorded standardized examinations were repeated for all residents after the 3-month period. Both baseline and final examination videos were graded using a standardized grading scale by 3 independent retina faculty members masked to the identities of the residents and timing of the examination. Improved visualization of the peripheral retina (ora serrata) as evaluated by masked graders was the primary outcome measure. Improved examination efficiency grade was the secondary outcome measure. Both the study group and the control group had significant improvement in ability to examine the peripheral retina and ora serrata compared with baseline (P= 0.02 and P= 0.03, respectively). The study group also showed significantly improved examination efficiency compared with baseline, which was not noted in the control group (P= 0.01 and P= 0.53, respectively). The study group self-reported significantly improved confidence in the ability to identify retinal tears, whereas the control group did not (P= 0.003 and P= 0.08, respectively). Study group participants also reported significantly improved ability to recognize retinal holes (P=0.003), subretinal fluid (P= 0.02), and vitreoretinal tufts (P= 0.02), whereas the control group did not. This novel educational study suggests that VIO as part of a structured teaching program may improve resident ophthalmologist confidence and ability with identifying retinal pathologic features using IO with SD.

Intravitreal Injections of Bevacizumab: The Impact of Needle Size in Intraocular Pressure and Pain.

ABSTRACTAim To compare the effect of 30-gauge vs 27-gauge needle size on intraocular pressure (IOP) rise and patients’ pain experience after intravitreal injection (IVI) of bevacizumab.Materials and methods Cross-sectional, randomized, double-armed study. Patients were randomized to IVI with 30-gauge or 27-gauge needle. The IOP was measured pre and post IVI. Patients’ pain was graded using the visual analog scale (VAS).Results A total of 54 eyes were included. The IVI caused a significant IOP rise in both groups (p < 0.001). In the 30-gauge group, the mean pre- and postinjection IOP was 16.3 ± 3.6 mm Hg and 24.1 ± 9.0 mm Hg. The corresponding figures in the 27-gauge group were 18.0 ± 2.54 (p = 0.26) and 23.1 ± 7.5 mm Hg (p = 0.66). In the 30-gauge group, the mean VAS pain score was 3.2 ± 2.6 compared to 3.0 ± 2.5 in the 27-gauge group (p = 0.78).Conclusion The IVI caused a significant rise in IOP after the injection, independently of the needle size used. The 27-gauge needle coursed with lower postinjection IOP without prejudice of the patient comfort.Clinical significance The IVI with 27-gauge may be considered for glaucomatous eyes (higher risk eyes), for which IOP spikes are not recommended.How to cite this article Loureiro M, Matos R, Sepulveda P, Meira D. Intravitreal Injections of Bevacizumab: The Impact of Needle Size in Intraocular Pressure and Pain. J Curr Glaucoma Pract 2017;11(2):38-41.