Lack Of Adverse Events Research Articles

Efficacy of cola ingestion for oesophageal food bolus impaction: open label, multicentre, randomised controlled trial

ObjectiveTo determine the efficacy and safety of cola in resolving complete oesophageal food bolus impaction.DesignOpen label, multicentre, randomised controlled trial.SettingEmergency departments of five Dutch hospitals at the secondary and tertiary...

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study

PurposeMeniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. Materials and methodsThis study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A–F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. ResultsBefore treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. ConclusionsLow-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

Implementation of a nurse-led multidisciplinary huddle meeting for improvement of early rehabilitation in ICU: a healthcare quality improvement project

The physical decline of critically ill patients affects their discharge from the intensive care unit (ICU) and their subsequent lives. Therefore, it is essential to actively provide rehabilitation at an...

RAAV-PHP.B escapes the mouse eye and causes lethality whereas rAAV9 can transduce aniridic corneal limbal stem cells without lethality.

Recently safety concerns have been raised in connection with high doses of recombinant adeno-associated viruses (rAAV). Therefore, we undertook a series of experiments to test viral capsid (rAAV9 and rAAV-PHP.B), dose, and route of administration (intrastromal, intravitreal, and intravenous) focused on aniridia, a congenital blindness that currently has no cure. The success of gene therapy for aniridia may depend on the presence of functional limbal stem cells (LSCs) in the damaged aniridic corneas and whether rAAV can transduce them. Both these concerns were unknown, and thus were also addressed by our studies. For the first time, we report ataxia and lethality after intravitreal or intrastromal rAAV-PHP.B virus injections. We demonstrated virus escape from the eye and transduction of non-ocular tissues by rAAV9 and rAAV-PHP.B capsids. We have also shown that intrastromal and intravitreal delivery of rAAV9 can transduce functional LSCs, as well as all four PAX6-expressing retinal cell types in aniridic eye, respectively. Overall, lack of adverse events and successful transduction of LSCs and retinal cells makes it clear that rAAV9 is the capsid of choice for future aniridia gene therapy. Our finding of rAAV lethality after intraocular injections will be impactful for other researchers developing rAAV-based gene therapies.

Cognitive Training to Enhance Aphasia Therapy (Co-TrEAT): A Feasibility Study.

Persons with aphasia (PWA) often have deficits in cognitive domains such as working memory (WM), which are negatively correlated with recovery, and studies have targeted WM deficits in aphasia therapy. To our knowledge, however, no study has examined the efficacy of multi-modal training which includes both WM training and targeted language therapy. This pilot project examined the feasibility and preliminary efficacy of combining WM training and naming therapy to treat post-stroke PWA. Chronic PWA were randomly assigned to either the a) Phonological Components Analysis (PCA) and WM intervention (WMI) condition (i.e., a computerized adaptive dual n-back task), or b) PCA and active control condition (WMC). Participants received face-to-face PCA therapy 3 times/week for 5 weeks, and simultaneously engaged in WM training or the active control condition five times/week, independently at home. Six PWA were enrolled, 3 in each condition. Feasibility metrics were excellent for protocol compliance, retention rate and lack of adverse events. Recruitment was less successful, with insufficient participants for group analyses. Participants in the WMI (but not the WMC) condition demonstrated a clinically significant (i.e., > 5 points) improvement on the Western Aphasia Battery- Aphasia Quotient (WAB-R AQ) and Boston Naming Test after therapy. Given the small sample size, the performance of two individuals, matched on age, education, naming accuracy pre-treatment, WAB-R AQ and WM abilities was compared. Participant WMI-3 demonstrated a notable increase in WM training performance over the course of therapy; WMC-2 was the matched control. After therapy, WMI-3's naming accuracy for the treated words improved from 30 to 90% (compared to 30–50% for WMC-2) with a 7-point WAB-R AQ increase (compared to 3 for WMC-2). Improvements were also found for WMI-3 but not for WMC-2 on ratings of communicative effectiveness, confidence and some conversation parameters in discourse. This feasibility study demonstrated excellent results for most aspects of Co-TrEAT. Recruitment rate, hampered by limited resources, must be addressed in future trials; remotely delivered aphasia therapy may be a possible solution. Although no firm conclusions can be drawn, the case studies suggest that WM training has the potential to improve language and communication outcomes when combined with aphasia therapy.

Assessment of Beta-2 Microglobulin Gene Edited Airway Epithelial Stem Cells as a treatment for Sulfur Mustard Inhalation.

Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there are no fielded therapeutics that are specific for such injuries. Previous studies reported that SM inhalation depleted the tracheobronchial airway epithelial stem cell (TSC) pool and supported the hypothesis, TSC replacement will restore airway epithelial integrity and improve health outcomes for SM-exposed individuals. TSC express Major Histocompatibility Complex (MHC-I) transplantation antigens which increases the chance that allogeneic TSC will be rejected by the patient’s immune system. However, previous studies reported that Beta-2 microglobulin (B2M) knockout cells lacked cell surface MHC-I and suggested that B2M knockout TSC would be tolerated as an allogeneic graft. This study used a Cas9 ribonucleoprotein (RNP) to generate B2M-knockout TSC, which are termed Universal Donor Stem Cells (UDSC). Whole genome sequencing identified few off-target modifications and demonstrated the specificity of the RNP approach. Functional assays demonstrated that UDSC retained their ability to self-renew and undergo multilineage differentiation. A preclinical model of SM inhalation was used to test UDSC efficacy and identify any treatment-associated adverse events. Adult male Sprague-Dawley rats were administered an inhaled dose of 0.8 mg/kg SM vapor which is the inhaled LD50 on day 28 post-challenge. On recovery day 2, vehicle or allogeneic Fisher rat UDSC were delivered intravenously (n = 30/group). Clinical parameters were recorded daily, and planned euthanasia occurred on post-challenge days 7, 14, and 28. The vehicle and UDSC treatment groups exhibited similar outcomes including survival and a lack of adverse events. These studies establish a baseline which can be used to further develop UDSC as a treatment for SM-induced airway disease.

Abstract WP141: Effect Of Non-invasive Vagus Nerve Stimulation In Hemorrhagic Brain Injury And Permanent Ischemic Stroke In Rats

Introduction: Non-invasive vagus nerve stimulation (nVNS) reduces infarct volume after transient ischemia in rats. Here, we tested the effect of nVNS in intracerebral hemorrhage (ICH) and permanent ischemic brain injury models. Methods: ICH was induced by whole blood (n=24) or collagenase (n=24) injection into the striatum of adult male and female Wistar rats. 1-hour sham stimulation (n=16) or nVNS (n=32) was initiated 30 minutes after injection. Spontaneous circling, hindlimb retraction, and grasp ability were tested at 24 hours to measure functional deficit. Rats were euthanized 24 hours or one week after injury, and brain tissue was processed for water content analysis (n=24) and histology (n=24), respectively. Permanent ischemia was induced by filament occlusion of the right middle cerebral artery in adult male Wistar rats (n=18). Sham stimulation and nVNS initiated 30 minutes after the induction of ischemia were applied for 1 hour and 3 hours (n=6 per group). Rats were euthanized 24 hours later to measure infarct volume. Results: 1-hour nVNS was associated with a non-significant reduction in hematoma volume in both models of ICH (Fig). Animals treated with nVNS demonstrated better functional outcome at 24 hours after ICH ( p =0.042). There was no difference in brain edema between control and active treatment arms in both models of ICH. 3-hour nVNS reduced infarct volume by 21% in permanent ischemia ( p =0.047, Fig). Conclusion: The results of this study support prior evidence that nVNS may have a therapeutic potential in ischemic stroke. nVNS is currently being evaluated in two clinical studies (NCT03733431 and NCT04050501) for the treatment of acute ischemic stroke. The lack of adverse events in two different models of ICH in this study suggests that nVNS could be safely administered as early as an ambulatory setting before the stroke etiology (ischemic vs. hemorrhagic) has been determined.

Initial Experience with a Bioresorbable Polymer Anchor

Category:Ankle; Ankle ArthritisIntroduction/Purpose:Anchors are frequently used in reconstructive orthopedic surgery to achieve fixation of soft tissue to bone. Anchors vary with respect to material composition, configuration, and methods of fixation at the site of attachment. The fixation component of anchoring devices has generally evolved from metal-fabricated implants to various types of bioresorbable anchors. The SonicAnchorTM (Stryker, Kalamazoo, MI USA) polymer implant provides a unique form of anchor fixation using SonicFusionTM technology to achieve interdigitation within cancellous bone while being radiolucent and providing a small footprint.Methods:During a four-year period, 116 patients underwent a reconstructive orthopedic foot and ankle surgical procedure with the use of at least one bioresorbable polymer anchor (SonicAnchor implant). There were 59 males and 57 females, with an average age of 42 years (range: 12-83 years).Results:A total of 233 bioresorbable anchor (SonicAnchor) implants were used in 116 patients. Of the 116 patients, 108 (93.1%) achieved successful clinical healing of their surgery at their most recent follow-up. The average follow-up duration was 309 days (range: 14-1,429 days). Eight (6.9%) patients were lost to follow-up prior to clinical healing. Two (1.7%) patients underwent reoperation. Also, 65 (56%) patients had at least six months of follow-up and 36 (31%) had at least one year of follow-up.Conclusion:This preliminary clinical trial of patients undergoing soft tissue repair or reconstruction with a bioresorbable polymer appears to perform comparably to other commercially available devices. The lack of adverse events, mechanical failures, or infections further supports the safety of this device.

Evaluation of solvent/detergent-treated plasma safety and efficacy in orthotopic liver transplant and thrombotic thrombocytopenic purpura patients: A single center experience.

Solvent/detergent-treated, pooled plasma (SDP) is approved for use in orthotopic liver transplantation (OLT) and thrombotic thrombocytopenic purpura (TTP) patients; however, studies evaluating safety and effectiveness of SDP in these populations are limited. This prospective study included two cohorts: OLT patients (n=40) who received either SDP (n=20) or FFP (control group) (n=20), and TTP patients (n=20) who received either SDP (n=10) or FFP (control group) (n=10) throughout hospitalization. Medical, laboratory, and blood bank records were retroactively assessed for both cohorts for differences in clinical outcomes, laboratory values, and transfusion data from admission to discharge. In the OLT cohort, significant changes in AST and ALP were observed in the control group as compared to SDP (p< .05 each), and creatinine levels improved significantly in the SDP group as compared to the control group (p< .05) from admission to discharge. In the TTP cohort, platelet counts were significantly improved within the control and SDP groups from admission to discharge, but there were no significant differences between groups (p=.31). LDH levels improved between admission and discharge for both groups (70% decrease in the control group, p < .001, and 80% decrease in the SDP group, p=.001). There were no significant differences detected in clinical outcomes in either cohort. As evidenced by the lack of adverse events in either cohort and similar clinical outcomes, we conclude that SDP is comparable in safety and effectiveness to FFP in OLT and TTP patients. Further studies are needed to evaluate the potential for improved safety with SDP.

Action Observation Therapy for Upper Limb Recovery in Patients with Stroke: A Randomized Controlled Pilot Study.

Due to the complexity of the interventions for upper limb recovery, at the moment there is a lack of evidence regarding innovative and effective rehabilitative interventions. Action Observation Training (AOT) constitutes a promising rehabilitative method to improve upper limb motor recovery in stroke patients. The aim of the present study was to evaluate the potential efficacy of AOT, both in upper limb recovery and in functional outcomes when compared to patients treated with task oriented training (TOT). Both treatments were added to traditional rehabilitative treatment. Thirty-two acute stroke patients at 15.6 days (±8.3) from onset, with moderate to severe upper limb impairment at baseline following their first-ever stroke, were enrolled and randomized into two groups: 16 in the experimental group (EG) and 16 in the control group (CG). The EG underwent 30 min sessions of AOT, and the CG underwent 30 min sessions of TOT. All participants received 20 sessions of treatment for four consecutive weeks (five days/week). The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Box and Block Test (BBT), Functional Independence Measure (FIM) and Modified Ashworth Scale (MAS) were administered at baseline (T0) and at the end of treatment (T1). No statistical differences were found at T0 for inclusion criteria between the CG and EG, whereas both groups improved significantly at T1. After the treatment period, the rehabilitative gain was greater in the EG compared to the CG for FMA-UE and FIM (all p < 0.05). Our results suggest that AOT can contribute to increased motor recovery in subacute stroke patients with moderate to severe upper limb impairment in the early phase after stroke. The improvements presented in this article, together with the lack of adverse events, confirm that the use of AOT should be broadened out to larger pools of subacute stroke patients.

Delayed-Release Phosphatidylcholine Is Effective for Treatment of Ulcerative Colitis: A Meta-Analysis

Background: Phosphatidylcholine (PC) is intrinsically missing in intestinal mucus of patients with ulcerative colitis. Topical supplementation with delayed intestinal release PC formulations is assumed to compensate this lack. Three monocenter randomized controlled trials (RCTs) with a 30% PC-containing lecithin were successful, whereas 1 trial with >94% PC-containing lecithin failed. Objectives: Evaluation of 30% PC-containing lecithin provided in a delayed intestinal release formulation for treatment efficacy of ulcerative colitis was evaluated by meta-analysis of 3 RCTs. Methods: Meta-analysis of 3 studies was performed using RevMan 5.3 software. Odds ratio (OR) and 95% Cl were calculated for remission, clinical and endoscopic improvement, histology, and life quality. p values <0.05 were accepted as significant. Results: The meta-analysis of 3 RTCs with 160 included patients with ulcerative colitis verified that PC improved the rate of remission (OR = 9.68), as well as clinical (OR = 30.58) and endoscopic outcomes (OR = 36.73). Within the available patient population, also histology and quality of life became better. All effects were significant over placebo. Achieved remission was maintained in a higher percentage of patients under intestinal-release PC formulation than placebo. The profile of adverse events was identical to the placebo population. Conclusions: A 30% PC-containing lecithin in delayed intestinal release formulation improves clinical and endoscopic outcomes, histologic activity, and quality of life in patients with ulcerative colitis. For the patients, lack of adverse events is an important consideration.

Initial Experience With a Bioresorbable Polymer Anchor.

BackgroundAnchors are frequently used in reconstructive orthopedic surgery to achieve fixation of soft tissue to bone. Anchors vary with respect to material composition, configuration, and methods of fixation at the site of attachment. The fixation component of anchoring devices has generally evolved from metal-fabricated implants to various types of bioresorbable anchors. The SonicAnchorTM (Stryker, Kalamazoo, MI USA) polymer implant provides a unique form of anchor fixation using SonicFusionTM technology to achieve interdigitation within cancellous bone while being radiolucent and providing a small footprint.MethodsDuring a four-year period, 116 patients underwent a reconstructive orthopedic foot and ankle surgical procedure with the use of at least one bioresorbable polymer anchor (SonicAnchor implant). There were 59 males and 57 females, with an average age of 42 years (range: 12-83 years).ResultsA total of 233 bioresorbable anchor (SonicAnchor) implants were used in 116 patients. Of the 116 patients, 108 (93.1%) achieved successful clinical healing of their surgery at their most recent follow-up. The average follow-up duration was 309 days (range: 14-1,429 days). Eight (6.9%) patients were lost to follow-up prior to clinical healing. Two (1.7%) patients underwent reoperation. Also, 65 (56%) patients had at least six months of follow-up and 36 (31%) had at least one year of follow-up.ConclusionsThis preliminary clinical trial of patients undergoing soft tissue repair or reconstruction with a bioresorbable polymer appears to perform comparably to other commercially available devices. The lack of adverse events, mechanical failures, or infections further supports the safety of this device.

Administration of intravenous iron and tranexamic acid in the management of postoperative iron deficiency anaemia following free flap reconstruction: re-audit

Following free tissue transfer, intravenous iron (IVI) has a role in reducing the rates of blood transfusion and more rapidly restoring haemoglobin (Hb) levels. Anaemia has a detrimental effect on survival, postoperative complications, fatigue, and health-related quality of life, therefore early correction is recommended. The aim of this re-audit is to assess the use of IVI, of tranexamic acid intraoperatively, and of perioperative blood transfusions. A total of 148 consecutive patients who underwent ablative surgery and free flap reconstruction between May 2018 and September 2019 were audited. The median (IQR) age was 66 (59,72) years and 36% were female. For two-thirds, surgery was for cancer located in the oral cavity and two-thirds of the free flaps were soft tissue. Tranexamic acid (TXA) was used intraoperatively for 30%, red blood cells (RBC) were transfused for 20% and 55 patients (37%) received IV iron. This compares with 4%, 26%, and 0, respectively, in the initial audit. Those having IVI were more likely (56%) to have had a composite flap, a lower postoperative haemoglobin and lower discharge Hb. The Hb between four and twelve weeks’ follow up, known for 40, was a median (IQR) of 122 (104,138). There were no adverse reactions to IV iron. Although it is straightforward to administer IVI postoperatively, this re-audit demonstrates that it can be a challenge to embed change in protocols. Through raised awareness of the benefits of IVI, lack of adverse events and clarification of selection criteria, it is hoped that rates of IVI use will increase.

Yoghurt-induced Lactobacillus bacteremia in a patient with Crohn's disease on therapy with ustekinumab and concomitant HIV-Infection

Probiotics are live microorganisms that are often used as adjunctive therapy in patients with inflammatory bowel disease. Although there is a lack of evidence for their benefit, the use of probiotics is encouraged by the perceived lack of adverse events. However, in rare instances, probiotics can cause systemic infections through bacteremia. We report about a patient with Crohn's disease and HIV-infection, who developed a septicemia. A Lactobacillus-bacteremia was diagnosed, the causative agents could be traced back to the consumption of self-made yoghurt. The utility of probiotics in IBDpatients with underlying immune-compromising diseases is a risk which is difficult to predict, therefore their use in these patients should be discouraged.

P258 Real-world secukinumab retention, response rates and adverse events in the treatment of PsA and axSpA

Abstract Background Secukinumab, an IL-17A inhibitor, has been licensed for use in the United Kingdom for both axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) for several years. Despite this there is minimal published data on its use out with randomised controlled trials. We present here the collated real-world rheumatology experience of secukinumab use in Glasgow. Methods Patients who have ever received secukinumab for any rheumatology indication were identified using available medical records (from 14/05/2012 to 18/09/2019). Diagnosis, baseline demographics, disease activity at baseline and at 6 months, and whether patients are still currently on secukinumab was recorded. Primary inefficacy was defined as stopping treatment due to inefficacy ≤6 months. Reasons for discontinuation were also recorded. As disease activity scores were variably recorded, the primary outcome was retention rate as a surrogate for efficacy and lack of adverse event. Patients only included in disease scores if scores available both at baseline and 6 months. Results 352 patients (with 530 patient-years of exposure) identified. 251 (71.3%) patients currently remain on secukinumab. 301 of 336 (89.6%) patients remained on drug at six-month review (16 await review). Characteristics and response of two main diagnostic groups listed in Table 1 (Note: 3 patients had SAPHO, 5 had Juvenile Idiopathic Arthritis, 1 had reactive arthritis). Common adverse events were infections (11 patients), rash and/or pruritis (6 patients), mood change and/or fatigue (4 patients). Three patients developed inflammatory bowel disease (IBD) subsequent to starting secukinumab. Five patients had pre-existing IBD, none of which flared on secukinumab. Two patients required hospitalisation for abscesses whilst on secukinumab. One patient had a stroke and one patient had a myocardial infarction whilst on secukinumab - both patients had multiple risk factors for cardiovascular disease. No malignancies identified. Three patients died, with none felt related to secukinumab (cerebellar haemorrhage in warfarinised patient with high INR; pneumonia six months after switching from secukinumab to tocilizumab; one out of hospital death over one year after stopping secukinumab). Conclusion In this real world cohort of patients with axSpA and PsA, secukinumab retention rates at 6 months are high with no new safety signals identified. Disclosures A. Tindell None. S. Batool None. A. McGucken None. S. Siebert Consultancies; S.S. has received speaker or consultation fees or honoraria from AbbVie, UCB, Janssen, Boehringer Ingelheim, Novartis, Celgene. Honoraria: S.S. has received speaker or consultation fees or honoraria from AbbVie, UCB, Janssen, Boehringer Ingelheim, Novartis, Celgene. Grants/research support; S.S has received funding for research/ grants from Pfizer, Janssen, BMS, Celgene, UCB, Boehringer Ingelheim, Novartis, GSK.

Medical Gas Plasma Treatment in Head and Neck Cancer—Challenges and Opportunities

Despite progress in oncotherapy, cancer is still among the deadliest diseases in the Western world, emphasizing the demand for novel treatment avenues. Cold physical plasma has shown antitumor activity in experimental models of, e.g., glioblastoma, colorectal cancer, breast carcinoma, osteosarcoma, bladder cancer, and melanoma in vitro and in vivo. In addition, clinical case reports have demonstrated that physical plasma reduces the microbial contamination of severely infected tumor wounds and ulcerations, as is often seen with head and neck cancer patients. These antimicrobial and antitumor killing properties make physical plasma a promising tool for the treatment of head and neck cancer. Moreover, this type of cancer is easily accessible from the outside, facilitating the possibility of several rounds of topical gas plasma treatment of the same patient. Gas plasma treatment of head and neck cancer induces diverse effects via the deposition of a plethora of reactive oxygen and nitrogen species that mediate redox-biochemical processes, and ultimately, selective cancer cell death. The main advantage of medical gas plasma treatment in oncology is the lack of adverse events and significant side effects compared to other treatment modalities, such as surgical approaches, chemotherapeutics, and radiotherapy, making plasma treatment an attractive strategy for the adjuvant and palliative treatment of head and neck cancer. This review outlines the state of the art and progress in investigating physical plasma as a novel treatment modality in the therapy of head and neck squamous cell carcinoma.

Framework for development of urgent care services towards strengthening primary healthcare in India - Joint position paper by the Academy of Family Physician of India and the Academic College of Emergency Experts.

Urgent care practice (UCP) is a novel concept for India. Urgent care primarily deals with injuries or illnesses requiring immediate care. Medical emergency and urgency can happen anywhere unannounced. Research has shown that 90% of the morbidities can be resolved within the community by primary care physicians lead teams. Given the changing professional demands, non-specialists tend to refer away far too many cases to specialists, undermining generalist medical care, particularly in Indian settings. The spillover of the patient load from the primary care setting to the tertiary care centers is enormous leading to resource mismatch. Family physicians and other primary care providers are best positioned to develop practices and provide good quality urgent care to society. Family physicians, general practitioners, and medical officers are already functioning as the frontline care providers for any emergency or medical urgency arising within communities. Urgent care is essentially ambulatory care or outpatient care outside of a traditional hospital emergency room. “UCP aims to provide timely support, which is easily accessible with a focus on good clinical outcomes, e.g. survival, recovery, lack of adverse events, and complications. Core interventions of urgent care are centered on the 4Rs - Rescue, Resuscitate, Relate, and Refer. At present, there are no available, established training model for future faculty, residents, and medical students on “UCP“ in India.

An exploratory parallel-group randomised controlled trial of antenatal Guided Self-Help (plus usual care) versus usual care alone for pregnant women with depression: DAWN trial

BackgroundDepression is a common antenatal mental disorder associated with significant maternal morbidity and adverse fetal outcomes. However, there is a lack of research on the effectiveness or cost-effectiveness of psychological interventions for antenatal depression. MethodsA parallel-group, exploratory randomised controlled trial across five hospitals. The trial compared Guided Self-Help, modified for pregnancy, plus usual care with usual care alone for pregnant women meeting DSM-IV criteria for mild-moderate depression. The trial objectives were to establish recruitment/follow-up rates, compliance and acceptability, and to provide preliminary evidence of intervention efficacy and cost-effectiveness. The primary outcome of depressive symptoms was assessed by blinded researchers using the Edinburgh Postnatal Depression Scale at 14-weeks post-randomisation. Results620 women were screened, 114 women were eligible and 53 (46.5%) were randomised. 26 women received Guided Self-Help – 18 (69%) attending ≥4 sessions - and 27 usual care; n = 3 women were lost to follow-up (follow-up rate for primary outcome 92%). Women receiving Guided Self-Help reported fewer depressive symptoms at follow-up than women receiving usual care (adjusted effect size −0.64 (95%CI: −1.30, 0.06) p = 0.07). There were no trial-related adverse events. The cost-effectiveness acceptability curve showed the probability of Guided Self-Help being cost-effective compared with usual care ranged from 10 to 50% with a willingness-to-pay range from £0 to £50,000. Conclusions and LimitationsDespite intense efforts we did not meet our anticipated recruitment target. However, high levels of acceptability, a lack of adverse events and a trend towards improvements in symptoms of depression post-treatment indicates this intervention is suitable for talking therapy services.

Disposable Patterned Electroceutical Dressing (PED-10) Is Safe for Treatment of Open Clinical Chronic Wounds.

Objective: To evaluate if patterned electroceutical dressing (PED) is safe for human chronic wounds treatment as reported by wound care providers. Approach: This work reports a pilot feasibility study with the primary objective to determine physically observable effects of PED application on host tissue response from a safety evaluation point of view. For this pilot study, patients receiving a lower extremity amputation with at least one open wound on the part to be amputated were enrolled. Patients were identified through the Ohio State University Wexner Medical Center (OSUWMC) based on inclusion and exclusion criteria through prescreening through the Comprehensive Wound Center's (CWC) Limb Preservation Program and wound physicians and/or providers at OSUWMC. Wounds were treated with the PED before amputation surgery. Results: The intent of the study was to identify if PED was safe for clinical application based on visual observations of adverse or lack of adverse events on skin and wound tissue. The pilot testing performed on a small cohort (N = 8) of patients showed that with engineered voltage regulation of current flow to the open wound, the PED can be used with little to no visually observable adverse effects on chronic human skin wounds. Innovation: The PED was developed as a second-generation tunable electroceutical wound care dressing, which could potentially be used to treat wounds with deeper infections compared with current state of the art that treats wounds with treatment zone limited to the surface near topical application. Conclusion: Technology advances in design and fabrication of electroceutical dressings were leveraged to develop a tunable laboratory prototype that could be used as a disposable low-cost electroceutical wound care dressing on chronic wounds. Design revisions of PED-1 (1 kΩ ballast resistor) circumvented previously observed adverse effects on the skin in the vicinity of an open wound. PED-10 (including a 10 kΩ ballast resistor) was well tolerated in the small cohort of patients (N = 8) on whom it was tested, and the observations reported here warrant a larger study to determine the clinical impact on human wound healing and infection control.

Abstract: The Impact of N-Acetylcysteine on Autologous Fat Graft - First-in-Human Pilot Study

The aim of this pilot study was to determine whether N-acetylcysteine (NAC) administered at the fat graft donor site during the harvest procedure reduces oxidative stress and thus, improves graft survivability. The study included 15 women with mean age of 31.8 years (range, 23–39 years). A 200-ml adipose tissue graft was harvested from each thigh in each study subject. The procedure of graft harvesting from one thigh, considered as the control (n=15), included infiltration with a standard tumescent fluid. During harvesting the graft from the other thigh, a tumescent fluid containing NAC (Sandoz, Holzkirchen, Germany) was used (NAC group, n=15). Plastic surgeon who conducted the procedure was blinded to the type of administered fluid. All patients were followed-up for 6-months for potential adverse events associated with administration of the modified tumescent fluid. A 65-ml adipose tissue sample from each graft was subjected to immediate and postponed biochemical analysis, flow cytometric assay and Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). The rest of the graft was used for correction of breast asymmetry, to determine the degree of fat resorption based on the comparison of pre- and postoperative MRI findings (separate study). During biochemical tests, the severity of oxidative stress was determined based on the levels of reactive oxygen species (ROS) and nitric oxide (NO), along with the concentration and activity of superoxide dismutase (SOD). qRT-PCR analysis included targets linked with oxidative stress (GPX-3, hsCAT, hsSOD, iNOS, HO-1), angiogenesis (VEGF, ANG-2) and adipogenesis (PPAR-γ, C/EBP β). Normal distribution of the study variables was verified with Kolmogorov-Smirnov test. Intragroup comparisons were carried out with Wilcoxon signed-rank test. All calculations were conducted with Statistica 10 (StatSoft, Tulsa, OK, USA), with the threshold of statistical significance set at p<0.05. Neither local nor systemic postoperative complications were observed in the study subjects during a 6-month follow-up. Concentration of SOD in the NAC group turned out to be significantly higher than in the controls, in both fresh (p=0.041) and frozen samples (p=0.004). Also SOD activity in NAC group was significantly higher, both in fresh and frozen samples (p=0.023 and p=0.003, respectively). Interestingly, no statistically significant intergroup differences were observed in terms of ROS levels. The level of NO in frozen samples from the controls was significantly higher than in NAC group (p=0.009). The only qRT-PCR target showing significant intergroup differences was iNOS (encoding inducible NO synthase), with higher transcription levels observed in the controls (p=0.027). The results of this study imply that addition of NAC to tumescent solution may counteract oxidative stress the cells of autologous fat graft are exposed to during the harvesting procedure. This may contribute to lesser volume of the graft that undergoes resorption over time (the study is still ongoing). The lack of adverse events after the infiltration of the fat graft donor site with NAC-enriched solution suggests that this technique is safe. If addition of NAC was shown to improve the retention of the graft, this technique might become a routine adjunct method used during this type of procedures.