A randomised clinical trial of the effect of low-level laser therapy for perineal pain and healing after episiotomy: A pilot study

Objective: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy. Design: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment. Setting: the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal, a maternity service located in the city of Sao Paulo, Brazil. Participants: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group. Intervention: in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2 hrs postpartum, between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660 nm (red light), spot size of 0.04 cm(2), energy density of 3.8 J/cm(2), radiant power of 15 mW and 10 s per point, which resulted in an energy of 0.15 J per point and a total energy of 0.45 J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment. Main outcomes: perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women's discharge. Findings: comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy. Conclusions: this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT's effect on perineal pain relief. (C) 2011 Elsevier Ltd. All rights reserved.

Effectiveness of a long-term use of a minimalist footwear versus habitual shoe on pain, function and mechanical loads in knee osteoarthritis: a randomized controlled trial

Background: Recent studies have shown an important reduction of joint overload during locomotion in elderly women with knee osteoarthritis (OA) after short- term use of minimalist shoes. Our aim is to investigate the chronic effect of inexpensive and minimalist footwear on the clinical and functional aspects of OA and gait biomechanics of elderly women with knee OA. Methods/Design: Fifty-six elderly women with knee OA grade 2 or 3 (Kellgren and Lawrence) are randomized into blocks and allocated to either the intervention group, which will use flexible, non-heeled shoes-Moleca (R)-for six months for at least six hours daily, or the control group, which could not use these shoes. Neither group is undergoing physical therapy treatment throughout the intervention period. Moleca (R) is a women's double canvas, flexible, flat walking shoe without heels, with a 5-mm anti-slip rubber sole and a 3-mm internal wedge of ethylene vinyl acetate. Both groups will be followed for six months and will be assessed at baseline condition, after three months, and after six months (end of intervention). All the assessments will be performed by a physiotherapist that is blind to the group allocation. The primary outcome is the pain Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score. The secondary outcomes are global WOMAC score; joint stiffness and disability WOMAC scores; knee pain with a visual analogue scale; walking distance in the six-minute walk test; Lequesne score; amount and frequency (number of days) of paracetamol (500 mg) intake over six months; knee adduction moment during gait; global medical assessment score; and global patient auto-assessment score. At baseline, all patients receive a diary to record the hours of daily use of the footwear intervention; every two weeks, the same physiotherapist makes phone calls to all patients in order to verify adherence to treatment. The statistical analysis will be based on intention to treat analysis, as well as general linear models of analysis of variance for repeated measure to detect treatment-time interactions (alpha = 5%). Discussion: This is the first randomized, clinical trial protocol to assess the chronic effect of minimalist footwear on the clinical and functional aspects and gait biomechanics of elderly women with knee osteoarthritis. We expect that the use of Moleca (R) shoes for six months will provide pain relief, reduction of the knee adduction moment when walking, and improve joint function in elderly women with knee OA, and that the treatment, thus, can be considered another inexpensive and easy-to-use option for conservative OA treatment.

Comparison of application times for ice packs used to relieve perineal pain after normal birth: a randomised clinical trial

Aims and objectives. To compare the effect of an ice pack applied for 10, 15 and 20 minutes to relieve perineal pain after birth. Background. Perineal pain after vaginal birth, with or without vaginal trauma, is one of the most common morbidities reported for postnatal women. Cryotherapy has been used in postpartum period to relieve perineal pain and investigated in several studies. However, cryotherapy treatment protocols in perineal care vary widely regarding temperature, frequency and duration of the application. Design. A controlled trial, randomised for two groups and with a third group as a historical control. Method. The intervention was carried out in a maternity hospital in Sao Paulo, Brazil. The study population consisted of three groups of 38 women who used an ice pack on the perineum, in a single application: group A-10 minutes; group B-15 minutes; group C-20 minutes (historical control from another clinical trial). Participants perineal pain magnitude was evaluated through a numerical scale (010), at four different points: before the cryotherapy; immediately after and at 20 and 40 minutes after cryotherapy. Results. After application of the ice pack, there was no statistical difference when comparing the perineal pain among groups in the second, third and fourth evaluations. Most of the postnatal women reported pain relief, with 72.8% reporting a decrease in pain >50%; 21.9% reported a decrease between 3050%. All postnatal women subjected to cryotherapy were favourable to the procedure. Conclusion. There is no difference in pain scores following ice pack application in three different times (10, 15 and 20 minutes) in women who report moderate or intense perineal pain after normal delivery. Relevance for clinical practice. Ice treatment is safe, and application times of 10 or 15 minutes are as beneficial as an application time of 20 minutes to relieve perineal pain.

High-frequency TENS in post-episiotomy pain relief in primiparous puerpere: A randomized, controlled trial

Aim: We evaluated the effectiveness of high-frequency transcutaneous electrical nerve stimulation (TENS) as a pain relief resource for primiparous puerpere who had experienced natural childbirth with an episiotomy. Methods: A controlled, randomized clinical study was conducted in a Brazilian maternity ward. Forty puerpere were randomly divided into two groups: TENS high frequency and a no treatment control group. Post-episiotomy pain was assessed in the resting and sitting positions and during ambulation. An 11-point numeric rating scale was performed in three separate evaluations (at the beginning of the study, after 60 min and after 120 min). The McGill pain questionnaire was employed at the beginning and 60 min later. TENS with 100 Hz frequency and 75 mu s pulse for 60 min was employed without causing any pain. Four electrodes ware placed in parallel near the episiotomy site, in the area of the pudendal and genitofemoral nerves. Results: An 11-point numeric rating scale and McGill pain questionnaire showed a significant statistical difference in pain reduction in the TENS group, while the control group showed no alteration in the level of discomfort. Hence, high-frequency TENS treatment significantly reduced pain intensity immediately after its use and 60 min later. Conclusion: TENS is a safe and viable non-pharmacological analgesic resource to be employed for pain relief post-episiotomy. The routine use of TENS post-episiotomy is recommended.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number ClinicalTrials.gov: NCT00971165

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Methods We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. Results A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene. Conclusions Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.

Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial

CONTEXT: Compared with bare metal stents, sirolimus-eluting and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study. OBJECTIVE: To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents. DESIGN: Prospective, randomized comparative trial (the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months. SETTING: Ninety hospitals in Europe, Latin America, and Asia. PATIENTS: A total of 1386 patients (mean age, 62.6 years; 73.1% men; 28.0% with diabetes) with angina pectoris and 1 or 2 de novo lesions (2.25-3.00 mm in diameter) in native coronary arteries. INTERVENTION: Patients were randomly assigned in a 1:1 ratio to receive a sirolimus-eluting stent (n = 701) or a paclitaxel-eluting stent (n = 685). MAIN OUTCOME MEASURES: The primary end point was in-lesion binary restenosis (presence of a more than 50% luminal-diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non-Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization. RESULTS: In-lesion binary restenosis at 8 months occurred in 86 patients (9.6%) with a sirolimus-eluting stent vs 95 (11.1%) with a paclitaxel-eluting stent (relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P = .31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean (SD) in-stent late loss was 0.09 (0.43) mm vs 0.31 (0.44) mm (difference, -0.22 mm; 95% CI, -0.26 to -0.18 mm; P<.001), mean (SD) in-stent diameter stenosis was 23.1% (16.6%) vs 26.7% (15.8%) (difference, -3.60%; 95% CI, -5.12% to -2.08%; P<.001), and the number of major adverse cardiac events at 1 year was 73 (10.7%) vs 76 (11.4%) (RR, 0.94; 95% CI, 0.69-1.27; P = .73). CONCLUSION: In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00235092.

Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: a randomized controlled trial

OBJECTIVE: To compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee. METHODS: This was a multicenter, patient-blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross-linked hylan, a non-cross-linked medium molecular weight HA of avian origin, or a non-cross-linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7-12, patients were offered a second cycle of viscosupplementation. RESULTS: Pain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] -0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI -2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]). CONCLUSION: We found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.

Pain relief in ventilated preterms during endotracheal suctioning: a randomized controlled trial

BACKGROUND: In Switzerland approximately 8% of infants are born prematurely. Some of them undergo mechanical ventilation including endotracheal suctioning (ETS). ETS is one of the most frequently performed interventions and is linked to stress and pain, but its treatment is controversial. In Switzerland there is a lack of standardisation in pain relief for ETS. AIMS: To test the hypothesis that an intermittent dose of morphine reduces pain during ETS and that subsequent multisensorial stimulation (MSS), as a non pharmacological comforting intervention, helps infants to recover from experienced pain. METHOD: A randomized placebo controlled trial in two tertiary neonatal intensive care units (NICU) with a sample of 30 mechanically ventilated preterm infants was conducted. Pain was measured by three pain assessment tools (Bernese Pain Scale for Neonates, Premature Infant Pain Profile and Visual Analogue Scale) RESULTS: Morphine did not lead to any pain relief from ETS as measured by three pain scales. Nor did the comforting intervention of MSS show any effect. Repeated-measure analysis of variance for the within and between groups comparison showed no statistical significance. CONCLUSIONS: The administration of morphine for pain relief in ventilated preterm neonates during ETS remains questionable and the use of MSS as a comforting intervention after painful stimulus cannot be recommended. The validity testing of the instruments for this patient population should undergo a systematic validation trajectory. Future research should focus on options among non pharmacological interventions for relieving pain during ETS.

Effectiveness of a calcium sodium phosphosilicate-containing prophylaxis paste in reducing dentine hypersensitivity immediately and 4 weeks after a single application: a double-blind randomized controlled trial

AIMS The aim of this single-site, randomized, controlled, double-blind, 3-arm parallel study was to determine the effectiveness of a prophylaxis paste containing 15% calcium sodium phosphosilicate (CSPS; NovaMin(®) ) with and without fluoride in reducing dentine hypersensitivity immediately after a single application and 28 days following dental scaling and root planing. MATERIALS & METHODS Overall, 151 subjects were enrolled in this study. All subjects received a scaling and root planing procedure followed by a final prophylaxis step using one of three different prophylaxis pastes: Test-A (15% NovaMin(®) and NaF), Test-B (15% NovaMin(®) ) and a control. Dentine hypersensitivity was assessed by tactile stimulus (Yeaple Probe(®) ) and by air blast (Schiff scale) at baseline, immediately after and 28 days after a prophylaxis procedure. One hundred and forty-nine subjects completed the study. RESULTS Subjects having received the test prophylaxis pastes showed statistically lower (anova, p < 0.05) dentine hypersensitivity compared with the control group immediately after the prophylaxis procedure (Yeaple Probe(®) : Test-A = 20.9 ± 12.6, Test-B = 22.7 ± 12.9, Control=11.2 ± 3.1; Schiff score: Test-A = 1.1 ± 0.6, Test-B = 1.1 ± 0.6, Control = 2.0 ± 0.7) and after 28 days (Yeaple probe: Test-A = 21.5 ± 11.9, Test-B = 20.6 ± 11.3, Control = 11.8 ± 6.0; Schiff score: Test-A = 1.0 ± 0.6, Test-B = 1.0 ± 0.6, Control = 2.0 ± 0.7). CONCLUSIONS In conclusion, the single application of both fluoridated and non-fluoridated prophylaxis pastes containing 15% CSPS (NovaMin(®) ) provided a significant reduction of dentine hypersensitivity up to at least 28 days.

Does a Pre-Treatment Diagnostic Interview Affect the Outcome of Internet-Based Self-Help for Social Anxiety Disorder? A Randomized Controlled Trial

BACKGROUND: Numerous studies suggest that Internet-based self-help treatments are effective in treating anxiety disorders. Trials evaluating such interventions differ in their screening procedures and in the amount of clinician contact in the diagnostic assessment phase. The present study evaluates the impact of a pre-treatment diagnostic interview on the outcome of an Internet-based treatment for Social Anxiety Disorder (SAD). METHOD: One hundred and nine participants seeking treatment for SAD were randomized to either an interview-group (IG, N = 53) or to a non-interview group (NIG, N = 56). All participants took part in the same 10-week cognitive-behavioural unguided self-help programme. Before receiving access to the programme, participants of the IG underwent a structured diagnostic interview. Participants of the NIG started directly with the programme. RESULTS: Participants in both groups showed significant and substantial improvement on social anxiety measures from pre- to post-assessment (d IG = 1.30-1.63; d NIG = 1.00-1.28) and from pre- to 4-month follow-up assessment (d IG = 1.38-1.87; d NIG = 1.10-1.21). Significant between-groups effects in favour of the IG were found on secondary outcome measures of depression and general distress (d = 0.18-0.42). CONCLUSIONS: These findings suggest that Internet-based self-help is effective in treating SAD, whether or not a diagnostic interview is involved. However, the pre-treatment interview seems to facilitate change on secondary outcomes such as depression and general distress.

Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the incidence of posttraumatic stress after acute myocardial infarction through trauma-focused psychological counseling: study protocol for a randomized controlled trial

BACKGROUND Posttraumatic Stress Disorder (PTSD) may occur in patients after exposure to a life-threatening illness. About one out of six patients develop clinically relevant levels of PTSD symptoms after acute myocardial infarction (MI). Symptoms of PTSD are associated with impaired quality of life and increase the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT study is that trauma-focused psychological counseling is more effective than non-trauma focused counseling in preventing posttraumatic stress after acute MI. METHODS/DESIGN The study is a single-center, randomized controlled psychological trial with two active intervention arms. The sample consists of 426 patients aged 18 years or older who are at 'high risk' to develop clinically relevant posttraumatic stress symptoms. 'High risk' patients are identified with three single-item questions with a numeric rating scale (0 to 10) asking about 'pain during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless when being told about having MI'. Exclusion criteria are emergency heart surgery, severe comorbidities, current severe depression, disorientation, cognitive impairment and suicidal ideation. Patients will be randomly allocated to a single 45-minute counseling session targeting either specific MI-triggered traumatic reactions (that is, the verum intervention) or the general role of psychosocial stress in coronary heart disease (that is, the control intervention). The session will take place in the coronary care unit within 48 hours, by the bedside, after patients have reached stable circulatory conditions. Each patient will additionally receive an illustrated information booklet as study material. Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk factors will be assessed during hospitalization. The primary outcome is the interviewer-rated posttraumatic stress level at three-month follow-up, which is hypothesized to be at least 20% lower in the verum group than in the control group using the t-test. Secondary outcomes are posttraumatic stress levels at 12-month follow-up, and psychosocial functioning and cardiometabolic risk factors at both follow-up assessments. DISCUSSION If the verum intervention proves to be effective, the study will be the first to show that a brief trauma-focused psychological intervention delivered within a somatic health care setting can reduce the incidence of posttraumatic stress in acute MI patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01781247.

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm(®) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622).

BACKGROUND Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria. OBJECTIVE We conducted the first clinical trial with the novel PlasmaDerm(®) VU-2010 device to assess safety and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers. METHODS From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak(®) , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires). RESULTS The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm(®) VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial

BACKGROUND Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION 7 September 2009 on ClinicalTrials.gov: NCT00973154.