Nebulized Heparin in Burn Patients with Inhalation Trauma—Safety and Feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients.

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Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽

10.1136/bmjopen-2020-047993 ◽

2021 ◽

Vol 11 (5) ◽

pp. e047993

Author(s):

Nirosen Vijiaratnam ◽

Christine Girges ◽

Grace Auld ◽

Marisa Chau ◽

Kate Maclagan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Primary Outcome ◽

Phase 3 ◽

Double Blind ◽

Treatment Groups ◽

Link Type ◽

South Central ◽

Disease Modifying ◽

Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

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Diclofenac Sodium Gel in Patients with Primary Hand Osteoarthritis: A Randomized, Double-blind, Placebo-controlled Trial

The Journal of Rheumatology ◽

10.3899/jrheum.081316 ◽

2009 ◽

Vol 36 (9) ◽

pp. 1991-1999 ◽

Cited By ~ 78

Author(s):

ROY D. ALTMAN ◽

RENÉE-LILIANE DREISER ◽

CHESTER L. FISHER ◽

WALTER F. CHASE ◽

DONATUS S. DREHER ◽

...

Keyword(s):

Disease Activity ◽

Pain Intensity ◽

Primary Outcome ◽

Controlled Trial ◽

Diclofenac Sodium ◽

Global Rating ◽

Hand Osteoarthritis ◽

Dominant Hand ◽

Double Blind ◽

Secondary Outcomes

Objective.To measure the efficacy and safety of diclofenac sodium gel in patients with primary hand osteoarthritis (OA).Methods.In a randomized, double-blind, placebo-controlled trial, men and women aged ≥ 40 years diagnosed with primary OA in the dominant hand were randomly assigned to self-apply topical 1% diclofenac sodium gel (Voltaren® Gel) (n = 198) or vehicle (n = 187) to both hands 4 times daily for 8 weeks. Primary outcome measures included OA pain intensity (100-mm visual analog scale), total Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease activity at 4 and 6 weeks. Secondary outcomes included onset of efficacy in Weeks 1 and 2, durability of efficacy at 8 weeks, measures of disease activity in the dominant hand, pain intensity in the non-dominant hand, AUSCAN subindices, end of study rating of efficacy, and Osteoarthritis Research Society International response criteria.Results.Diclofenac sodium gel decreased pain intensity scores by 42%–45%, total AUSCAN scores by 35%–40%, and global rating of disease by 36%–40%. Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN, with a trend for global rating of disease activity. At Week 6, diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle. Secondary outcomes generally supported the primary outcomes. The most common treatment-related adverse event (AE) was application-site paresthesia. Most AE were mild. No cardiac events, gastrointestinal bleeding, or ulcers were reported.Conclusion.Topical diclofenac sodium gel was generally well tolerated and effective in primary hand OA. (NCT ID: NCT00171665)

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Efficacy of montelukast in the management of COVID-19: double blind randomized placebo controlled trial

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20214502 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1374

Author(s):

Vijay Kumar ◽

Avinash A. Ganapule ◽

Sushmita Supriya ◽

Divendu Bhushan ◽

Pallavi Lohani ◽

...

Keyword(s):

Mechanical Ventilation ◽

Primary Outcome ◽

Controlled Trial ◽

Severe Disease ◽

Final Analysis ◽

Standard Operating Procedure ◽

Double Blind ◽

Randomized Controlled ◽

Secondary Outcomes ◽

Double Blinded

Background: Objective of the study was to determine the efficacy of montelukast in reducing the severity of COVID-19 symptoms using a double blinded randomized controlled trial.Methods: Parallel, double-blinded randomized controlled trial (RCT) with placebo as comparison to montelukast. All patients above the age of 14 years both males and females, admitted with a diagnosis of mild or moderate COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period from 01 September 2020-31 January 2021) and excluding those having adverse reaction to montelukast or those not willing to participate, and pregnant and lactating females. Patients in the intervention arm were given tablet montelukast 10 mg OD HS from the day of admission for 10 days. The patients in the placebo group were given an identical appearing placebo at bedtime for 10 days from the day of admission. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with minor adjustments as per the treating team’s judgement. Primary outcome was progression of the disease to severe grade and secondary outcomes were discharge on or before day 10 from admission, admission to ICU, need for mechanical ventilation and in-hospital mortality.Results: A total of 94 patients were enrolled for the study. 90 patients, 45 in each arm were included in the final analysis. The baseline characteristics of the two arms including age, sex, comorbidities, severity at admission and treatment given apart from montelukast or placebo, were comparable with respect to these variables. This study did not find any improvement in primary outcome of progression to severe disease and secondary outcomes of intensive care unit (ICU) admission, mortality or need of mechanical ventilation, discharge on or by day 10 with the use of montelukast as compared to placebo in mild to moderate cases of COVID-19.Conclusions: There was no difference in primary or secondary outcomes with the use of Montelukast compared to placebo.

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Efficacy of Platelet-Rich Plasma and Plasma for Symptomatic Treatment of Knee Osteoarthritis: A Double-Blinded Placebo-Controlled Randomized Clinical Trial.

10.21203/rs.3.rs-514603/v1 ◽

2021 ◽

Author(s):

Murillo Dório ◽

Rosa Maria Rodrigues Pereira ◽

Alexandre Galeno Branco Luz ◽

Leticia Alle Deveza ◽

Ricardo Manoel Oliveira ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Primary Outcome ◽

Platelet Rich Plasma ◽

Controlled Trial ◽

Symptomatic Treatment ◽

Treatment Alternative ◽

Double Blind ◽

Secondary Outcomes ◽

Double Blinded ◽

And Function

Abstract Background: Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks. Methods: Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT. Results: At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/m2and mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain.Conclusions: PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain.Trial registration: ClinicalTrials.gov, NCT03138317, 03/05/2017.

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Stimulant Abuse in Burn Patients Is Associated With an Increased Use of Hospital Resources

Journal of Burn Care & Research ◽

10.1093/jbcr/iraa087 ◽

2020 ◽

Vol 41 (5) ◽

pp. 921-925

Author(s):

Ian F Hulsebos ◽

Christopher H Pham ◽

Zachary J Collier ◽

Mike Fang ◽

Sebastian Q Vrouwe ◽

...

Keyword(s):

Primary Outcome ◽

Surgical Intervention ◽

Inhalation Injury ◽

Burn Injuries ◽

Burn Patients ◽

Peripheral Vasculature ◽

Urine Toxicology ◽

Hospital Resources ◽

Hospital Days ◽

Surgical Operations

Abstract Stimulant (cocaine, methamphetamine, and amphetamine) abuse compromises the peripheral vasculature through endothelial injury. In combination with the physiologic derangements seen in burn injuries, patients abusing stimulants may have additional impairments in wound healing. A retrospective review from July 1, 2015 to July 1, 2018 was performed at an American Burn Association-verified burn center. Patients with positive urine toxicology results for stimulants (ST(+)), and those without (ST(−)), who sustained burn injuries were identified and matched by age and TBSA. The primary outcome was mortality, and secondary outcomes included total length of stay (LOS), and need-for-surgery (grafting). In total, 130 patients ST(+) and 133 ST(−) patients were identified. There were no significant differences in age (40.9 ± 13.5 vs 39.2 ± 23.7 years, P = 0.46), Inhalation Injury (12.3 vs 9.0%, P = 0.39), or nutritional status (prealbumin: 17.3 ± 6.1 vs 17.1 ± 12.7 mg/dl, P = 0.66; albumin: 3.5 ± 0.6 vs 3.6 ± 0.7 g/dl, P = 0.45). There were no differences in mortality (6.1 vs 4.5%, P = 0.55), intensive care unit LOS (9.3 ± 16.5 vs 10.2 ± 20.9 days, P = 0.81), wound infections (15.4 vs 23.9%, P = 0.07), or wound conversion (6.9 vs 3.0%, P = 0.14). ST(+) patients had a significantly longer LOS (15.0 ± 16.9 vs 10.7 ± 17.3 days, P = 0.04), greater tobacco use (56.9 vs 18.0%, P = 0.00001), and greater need for grafting (54.6 vs 33.1%, P = 0.0004). ST(+) patients require more hospital resources—surgical operations and hospital days—than ST(−) patients. The increased need for surgical intervention may partially explain the increase in hospital days, in addition to the observation that ST(+) patients had more complex disposition issues than ST(−) patients.

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Management of the Patient with Thermal Injuries

DeckerMed Surgery ◽

10.2310/surg.2142 ◽

2016 ◽

Author(s):

Michael J. Mosier ◽

Nicole S. Gibran

Keyword(s):

Carbon Monoxide ◽

Carbon Monoxide Poisoning ◽

Fluid Management ◽

Clinical Manifestations ◽

Injured Patient ◽

Inhalation Injury ◽

Burn Patients ◽

Burn Care ◽

Burn Resuscitation ◽

Burn Patient

Optimal care of the burn patient requires not only specialized equipment but also, more importantly, a team of dedicated surgeons, nurses, therapists, nutritionists, pharmacists, social workers, psychologists, and operating room staff. Burn care was one of the first specialties to adopt a multidisciplinary approach, and over the past 30 years, burn centers have decreased burn mortality by coordinating prehospital patient management, resuscitation methods, and surgical and critical care of patients with major burns. This review covers where to treat burn patients, fluid management, airway management, temperature regulation, airway control, nutrition, anemia, pain management, deep vein thrombosis prophylaxis, and putting it all together: an algorithmic approach to early care of the burn-injured patient. Figures show that the size of a burn can be estimated by means of the Rule of Nines, which assigns percentages of total body surface to the head, the extremities, and the front and back of the torso, the approach to the burn patient in the first 24 hours, and the approach to the burn patient during the second to fifth days after burn injury. Tables list American Burn Association criteria for burn injuries that warrant referral to a burn unit, criteria for outpatient management of burn patients, acute physiologic changes during burn resuscitation, acute biochemical and hematologic changes during burn resuscitation, measures of pulmonary function, mechanisms of pulmonary dysfunction and indications for mechanical ventilation, clinical manifestations of carbon monoxide poisoning, half-life of carbon monoxide–hemoglobin bonds with inhalation therapy, increased acute kidney injury in patients treated with hydroxocobalamin for suspected inhalation injury, clinical findings associated with specific inhaled products of combustion, bronchoscopic criteria used to grade inhalation injury, and formulas for estimating caloric needs in burn patients. This review contains 3 highly rendered figures, 12 tables, and 134 references

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Management of the Patient with Thermal Injuries

10.2310/7ccsp.2142 ◽

2016 ◽

Author(s):

Michael J. Mosier ◽

Nicole S. Gibran

Keyword(s):

Carbon Monoxide ◽

Carbon Monoxide Poisoning ◽

Fluid Management ◽

Clinical Manifestations ◽

Injured Patient ◽

Inhalation Injury ◽

Burn Patients ◽

Burn Care ◽

Burn Resuscitation ◽

Burn Patient

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Efficacy of Chlorhexidine Varnish for the Prevention of Adult Caries

Journal of Dental Research ◽

10.1177/0022034511424154 ◽

2011 ◽

Vol 91 (2) ◽

pp. 150-155 ◽

Cited By ~ 21

Author(s):

A.S. Papas ◽

W.M. Vollmer ◽

C.M. Gullion ◽

J. Bader ◽

R. Laws ◽

...

Keyword(s):

Primary Outcome ◽

Tooth Surface ◽

Placebo Control ◽

Double Blind ◽

Intention To Treat ◽

Significant Difference ◽

Registration Number ◽

Secondary Outcomes ◽

Study Participants ◽

To Receive

The Prevention of Adult Caries Study, an NIDCR-funded multicenter, double-blind, randomized clinical trial, enrolled 983 adults (aged 18-80 yrs) at high risk for developing caries (20 or more intact teeth and 2 or more lesions at screening) to test the efficacy of a chlorhexidine diacetate 10% weight per volume (w/v) dental coating (CHX). We excluded participants for whom the study treatment was contraindicated or whose health might affect outcomes or ability to complete the study. Participants were randomly assigned to receive either the CHX coating (n = 490) or a placebo control (n = 493). Coatings were applied weekly for 4 weeks and a fifth time 6 months later. The primary outcome (total net D1-2FS increment) was the sum of weighted counts of changes in tooth surface status over 13 months. We observed no significant difference between the two treatment arms in either the intention-to-treat or per-protocol analyses. Analysis of 3 protocol-specified secondary outcomes produced similar findings. This trial failed to find that 10% (w/v) chlorhexidine diacetate coating was superior to placebo coating for the prevention of new caries ( Clinicaltrials.gov registration number NCT00357877).

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Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218547 ◽

2020 ◽

pp. annrheumdis-2020-218547

Author(s):

Pascal Richette ◽

Augustin Latourte ◽

Jérémie Sellam ◽

Daniel Wendling ◽

Muriel Piperno ◽

...

Keyword(s):

Primary Outcome ◽

Controlled Study ◽

Hand Osteoarthritis ◽

Double Blind ◽

Osteoarthritis Pain ◽

Inflammatory Drugs ◽

The Mean ◽

Secondary Outcomes ◽

And Function ◽

To Receive

ObjectiveTo evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis.MethodsThis was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0–100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients’ and physicians’ global assessment and function scores.ResultsOf 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was −7.9 (SD 19.4) and −9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group.ConclusionTocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

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Efficacy of an Anti-Cellulite Herbal Emgel: A Randomized Clinical Trial

Pharmaceuticals ◽

10.3390/ph14070683 ◽

2021 ◽

Vol 14 (7) ◽

pp. 683

Author(s):

Ngamrayu Ngamdokmai ◽

Neti Waranuch ◽

Krongkarn Chootip ◽

Katechan Jampachaisri ◽

C. Norman Scholfield ◽

...

Keyword(s):

Primary Outcome ◽

Controlled Trial ◽

Subcutaneous Fat ◽

Volatile Oils ◽

Double Blind ◽

Severity Scores ◽

Secondary Outcomes ◽

Cutaneous Blood ◽

Time Point

Cellulite describes unsightly skin overlying subcutaneous fat around thighs and buttocks of post-pubescent females. A herbal ‘emgel’ containing volatile oils and extracts of A traditional Thai herbal compress was tested in a double-blind, placebo-controlled trial with 18 women aged 20–50 year with severe cellulite. Appearance of cellulite (primary outcome), thigh circumferences, skin firmness, and cutaneous blood flow (secondary outcomes) were assessed at baseline, 2, 4, 8 and 12 weeks with a 2-week follow-up. Herbal emgel applied onto the thigh skin twice daily reduced cellulite severity scores in every time point. The score was reduced from 13.4 ± 0.3 (baseline) to 12.1 ± 0.3 (week 2) and 9.9 ± 0.6 (week 12). All secondary outcomes improved with both placebo and herbal emgels suggesting that ingredients in the base-formulation might be responsible. Querying of participants, analysis of their diaries, and physical monthly inspections found no adverse events. The herbal emgel safely improved the appearance of cellulite, while the base emgel may play a role for other endpoints. Further studies on the active constituents and their mechanism of action are needed to further explore these factors.

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