Dried irradiated human amniotic membrane as a biological dressing for facial burns—A 7-year case series

Background

Facial burns are common and have a significant impact on patient function and psychosocial well being. Human amnion has been used for many years as a temporary biological wound dressing in the management of partial thickness burns. The observed advantages of human amnion treatment include pain relief, ease of use, prevention of infection and acceleration of wound healing.

Objective

This study evaluated our 7 years of working with dried irradiated human amnion in the treatment of facial burns.

Method

A review of patients, treated with dried human amnion for facial burns between 2001 and 2008. Demographic details collected included age, gender, total facial surface area burned, type of burn and cause of injury. The effectiveness of the treatment was determined by wound infection rate, frequency of dressing reapplication, healing time and resulting scarring.

Results

Thirty-three patients with superficial partial thickness burn were identified (25 males, 8 females). The average age of the patients was 16.5 years (range: 8 months to 64 years). The causes included scalding (n = 15), contact burning (n = 13) and flash burning (n = 5). The mean percent total facial surface area burned was 2.7% (range: 0.5–8.5%). None of the patients developed facial wound infections. Eighty-five percent (n = 28) of the patients needed a single application of the dried amnion. The average healing time was 5.4 days (range: 2–14 days). Thirteen patients (39%) had burns confined to the facial area, of which three were discharged and treated as outpatients. Long-term follow up showed two hypopigmented scars, one hyperpigmented scar and one hypertrophic scar.

Conclusion

Superficial partial thickness facial burns can be effectively treated with dried irradiated human amnion membrane.     

Modernized standards in burns management: A comparative study in Komfo Anokye Teaching Hospital,Kumasi, Ghana

Background

Management of burns patients before May 2009 was very difficult at the Komfo Anokye Teaching Hospital (KATH).

Aim

To compile burns patients’ information in the new Burns Intensive Care Unit (BICU), analyze it and draw comparisons to information from the old BICU at KATH.

Methods

This retrospective study involves data from May 2007 to April 2009 (Group 1 – old BICU) and May 2009 to April 2011 (Group 2 – new BICU). The parameters of burn patients recorded included: record of admission, gender, age, aetiology of injury, Total Burns Surface Area (TBSA), the patients’ treatment regime and record of discharge/death. This information was analyzed with SPSS version 18.0.

Results

The total number of patients in the study was 511; Group 1 constituted 47.36% (n = 242) patients; males (n = 307, 61%) outnumbering females (n = 204, 39%). The overall mean, median and interquartile range (IQR) ages of the patients were 12.4 ± 2; 9.5 and 18.0 years respectively. The main aetiology of burns in Group 1 was flame burns (n = 115, 47.5%) and for Group 2 was scald (n = 151, 56.1%). The median TBSA recorded for Groups 1 and 2 were 32% and 41% respectively. A mortality rate of 19.1% (n = 46) and 12.7% (n = 34) were recorded for Groups 1 and 2 respectively which was statistically significant (p < 0.05). We found no differences for age and TBSA (P = 0.7168 and P = 0.8020 respectively). A Chi Square analysis for gender and aetiology of burn revealed no significant difference between Groups 1 and 2. A risk factor analysis for mortality within the Groups (using multiple regression analysis) identified only aetiology of burn in Group 1 to be a factor (P = 0.044).

Conclusion

This comparative study reveals that a significant difference in mortality was recorded for both groups. The mortality difference does not appear to be due to socio-demographic features. This study may demonstrate that modernized and advanced equipment with the adequate personnel play an essential role in burn management in low income countries such as Ghana.     

The impact of laser Doppler imaging on the early decision-making process for surgical intervention in adults with indeterminate burns

Objective

We aimed to analyze whether laser Doppler imaging (LDI) can lead to earlier decision-making regarding the need for surgery in adults with indeterminate burns.

Methods

In a retrospective cohort study, we developed a prediction model for surgery in adults with indeterminate burns. Patient data (n = 101) from January 2007 to December 2009 were used for model development, and those (n = 40) from January 2010 to October 2010 for external validation.

Results

Between non-surgical and surgical groups, there were significant differences for mean age (p = 0.009), % total body surface area burn (p = 0.016), site of burn wound (p = 0.033), and mean perfusion units (PU) (p < 0.001). Multiple logistic regression showed that only the mean PU differed significantly between the groups. The area under the curve (AUC) of the equation derived from multiple logistic regression was 0.938, which did not differ from that of the mean PU alone (0.931; p = 0.453). Using a cut-off point of 154.7PU, the sensitivity of LDI was 78.3% and the specificity was 92.7%. This cut-off point also yielded a sensitivity of 77.8% and specificity of 95.5% in the external validation dataset.

Conclusion

LDI can help make a decision for surgery in the early stages of care for adults with indeterminate burns.     

Developing a burn injury severity score (BISS): Adding age and total body surface area burned to the injury severity score (ISS) improves mortality concordance

Background

There is limited research validating the injury severity score (ISS) in burns. We examined the concordance of ISS with burn mortality. We hypothesized that combining age and total body surface area (TBSA) burned to the ISS gives a more accurate mortality risk estimate.

Methods

Data from the Royal Perth Hospital Trauma Registry and the Royal Perth Hospital Burns Minimum Data Set were linked. Area under the receiver operating characteristic curve (AUC) measured concordance of ISS with mortality. Using logistic regression models with death as the dependent variable we developed a burn-specific injury severity score (BISS).

Results

There were 1344 burns with 24 (1.8%) deaths, median TBSA 5% (IQR 2–10), and median age 36 years (IQR 23–50). The results show ISS is a good predictor of death for burns when ISS ≤ 15 (OR 1.29, p = 0.02), but not for ISS > 15 (ISS 16–24: OR 1.09, p = 0.81; ISS 25–49: OR 0.81, p = 0.19). Comparing the AUCs adjusted for age, gender and cause, ISS of 84% (95% CI 82–85%) and BISS of 95% (95% CI 92–98%), demonstrated superior performance of BISS as a mortality predictor for burns.

Conclusion

ISS is a poor predictor of death in severe burns. The BISS combines ISS with age and TBSA and performs significantly better than the ISS.     

Clinical utility of fungal screening assays in adults with severe burns

Background

Fungal wound infection is a leading cause of burn wound infections, and diagnosis is often delayed as it conventionally requires culture and histopathology. Fungal screening assays have sped diagnosis of invasive fungal infections in other populations. Few studies have evaluated the performance of fungal screening assays outside of the hematologic malignancy and hematopoietic stem cell transplant populations.

Methods

We performed a three year retrospective analysis of all fungal screening assays in burn patients in the ICU between 2008 and 2011. The primary goal was to evaluate the correlation between the two available fungal screening assays, (1 → 3)-β-d-glucan (BG) and galactomannan (GM) assay, and fungal wound colonization (FWC) and infection (FWI). We also evaluated previously hypothesized causes of false positives and their associations with false positives in the burn population.

Results

We identified 53 patients [median 29% total body surface area burned (TBSA), IQR 17–51] with BG or GM serological tests available, of which 15 had a FWI or FWC. FWC/FWI was associated with higher TBSA (p = 0.02). BG and GM correlated with TBSA (BG 0.57, p < 0.01; GM 0.35, p = 0.02), but neither assay was associated with FWI/FWC or species of fungus involved when FWI/FWC was diagnosed.

Conclusions

Positive BG and GM fungal screening assays are not associated with FWI/FWC, or with species of fungus when FWC/FWI is present. BG false positives are common and associated with higher TBSA burns.     

Time course of CD marker expression in patients with burns and its prognostic value

Introduction

Due to immune suppression sepsis has remained the leading cause of mortality after burns. CD marker expression in circulating blood has not been fully examined in humans. The aim of our study was to asses CD marker expression after burns and to compare it between survivors and non-survivors.

Patients and methods

Blood samples from all patients (n = 35) receiving intensive care treatment with more than 20% burned surface area were collected on admission and 5 consecutive days thereafter. Expressions of CD11a, CD11b, CD18, CD49d, CD97 and CD14 were measured on granulocytes, lymphocytes and monocytes.

Results

Expressions of granulocytes CD11a (days 1–2), CD18 (day 1), lymphocytes CD11a (days 1–5), CD11b (days 2–4), CD18 (days 1–6), CD49d (days 1–6), CD97 (day 1), monocytes CD11a (days 1–6), CD11b (day 2 and 5–6), CD18 (days 1–6), CD49d (days 1–6), CD97 (days 1–2), and CD14 (days 4–6) were significantly lower in patients than in healthy controls.Expressions of granulocyte CD11a (days 3–6), lymphocytes CD11a (days 3–6), CD11b (days 4–6), CD18 (days 4–6), monocyte CD97 (days 3–6) were significantly higher in survivors (n = 20) than in non-survivors (n = 15).

Conclusion

These results suggest that burns is associated with immunosuppression and overwhelming anti-inflammatory processes may be signs of bad prognosis.     

Procalcitonin in the Burn Unit and the Diagnosis of Infection

Objective

To determine the usefulness of procalcitonin (PCT) in decision-making when faced with suspected infection in patients with extensive burns.

Study

Retrospective, observational follow-up study.

Institution

Burn Unit of the Complexo Hospitalario Universitario A Coruña (CHUAC), Spain.

Patients and method

We included all patients admitted to the Unit from June 2011 to March 2012 with ≥20% total body surface area burned or ≥10% full-thickness body surface area burned with suspected infection (17 patients with 34 events of suspected infection).

Results

The infections were confirmed in 16/34 episodes (47.1%), and documented in 44.1% (n = 15). There were no statistically significant differences in the PCT figures at the time the infection was suspected between the cases with confirmed and unconfirmed infection (p = 0.682). The PCT values showed no discriminative value for differentiating patients with SIRS from those with sepsis, severe sepsis and septic shock (area under ROC curve (AUC) = 0.546; 95% CI: 0.326–0.766). No significant correlation was found between SOFA and PCT, although there were differences in the PCT values in the patients who had tissue hypoperfusion.

Conclusion

Results show that PCT is not a precise indicator of sepsis at the time of diagnosis. A correlation between PCT levels and hypoperfusion was observed.     

Time course of pro- and anti-inflammatory cytokine levels in patients with burns—Prognostic value of interleukin-10

Introduction

Trends and the prognostic value of cytokine responses to severe burns have not been fully examined in humans. Therefore, the aim of this study was to determine the time course and prognostic value of pro- and anti-inflammatory cytokines in the immediate post-burn period.

Patients and methods

Blood samples were taken for measuring IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α concentrations from patients with more than 20% burned surface area on admission and on 5 consecutive days. Development of sepsis was assessed using standard criteria twice a day.

Results

IL-12p70 remained under assay detection levels in the study period. IL-1β and TNF-α could be detected in stimulated blood samples with higher levels in survivors (n = 21). IL-6 on days 4–5 and IL-8 on days 4–6 in non-stimulated plasma showed significant elevation in non-survivors (n = 18) whereas in stimulated blood its levels did not differ significantly. IL-10 levels were significantly higher in non-survivors during the study period in non-stimulated, and except day 6 in stimulated blood. Using the cut-off level of 14 pg ml⁻¹ for IL-10 predicted ICU mortality with 85.4% sensitivity and 84.2% specificity on admission.

Conclusion

Early anti-inflammatory excess had a bad prognosis for patients suffering from severe burns.     

Staphylococcus aureus bacteremia after thermal injury: The clinical impact of methicillin resistance

Objective

To evaluate the impact of methicillin resistance in Staphylococcus aureus bacteremia (SAB) on mortality and length of stay in burn patients.

Design

Retrospective cohort study.

Setting

A 750-bed tertiary care university hospital in Cologne, Germany.

Patients

Patients registered in the database of the burn intensive care unit (BICU) between 1989 and 2009 with complete data sets (n = 1688).

Results

Over the 21-year study period, 74 patients with SAB were identified; 33 patients had methicillin-resistant S. aureus (MRSA) and 41 methicillin-susceptible S. aureus (MSSA). Comparing the MRSA with the MSSA population the following parameters were significantly different in the univariate analysis: BMI (27.2 kg/m² vs. 23.6 kg/m²; P = 0.05), extent of deep partial thickness burns (17.8% vs. 9.0% of total body surface area; P = 0.007), antibiotic requirement on admission (45.5% vs. 22.0%; P = 0.046), median length of hospitalization prior SAB (24 days vs. 7 days; P < 0.001), packed red blood cells administration (47.6 units vs. 26.1 units; P = 0.003), intubation requirement (100% vs. 80.5%; P = 0.007), intubation period (43.5 days vs. 26.8 days; P = 0.008), catecholamine requirement (90.9% vs. 61.0%; P = 0.004), sepsis (60.6% vs. 34.1%; P = 0.035) and organ failures (81.8% vs. 39.0%; P < 0.001). Regarding outcome parameters, methicillin resistance was not significantly related with mortality (adjusted OR 1.55, 95% CI 0.56–4.28; P = 0.40) and length of BICU stay after SAB (Kaplan–Meier analysis log-rank test P = 0.32; Cox's proportional hazards regression HR 1.22, 95% CI 0.65–2.27, P = 0.535) in the univariate and multivariate analyses.

Conclusion

Our data suggest that methicillin resistance is not associated with significant increases in mortality and length of BICU stay among burn patients with SAB.     

A systematic review of the literature to support an evidence-based Precepting Program

Aim

To provide a systematic review of the literature regarding development of an evidence-based Precepting Program for nurses transitioning to burn specialty practice.

Background

Burned patients are admitted to specialty Burn Centers where highly complex nursing care is provided. Successful orientation and integration into such a specialized work environment is a fundamental component of a nurse's ability to provide safe and holistic patient care.

Design

A systematic review of the literature was performed for the period 1995–2011 using electronic databases within PUBMED and Ovid search engines.

Data sources

Databases included Medline, CINHAL, ProQuest for Dissertations and Thesis, and Cochran Collaboration using key search terms: preceptor, preceptee, preceptorship, precept*, nurs*, critical care, personality types, competency-based education, and learning styles.

Review methods

Nurses graded the level and quality of evidence of the included articles using a modified 7-level rating system and the Johns Hopkins Nursing Quality of Evidence Appraisal during journal-club meetings.

Results

A total of 43 articles related to competency (n = 8), knowledge acquisition and personality characteristics (n = 8), learning style (n = 5), preceptor development (n = 7), and Precepting Programs (n = 14).

Conclusions

A significant clinical gap existed between the scientific evidence and actual precepting practice of experienced nurses at the Burn Center. Based on this extensive review of the literature, it was determined that a sufficient evidence base existed for development of an evidence-based Precepting Program.     

Comparison of Oncologic Outcomes for Open and Laparoscopic Nephroureterectomy: A Multi-Institutional Analysis of 1249 Cases

Background

Data regarding the oncologic efficacy of laparoscopic nephroureterectomy (LNU) compared to open nephroureterectomy (ONU) are scarce.

Objective

We compared recurrence and cause-specific mortality rates of ONU and LNU.

Design, setting, and participants

Thirteen centers from three continents contributed data on 1249 patients with nonmetastatic upper tract urothelial carcinoma (UTUC).

Measurements

Univariable and multivariable survival models tested the effect of procedure type (ONU [n = 979] vs LNU [n = 270]) on cancer recurrence and cancer-specific mortality. Covariables consisted of institution, age, Eastern Cooperative Oncology Group (ECOG) performance status score, pT stage, pN stage, tumor grade, lymphovascular invasion, tumor location, concomitant carcinoma in situ, ureteral cuff management, previous urothelial bladder cancer, and previous endoscopic treatment.

Results and limitations

Median follow-up for censored cases was 49 mo (mean: 62). Relative to ONU, LNU patients had more favorable pathologic stages (pT0/Ta/Tis: 38.1% vs 20.8%, p < 0.001) and less lymphovascular invasion (14.8% vs 21.3%, p = 0.02) and less frequently had tumors located in the ureter (64.5 vs 71.1%, p = 0.04). In univariable recurrence and cancer-specific mortality models, ONU was associated with higher cancer recurrence and mortality rates compared to LNU (hazard ratio [HR]: 2.1 [p < 0.001] and 2.0 [p = 0.008], respectively). After adjustment for all covariates, ONU and LNU had no residual effect on cancer recurrence and mortality (p = 0.1 for both).

Conclusions

Short-term oncologic data on LNU are comparable to ONU. Since LNU was selectively performed in favorable-risk patients, we cannot state with certainty that ONU and LNU have the same oncologic efficacy in poor-risk patients. Long-term follow-up data and morbidity data are necessary before LNU can be considered as the standard of care in patients with muscle-invasive or high-grade UTUC.     

Interleukin-8 predicts 60-day mortality in premature infants with necrotizing enterocolitis

Objective

The purpose of this study was to evaluate the predictiveness of circulating interleukin (IL)-8 for 60-day mortality in premature infants with necrotizing enterocolitis (NEC).

Background

NEC affects up to 5% of premature infants and remains a leading cause of mortality among neonates.

Methods

A total of 113 infants with surgically (n = 50) or medically (n = 63) treated NEC were retrospectively analyzed. Laboratory parameters including serum IL-8 were assessed at the diagnosis of NEC and during the preoperative workup.

Results

The 60-day mortality was 19% (22/113), 10% (6/63) in medical and 33% (16/50) in surgical NEC. IL-8 levels significantly correlated with 60-day mortality (odds ratio: 1.38; CI 1.14–1.67; p = 0.001). Median IL-8 levels at diagnosis were significantly higher in neonates who were later treated surgically (median = 2625 pg/ml; range: 27–7500) compared with those treated medically (median = 156 pg/ml; range: 5–7500; p < 0.001). The AUC to discriminate between medical and surgical NEC was 0.82 (CI, 0.74–0.90), and an exploratory IL-8 cutoff point could be established at 1783 pg/ml (sensitivity of 90.5%; specificity of 59.2%).

Conclusions

Our findings that serum IL-8 (i) correlates directly with 60-day mortality and (ii) differs significantly between medically and surgically treated infants may change the process of therapeutic decision making in NEC.     

Hypoalbuminemia in the first 24 h of admission is associated with organ dysfunction in burned patients

Objective

Hypoalbuminemia is a common finding in burned patients, but its association with increased morbidity and mortality has not been well established. We assessed whether hypoalbuminemia in the first 24 h of admission is associated with organ dysfunction in patients with severe burns.

Methods

For a two year period (2008–2009), we reviewed the records of burn adult patients with a total body surface area 20% admitted in our unit within the first 24 h of injury. A multiple linear regression analysis was conducted to assess hypoalbuminemia as an independent predictor of organ dysfunction.

Results

56 subjects were analyzed. Multiple linear regression analysis showed that hypoalbuminemia in the first 24 h of admission was an independent predictor of organ dysfunction. Serum albumin concentration ≤30 g/L was associated with a two-fold increase in organ dysfunction [SOFA scores at day 0 (p = 0.005), day 1 (p = 0.005) and first week mean values (p = 0.004)], but not with mortality (p = 0.061).

Conclusion

Hypoalbuminemia is associated with organ dysfunction in burned patients. Unlike unmodifiable predictors such as age, burn surface and inhalation burn, correction of hypoalbuminemia might represent a goal for a future trial in burn patients.     

The correlation between burn mortality rates from fire and flame and economic status of countries

Introduction

Over 95% of burn deaths occur in low- and middle-income countries globally. However, the association between burn mortality rates and economic health has not been evaluated for individual countries. This study seeks to answer the question, how strong is the correlation between burn mortality and national indices of economic strength?

Methods

A retrospective review was performed for 189 countries during 2008–2010 using economic data from the World Bank as well as mortality data from the World Health Organization (WHO). Countries were categorized into four groups based on income level according to stratification by the World Bank: low income, lower middle income, upper middle income, and high income. The Pearson correlation coefficient was used to estimate presence and strength of association among death rates, Gini coefficient (measure of inequality of distribution of wealth), gross domestic product (GDP) per capita, and gross national index (GNI) per capita.

Results

Statistically significant associations (p < 0.05) were found between burn mortality and GDP per capita (r = −0.26), GNI per capita (r = −0.36), and Gini (r = +0.17).

Conclusions

A nation's income level is negatively correlated with burn mortality; the lower the income level, the higher the burn mortality rates. The degree to which income within a country is equitably or inequitably distributed also correlates with burn mortality.

Significance

Both governmental and non-governmental organizations need to focus on preventing burns in low-income countries, as well as in other countries in which there is marked disparity of income.     

Cologne burn centre experience with assault burn injuries

Objective

To evaluate demographic and socioeconomic factors associated with assault burn injuries.

Background

Assault by burning demonstrates a rare but severe public health issue and accounts for unique injury characteristics in the burn intensive care unit (BICU).

Methods

We conducted a retrospective cohort study involving patients with thermal injuries admitted to the BICU of a university hospital. The patient cohort was divided into two groups (ABI group: patients with assault burns, n = 41; Control group: population of all other burned patients admitted to the BICU, n = 1202). Bivariate and multivariate analyses including demographic and socioeconomic data were used to identify factors associated with assault burns.

Results

Forty-one assault-related burn victims were identified in the study period. This represents 3.3% of all significant burns admitted. Comparing battery victims with the control population, assault patients were more likely to be young (mean age 36.2 years vs. 42.2 years) and immigrants (41.5% vs. 15.1%). Furthermore, marital status (65.9% vs. 40.8% singles), employment status (36.6% vs. 9.7% unemployed) and insurance status (41.5% vs. 12.3% social insurance) were significantly different in the bivariate analysis. Logistic regression evaluation identified three variables that were independently associated with assault burns: younger age (≤25 years) (odds ratio, 2.54 [95% confidence interval, 1.29–5.02]; p = 0.007), ethnic minority (odds ratio, 3.71 [95% confidence interval, 1.91–7.20]; p < 0.001) and unemployment (odds ratio, 4.02 [95% confidence interval, 2.03–7.97]; p < 0.001).

Conclusions

The high incidence of youngsters, unemployment and the great proportion of immigrants in victims of assault might provide several opportunities for community-based psychosocial and occupational programs. A multidisciplinary approach targeting issues specific to the violent nature of the injury and the socioeconomic background of the victims may be of benefit to improve their perspectives for rehabilitation.     

A 10-year experience with major burns from a non-burn intensive care unit

Objective

The aim of this study was to review clinical data and outcomes of patients with burns in a Mexican non-burn intensive care unit (ICU).

Methods

We did a retrospective analysis of our single-centre database of burn patients admitted to the ICU in the Hospital Civil Fray Antonio Alcalde (University Hospital). The sample was divided for analysis into two groups according to the outcome ‘death’ or ‘discharge’ from ICU.

Results

Overall mortality was 58.2%, without a decreasing trend in mortality rates through the years. We identified the presence of third-degree burns (odds ratio (OR) 1.5, p = 0.003), and >49% total burned surface area (TBSA; OR 3.3, p ≤ 0.001) was associated with mortality. Mean age was higher in deceased patients (38.2 years vs. 31.3 years, p = 0.003) as was the TBSA (62.8% vs. 36.4%, p ≤ 0.001). At multivariate analysis, inhalation injury was not associated with increased mortality, but it was with more mechanical ventilation days. Early surgical debridement/cleansing was performed in most patients; however, the mean of the procedures was 1.7 per patient in both groups.

Conclusion

We identified significant factors associated with mortality. These variables and prognosis from non-burn ICUs differ broadly compared with burn intensive care units (BICUs); thus, more structured, multidisciplinary and specialised treatment strategies are still needed.     

Epidemiological analysis of burn patients in East Bulgaria

Objective

The purpose of the study was to identify the basic epidemiological characteristics of burn patients in East Bulgaria, as well as to analyze trends in burns in the region over the last decade.

Methods

Retrospective data of burn patients treated at Military Hospital-Varna, in the period January 2002–December 2011, was reviewed and statistically interpreted in terms of patients and burn demographics; etiology; place of incidents; hospital stay and mortality. Trends were observed for the entire period and comparative analyses of patients’ data were made between two periods: first – 2002–2006 and second 2007–2011.

Results

A total of 2627 burn patients, median age 41 years (IQR 9–61) were admitted to our burn unit. For the entire period the most affected age groups were ≤4 years (21.6%) and ≥65 years (21.1%). Hospitalized patients increased in the second period (n = 1701) compared to the first one (n = 926), while the size of total burn surface area decreased (first period – 9.8% vs. second period – 10.6%). Scald (51%) and flame (23.8%) were the most frequent aetiological agents for both periods. Work related burns reduced in the second period (9.4% vs. 4.9%), while home burns (90.6 vs. 95.1%) increased. Hospital stay declined from 17days (2002–2006) to 7days (2007–2011), whereas mortality rate slightly increased (first period – 2.3% vs. second period – 3.6%).

Conclusion

Burns remain a significant health problem in Bulgaria. The future preventive actions should take into account the observed changes in burn demographics and target the most vulnerable groups.     

Disease Control Outcomes from Analysis of Pooled Individual Patient Data from Five Comparative Randomised Clinical Trials of Degarelix Versus Luteinising Hormone-releasing Hormone Agonists

Background

Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes.

Objective

To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.

Design, setting, and participants

Data were pooled from five prospective, phase 3 or 3b randomised trials (n = 1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n = 467) or 12 mo (n = 1458) of treatment.

Intervention

Men were randomised to receive degarelix (n = 1266), leuprolide (n = 201), or goserelin (n = 458).

Outcome measurements and statistical analysis

Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events.

Results and limitations

Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p = 0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p = 0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p = 0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p = 0.006). In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group.

Conclusions

These data indicate clinical benefits with degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists.     

A Randomized Double-blind Placebo-controlled Phase 2 Dose-ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

Background

Botulinum toxin treatment has been investigated as a minimally invasive alternative to oral medications in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH).

Objective

To explore the efficacy of onabotulinumtoxinA 100 U, 200 U, and 300 U versus placebo in men with LUTS/BPH in a phase 2 dose-ranging study.

Design, setting, and participants

A multicenter double-blind randomized, placebo-controlled 72-wk study enrolled men ≥50 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥12, total prostate volume (TPV) 30–100 ml, and maximum flow rate (Q_max) 5–15 ml/s.

Intervention

Single transperineal (n = 63) or transrectal (n = 311) administration of placebo (n = 94) or onabotulinumtoxinA 100 U (n = 95), 200 U (n = 94), or 300 U (n = 97) into the prostate transition zone.

Outcome measurements and statistical analysis

The primary efficacy end point was a change from baseline in IPSS at week 12. Secondary end points were Q_max, TPV, and transition zone volume (TZV). Analysis of covariance and the Cochran-Mantel-Haenszel method assessed the efficacy and proportion of IPSS responders. Adverse events (AEs) were assessed.

Results and limitations

Significant improvements from baseline in IPSS, Q_max, TPV, and TZV were observed for all groups, including placebo, at week 12 (p < 0.001), with no significant differences between onabotulinumtoxinA and placebo. However, in an exploratory post hoc analysis, a significant reduction in IPSS versus placebo was observed with onabotulinumtoxinA 200 U in prior α-blocker users (n = 180) at week 12. AEs were comparable across all groups.

Conclusions

Reductions in LUTS/BPH symptoms were seen in all groups, including placebo, with no significant between-group differences owing to a large placebo effect from the injectable therapy. The findings from the post hoc analysis in men previously treated with α-blockers will be further explored in an appropriately designed study.

Trial registration

http://www.Clinical Trials.gov; NCT00284518.     

Prognostic factors for amputation in severe burn patients

Introduction

Amputation is a rare procedure among burned patients. However, it has significant physical and psychological consequences which impact quality of life.

Objective

To study the incidence, etiology and prognostic factors associated with amputation among burned patients in Chile.

Methods

Cohort study of patients admitted to the Reference Burn Center of Chile from 2006 to 2011. Association of demographic, event and injury variables with the likelihood of amputation were evaluated by using multivariable analysis.

Results

Amputation incidence was 5.8% in 1090 admitted patients. Male amputee patients were significantly more frequent (p = 0.01), with more electrical and high voltage burns (p < 0.01) and had greater frequency of impaired consciousness (p = 0.03). Multivariable analysis identified electrical burns (OR 13.7; 95% CI 6.7–28.1) and impaired consciousness (OR 2.8; 95% CI 1.4–5.7) as prognostic factors for amputation.

Conclusion

Amputation is a low incidence procedure among burned patients. Patients who underwent amputations are frequently at working age. Patients with high-voltage electrical burns and impaired consciousness are more likely to undergo amputation. Since these are highly incapacitating injuries, it is very important to implement preventive measures.