The impact of necrotizing soft tissue infections on the lives of survivors: a qualitative study.

PURPOSE: Necrotizing soft tissue infections (NSTI) are potentially lethal infections marked by local tissue destruction and systemic sepsis, which require aggressive treatment. Survivors often face a long recovery trajectory. This study was initiated to increase understanding of the long-term impact of NSTI on health related quality of life (HRQoL), and how care may be improved. METHODS: Thematic analysis was applied to qualitative data from 25 NSTI-survivors obtained through two focus groups (n = 14) and semi-structured interviews (n = 11). RESULTS: The median age of the participants was 49 years, 14 were female. The median time since diagnosis was 5 years. Initial misdiagnosis was common, causing delay to treatment. Survivors experienced long-term physical consequences (scarring, cognitive impairment, fatigue, sleeping problems, recurrent infections), psychological consequences (traumatic stress symptoms, fear of relapse, adjusting to an altered appearance, sexual issues) and social and relational consequences (changes in social contacts, a lack of understanding). The disease also had a major psychological impact on family members, as well as major financial impact in some. There was a strong desire to reflect on 'mistakes' in case of initial misdiagnosis. To improve care, patient and family centered care, smooth transitions after discharge, and the availability of understandable information were deemed important. CONCLUSION: This study reveals that NSTI have a large impact on physical and psychosocial wellbeing of survivors and their relatives. Except for a few differences (misdiagnosis, fear for re-infection and actual re-infection), the patient experience of patients with NSTI is largely similar to those of burn survivors. Thus, questionnaires to assess HRQoL in burn survivors may be used in future NSTI studies.

Short-term and long-term increased mortality in elderly patients with burn injury: a national longitudinal cohort study.

BACKGROUND: The population of elderly patients with burn injuries is growing. Insight into long-term mortality rates of elderly after burn injury and predictors affecting outcome is limited. This study aimed to provide this information. METHODS: A multicentre observational retrospective cohort study was conducted in all three Dutch burn centres. Patients aged ≥65 years, admitted with burn injuries between 2009 and 2018, were included. Data were retrieved from electronic patient records and the Dutch Burn Repository R3. Mortality rates and standardized mortality ratios (SMRs) were calculated. Multivariable logistic regression was used to assess predictors for in-hospital mortality and mortality after discharge at 1 year and five-year. Survival analysis was used to assess predictors of five-year mortality. RESULTS: In total, 682/771 admitted patients were discharged. One-year and five-year mortality rates were 8.1 and 23.4%. The SMRs were 1.9(95%CI 1.5-2.5) and 1.4(95%CI 1.2-1.6), respectively. The SMRs were highest in patients aged 75-80 years at 1 year (SMRs 2.7, 95%CI 1.82-3.87) and five-year in patients aged 65-74 years (SMRs 10.1, 95%CI 7.7-13.0). Independent predictors for mortality at 1 year after discharge were higher age (OR 1.1, 95%CI 1.0-1.1), severe comorbidity, (ASA-score ≥ 3) (OR 4.8, 95%CI 2.3-9.7), and a non-home discharge location (OR 2.0, 95%CI 1.1-3.8). The relative risk of dying up to five-year was increased by age (HR 1.1, 95%CI 1.0-1.1), severe comorbidity (HR 2.3, 95%CI 1.6-3.5), and non-home discharge location (HR 2.1, 95%CI 1.4-3.2). CONCLUSION: Long-term mortality until five-year after burn injury was higher than the age and sex-matched general Dutch population, and predicted by higher age, severe comorbidity, and a non-home discharge destination. Next to pre-injury characteristics, potential long-lasting systemic consequences on biological mechanisms following burn injuries probably play a role in increased mortality. Decreased health status makes patients more prone to burn injuries, leading to early death.

Short- and Long-term Outcomes of an Acellular Dermal Substitute versus Standard of Care in Burns and Reconstructions: A Phase I/II Intrapatient Randomized Controlled Trial.

OBJECTIVE: Dermal substitutes promote dermal regeneration and improve scar quality, but knowledge gaps remain regarding their efficacy and indications for use. The authors investigated the safety and short- and long-term efficacy of an acellular dermal substitute in patients with full-thickness wounds. METHODS: This intrapatient randomized controlled, open-label, phase I (safety) and phase II (efficacy) study compared treatment with Novomaix (Matricel GmbH), a dermal collagen/elastin-based scaffold, with split-thickness skin graft (STSG) only. The primary safety outcome was graft take at 5 to 7 days postsurgery. Postsurgical scar quality was assessed by measuring elasticity, color, and scores on the Patient and Observer Scar Assessment Scale at 3 months, 12 months, and 6 years. RESULTS: Twenty-five patients were included, of which 24 received treatment allocation. Graft take and wound healing were statistically significantly lower/delayed in the dermal matrix group compared with STSG alone (P < .004). Serious adverse events were delayed epithelialization in four dermal matrix and three STSG study areas. At 12 months postsurgery, skin extension (P = .034) and elasticity (P = .036) were better for the dermal matrix group compared with the group receiving STSG alone. Other scar quality parameters at 12 months and 6 years did not differ between treatment arms. CONCLUSIONS: The dermal substitute was a safe treatment modality for full-thickness wounds. Compared with STSG alone, time to wound healing was slightly increased. Nevertheless, scar quality at 12 months seemed somewhat improved in the wounds treated with the dermal substitute, indicative of enhanced scar maturation. In the long term, final scar quality was similar for both treatment modalities.

Hydrosurgical and conventional debridement of burns: randomized clinical trial.

BACKGROUND: Tangential excision of burned tissue followed by skin grafting is the cornerstone of burn surgery. Hydrosurgery has become popular for tangential excision, with the hypothesis that enhanced preservation of vital dermal tissue reduces scarring. The aim of this trial was to compare scar quality after hydrosurgical versus conventional debridement before split-skin grafting. METHODS: A double-blind randomized within-patient multicentre controlled trial was conducted in patients with burns that required split-skin grafting. One wound area was randomized to hydrosurgical debridement and the other to Weck knife debridement. The primary outcome was scar quality at 12 months, assessed with the observer part of the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes included complications, scar quality, colour, pliability, and histological dermal preservation. RESULTS: Some 137 patients were randomized. At 12 months, scars of the hydrosurgical debrided wounds had a lower POSAS observer total item score (mean 2.42 (95 per cent c.i. 2.26 to 2.59) versus 2.54 (95 per cent c.i. 2.36 to 2.72; P = 0.023)) and overall opinion score (mean 3.08 (95 per cent c.i. 2.88 to 3.28) versus 3.30 (95 per cent c.i. 3.09-3.51); P = 0.006). Patient-reported scar quality and pliability measurements were significantly better for the hydrosurgically debrided wounds. Complication rates did not differ between both treatments. Histologically, significantly more dermis was preserved with hydrosurgery (P < 0.001). CONCLUSION: One year after surgery scar quality and pliability was better for hydrosurgically debrided burns, probably owing to enhanced histological preservation of dermis. REGISTRATION NUMBER: Trial NL6085 (NTR6232 (http://www.trialregister.nl)).

Scar formation from the perspective of complexity science: a new look at the biological system as a whole.

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals.

The Skin-Sparing Debridement Technique in Necrotizing Soft-Tissue Infections: A Systematic Review.

BACKGROUND: Skin-sparing debridement (SSd) was introduced as an alternative to en bloc debridement (EBd) to decrease morbidity caused by scars in patients surviving Necrotizing soft-tissue infections (NSTI). An overview of potential advantages and disadvantages is needed. The aim of this review was to assess (1) whether SSd is noninferior to EBd regarding general outcomes, that is, mortality, length of stay (LOS), complications, and (2) if SSd does indeed result in decreased skin defects. METHODS: A systematic literature search was performed according to the PRISMA guidelines. All human studies describing patients treated with SSd were included, when at least of evidence level consecutive case series. Studies describing up to 20 patients were pooled to improve readability and prevent overemphasis of findings from single small studies. RESULTS: Ten studies, one cohort study and nine case series, all classified as poor based on Chambers criteria for case series, were included. Compared to patients treated with EBd, patients treated with SSd had no increased mortality rate, LOS or complication rate. SSd-treated patients had a high rate (75%) of total delayed primary closure (DPC) in the pooled case series. CONCLUSION: The current available evidence is of insufficient quality to conclude whether SSd is noninferior to EBd for all assessed outcomes. There are suggestions that SSd may result in a decreased need for skin transplants, which could potentially improve the (health related) quality of life in survivors. Experienced surgical teams could cautiously implement SSd under close monitoring, ideally with uniform outcome registry.

Scar quality in children with burns 5-7 years after injury: A cross-sectional multicentre study.

Long-term scar formation is an important adverse consequence in children with burns, however, information regarding scar quality in the long-term is lacking. Therefore, we evaluated scar quality and its predictors in children with burns 5-7 years after injury. Parents of children with mild/intermediate burns (≤10% total body surface area burned), and of children with severe burns (>10% burned) completed the patient scale of the Patient and Observer Scar Assessment Scale (POSAS 2.0) for their children's-in their opinion-worst scar 5-7 years post-burn. Outcomes and predictive factors of scar quality were studied, and, for children with severe burns, POSAS parent scores were compared with observer scores. We included 103 children with mild/intermediate burns and 28 with severe burns (response rate: 51%). Most children (87%) had scars that differed from normal skin, with most differences reported for colour, and least for pain. Except for colour, children with severe burns had significantly higher scores (difference 0-2 points) on all scar characteristics (representing poorer scar quality) compared with children with mild/intermediate burns. Parent POSAS scores were on average 2.0-2.6 points higher compared to observer scores. Number of surgeries predicted both the mean POSAS and the mean overall opinion of a scar. In conclusion, 5-7 years post-burn, the scar of the majority of children differed from normal skin, especially on the characteristic colour. The uncovered insights are useful in counselling of children and their parents on expectations of the final outcome of their (children's) scar(s), and help in further targeting scar prevention strategies for the individual child.

Unmet information needs of men with breast cancer and health professionals.

OBJECTIVE: Male breast cancer (MBC) is rare. Information about breast cancer is usually designed for female patients. However, in males this disease and some side effects differ from its female counterpart. Therefore, there is a need for male-specific information. The aim was to assess unmet information needs of (a) MBC patients and (b) health professionals. METHODS: Dutch MBC patients (diagnosed between 2011 and 2016 in 21 hospitals), patient advocates and partners were invited to participate in focus groups and/or complete a paper-based questionnaire on information needs. In addition, an online questionnaire on information needs was sent to health professionals involved in MBC patient care. RESULTS: In three focus groups with MBC patients (N = 12) and partners (N = 2) the following unmet information themes were identified: patients' experiences/photographs, symptoms, (delay of) diagnosis, treatments, side effects, follow-up, psychological impact/coping, genetics and family, research and raising awareness. 77 of 107 MBC patients (72%) completed the questionnaire: most patients lacked information about acute (65%) or late (56%) side effects, particularly sexual side effects. Among health professionals, 110 of 139 (79%) had searched for MBC-related information, specifically: patient information, anti-hormonal therapy, genetic testing, research, and psychosocial issues. CONCLUSIONS: Unmet information needs in MBC patients and health professionals were identified. Specific information on MBC should be developed to improve timely diagnosis, quality of life, treatment, and survival. A targeted website is an ideal tool to meet these needs. Therefore, we integrated these results into a user-centered design to develop an informative website, www.mannenmetborstkanker.nl.

Validity of thermography for measuring burn wound healing potential.

Accurate assessment of burn wound depth and the associated healing potential is vital in determining the need for surgical treatment in burns. Infrared thermography measures the temperature of the burn wound noninvasively, thereby providing indirect information on its blood flow. Previous research demonstrated that a small, low-priced, handheld thermal imager has an excellent reliability, but a moderate validity for measuring burn wound healing potential. A new and more sensitive version of this convenient device has become available. The aim of this study was to evaluate the validity of thermography for measuring burn wound healing potential, compared to Laser Doppler Imaging (LDI) as a reference standard. Thermal images and LDI scans were obtained from burn wounds between 2 and 5 days postburn. Temperature differences between burned and nonburned skin (ΔT) were calculated. To evaluate validity, ΔT values were compared to the healing potential categories assessed by LDI. Two receiver operating characteristic curves were created and two ΔT cutoff values were calculated to illustrate the ability to discriminate between burn wounds that heal in a time period of less than 14 days, between 14 and 21 days, and more than 21 days. Between June and October 2018, 43 burn wounds in 32 patients were measured. ΔT cutoff values of 0.6°C (sensitivity 68%, specificity 95%) and -2.3°C (sensitivity 30%, specificity 95%) were calculated to discriminate between burn wounds that heal in <14 and ≥14 days, and burn wound that heal in ≤21 and >21 days, respectively. This study shows a good validity of the feasible thermal imager for the assessment of burn wound healing potential. Therefore, we consider it a promising technique to be used for triage in local hospitals and general practices, and as a valuable addition to clinical evaluation in burn centers.

Using fibrin sealant for skin graft fixation to avoid sedation in children with burns: a prospective study.

OBJECTIVE: To investigate whether a fibrin sealant, Fitrix (Sanquin Blood Supply Foundation, The Netherlands), for fixation of skin grafts in children with burn wounds is less invasive and equally effective in comparison with skin staples. METHOD: A single-centre prospective observational cohort study was conducted. Children requiring skin grafting after burns were included and received the fibrin sealant. This group was compared with a retrospective control group of children whose skin grafts were fixed with skin staples. Study outcomes were graft take, graft dislocation, other wound complications, healing and need for sedation. RESULTS: In the fibrin sealant and the control groups, 17 and 27 patients were included, respectively. The percentage of total body surface area (%TBSA) grafted was smaller (p=0.028) in the fibrin sealant group (median 1.0, interquartile range (IQR) 1.5 versus 2.0, IQR 2.5). There was no significant difference in graft take or wound healing. There were two graft dislocations in the fibrin sealant group and none in the control group. Other complications included a patient with graft failure in the fibrin sealant group, and another patient with a vanishing graft and wound infection in the control group. There were fewer sedations in the fibrin sealant group compared with the control group (one versus 20, p<0.0001). CONCLUSION: The fibrin sealant used in this study was non-inferior for the fixation of skin grafts in comparison with skin staples, and avoided sedation procedures.

Patient-reported scar quality of adults after burn injuries: A five-year multicenter follow-up study.

Scar formation is an important adverse consequence of burns. How patients appraise their scar quality is often studied shortly after sustaining the injury, but information in the long-term is scarce. Our aim was, therefore, to evaluate long-term patient-reported quality of burn scars. Adults with a burn center admission of ≥1 day between August 2011 and September 2012 were invited to complete a questionnaire on long-term consequences of burns. We enriched this sample with patients with severe burns (>20% total body surface area [TBSA] burned or TBSA full thickness >5%) treated between January 2010 and March 2013. Self-reported scar quality was assessed with the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS). Patients completed this scale for their-in their opinion-most severe scar ≥5 years after burns. This study included 251 patients with a mean %TBSA burned of 10%. The vast majority (91.4%) reported at least minor differences with normal skin (POSAS item score ≥2) on one or more scar characteristics and 78.9% of the patients' overall opinion was that their scar deviated from normal skin. Patients with severe burns had higher POSAS scores, representing worse scar quality, than patients with mild/intermediate burns, except for color, which was high in both groups. A longer hospital stay predicted reduced scar quality (both mean POSAS and mean overall opinion of the scar) in multivariate analyses. In addition, female gender was also associated with a poorer overall opinion of the scar. In conclusion, this study provides new insights in long-term scar quality. Scars differed from normal skin in a large part of the burn population more than 5 years after burns, especially in those with severe burns. Female gender is associated with a poorer patients' overall opinion of their scar, which may be an indication of gender differences in perception of scar quality after burns.

Detection of bacteria in burn wounds with a novel handheld autofluorescence wound imaging device: a pilot study.

OBJECTIVE: To compare the detection of bacteria in burn wounds between an bacterial fluorescence imaging device MolecuLight i:X, (Canada), and standard microbiological swabs. METHODS: Wounds were swabbed three times on one occasion; once with a standard swab, once with a high-fluorescent area swab, indicating a bacterial load >104 colony-forming units (CFU)/gram and a finally with a non-fluorescent (nF) area swab. Proportion agreement of the microbiological results was calculated and the accuracy of the device to detect relevant bacteria was assessed. RESULTS: A total of 14 patients with 20 wounds participated in the study. Median post-burn day at sampling time was 21 days. Of the 20 wounds, nine had a positive swab result in either of the three swabs, and 11 showed a highfluorescent area. Overall, positive and negative proportion agreement between standard swab and high-fluorescent swab sample results were 100%. Sensitivity, specificity, positive and negative predictive values of presence of high-fluorescence were 78%, 64%, 64%, and 78%, respectively. For Pseudomonas aeruginosa detection, these results were 100%, 70%, 44% and 100%, respectively. CONCLUSION: The diagnostic accuracy of the bacterial fluorescence imaging device to detect relevant bacteria in burn wounds was moderate and the reliability was equal to standard swabbing. Further research in larger sample sizes and on the relevance of minimal bacterial load and its potential to help with Pseudomonas aeruginosa management is needed.

Course and Predictors of Pruritus Following Burns: A Multilevel Analysis.

Itch is a common problem after burns. Although the topic receives increasing attention, the number of prospective studies is limited. The aim of this study was to assess the influence of acute traumatic stress symptoms, controlled for injury characteristics, age and sex, on itch over a period of 18 months using multilevel analysis. A total of 226 respondents provided itch scores. Participants completed the Burn Itch Questionnaire during admission (n = 208) and at 3 (n =179), 12 (n =143) and 18 (n =99) months post-burn. They completed the Impact of Event Scale to assess acute traumatic stress symptoms during admission. Skin graft requirement, a higher level of acute traumatic stress symptoms and younger age were statistically significant predictors of a higher itch score. Younger age was particularly associated with higher itch scores during admission, whereas the effect of skin grafting was particularly observed at 3 months post-burn. This study replicates the predictive role of traumatic stress symptoms, which warrants further research.

Physical activity and survival of postmenopausal, hormone receptor-positive breast cancer patients: results of the Tamoxifen Exemestane Adjuvant Multicenter Lifestyle study.

BACKGROUND: Physical activity has been related to improved breast cancer outcomes. Especially in the older breast cancer population, physical activity may be important because old age is associated with comorbidities and decreased physical function. The purpose of this study was to investigate the relation between physical activity and overall survival, breast cancer-specific survival, and recurrence in several age groups of postmenopausal breast cancer patients. METHODS: The Tamoxifen Exemestane Adjuvant Multinational Lifestyle study was a side study of the Tamoxifen Exemestane Adjuvant Multinational trial and prospectively investigated lifestyle habits of postmenopausal, hormone receptor-positive breast cancer patients. The relations between prediagnosis and postdiagnosis physical activity and overall survival, breast cancer-specific survival, and recurrence-free survival were assessed with Cox regression and competing risk regression models. RESULTS: Among 521 patients, high levels of physical activity before and after the diagnosis were associated with better overall survival (the multivariate hazard ratios were 0.50 [95% confidence interval = 0.26-0.98] and 0.57 (95% confidence interval = 0.26-1.40] for patients who were very active before and after the diagnosis, respectively, in comparison with inactive patients). This was most evident in patients who were 65 years old or older. Physical activity was not significantly associated with breast cancer-specific survival or the relapse-free period. CONCLUSIONS: Overall survival was better for patients who were active before and after the diagnosis. In contrast with previous studies, breast cancer survival and the risk of recurrence were not significantly associated with physical activity. These findings confirmed the need for more studies investigating the use of physical activity to supplement breast cancer treatment in older patients.

The Nightingale study: rationale, study design and baseline characteristics of a prospective cohort study on shift work and breast cancer risk among nurses.

BACKGROUND: Evidence for the carcinogenicity of shift work in humans is limited because of significant heterogeneity of the results, thus more in-depth research in needed. The Nightingale Study is a nationwide prospective cohort study on occupational exposures and risks of chronic diseases among female nurses and focuses on the potential association between shift work and risk of breast cancer. The study design, methods, and baseline characteristics of the cohort are described. METHODS/DESIGN: The source population for the cohort comprised 18 to 65 year old women who were registered as having completed training to be a nurse in the nationwide register for healthcare professionals in the Netherlands. Eligible women were invited to complete a web-based questionnaire including full job history, a detailed section on all domains of shift work (shift system, cumulative exposure, and shift intensity) and potential confounding factors, and an informed consent form for linkage with national (disease) registries. Women were also asked to donate toenail clippings as a source of DNA for genetic analyses. Between October 6, 2011 and February 1, 2012, 31% of the 192,931 women who were invited to participate completed the questionnaire, yielding a sample size of 59,947 cohort members. The mean age of the participants was 46.9 year (standard deviation 11.0 years). Toenail clippings were provided by 23,439 participants (39%). DISCUSSION: Results from the Nightingale Study will contribute to the scientific evidence of potential shift work-related health risks among nurses and will help develop preventive measures and policy aimed at reducing these risks.

Thermal Imaging for Burn Wound Depth Assessment: A Mixed-Methods Implementation Study.

Background: Implementing innovations emerging from clinical research can be challenging. Thermal imagers provide an accessible diagnostic tool to increase the accuracy of burn wound depth assessment. This mixed-methods implementation study aimed to assess the barriers and facilitators, design implementation strategies, and guide the implementation process of thermal imaging in the outpatient clinic of a burn centre. Methods: This study was conducted between September 2022 and February 2023 in Beverwijk, The Netherlands. Semi-structured interviews with burn physicians guided by the Consolidated Framework for Implementation Research (CFIR) were conducted to identify barriers and facilitators. Based on the barriers, implementation strategies were developed with the CFIR-ERIC Matching Tool, and disseminated to support the uptake of the thermal imager. Subsequently, thermal imaging was implemented in daily practice, and an iterative RE-AIM approach was used to evaluate the implementation process. Results: Common facilitators for the implementation of the thermal imager were the low complexity, the relative advantage above other diagnostic tools, and benefits for patients. Common barriers were physicians' attitude towards and perceived value of the intervention, the low compatibility with the current workflow, and a lack of knowledge about existing evidence. Six implementation strategies were developed: creating a formal implementation blueprint, promoting adaptability, developing educational materials, facilitation, conducting ongoing training, and identifying early adopters. These strategies resulted in the effective implementation of the thermal imager, reflected by a >70% reach among eligible patients, and >80% effectiveness and adoption. Throughout the implementation process, compatibility, and available resources remained barriers, resulting in low ratings on RE-AIM dimensions. Conclusions: This study developed implementation strategies based on the identified CFIR constructs that impacted the implementation of a thermal imager for burn wound assessment in our outpatient clinic. The experiences and findings of this study could be leveraged to guide the implementation of thermal imaging and other innovations in burn care.

The efficacy of therapeutic interventions on paediatric burn patients' height, weight, body composition, and muscle strength: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. METHODS: A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn. RESULTS: Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% ( ± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support. CONCLUSIONS: Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers.

IDENTIFICATION OF POTENTIALLY MODIFIABLE FACTORS TO IMPROVE RECOGNITION AND OUTCOME OF NECROTIZING SOFT-TISSUE INFECTIONS.

ABSTRACT: Background : Necrotizing soft-tissue infections (NSTIs) present a surgical emergency of increasing incidence, which is often misdiagnosed and associated with substantial mortality and morbidity. A retrospective multicenter (11 hospitals) cohort study was initiated to identify the early predictors of misdiagnosis, mortality, and morbidity (skin defect size and amputation). Methods : Patients of all ages who presented with symptoms and were admitted for acute treatment of NSTIs between January 2013 and December 2017 were included. Generalized estimating equation analysis was used to identify early predictors (available before or during the first debridement surgery), with a significance level of P < 0.05. Results : The median age of the cohort (N = 216) was 59.5 (interquartile range = 23.6) years, of which 138 patients (63.9%) were male. Necrotizing soft-tissue infections most frequently originated in the legs (31.0%) and anogenital area (30.5%). More than half of the patients (n = 114, 54.3%) were initially misdiagnosed. Thirty-day mortality was 22.9%. Amputation of an extremity was performed in 26 patients (12.5%). Misdiagnosis was more likely in patients with a higher Charlson Comorbidity Index (ß = 0.20, P = 0.001), and less likely when symptoms started in the anogenital area (ß = -1.20, P = 0.003). Besides the established risk factors for mortality (septic shock and age), misdiagnosis was identified as an independent predictor of 30-day mortality (ß = 1.03, P = 0.01). The strongest predictors of the final skin defect size were septic shock (ß = 2.88, P < 0.001) and a skin-sparing approach to debridement (ß = -1.79, P = 0.002). Conclusion : Recognition of the disease is essential for the survival of patients affected by NSTI, as is adequate treatment of septic shock. The application of a skin-sparing approach to surgical debridement may decrease morbidity.

Associations of night shift work with weight gain among female nurses in The Netherlands: results of a prospective cohort study.

OBJECTIVE: This study aimed to prospectively investigate associations of working night shifts with weight gain in the Nightingale Study, a large cohort of female nurses. METHODS: This study included 36 273 registered nurses, who completed questionnaires in 2011 and 2017. Cumulative number of nights, mean number of nights/month and consecutive number of nights/month in 2007-2011 were assessed. We used Poisson regression to estimate multivariable-adjusted incidence rate ratios (IRR) of >5% weight gain from 2011 to 2017 among all participants and assess risk of development of overweight/obesity (BMI≥25 kg/m2) among women with healthy baseline body mass index. The reference group consisted of women who never worked nights. RESULTS: Overall, working night shifts in 2007-2011 was associated with >5% weight gain [IRR 1.07, 95% confidence interval (CI) 1.01-1.13]. Associations differed by menopausal status in 2011, with an increased risk of gaining >5% weight limited to postmenopausal women who worked nights (IRR 1.23, 95% CI 1.10-1.38). Postmenopausal women had an increased risk of >5% weight gain when they worked on average ≥4 nights/month (4-5: IRR 1.29, 95% CI 1.09-1.52, ≥6: IRR 1.27, 95% CI 1.11-1.47) or ≥4 consecutive nights/month (IRR 1.37, 95% CI 1.19-1.58), compared to postmenopausal women who never worked nights. For postmenopausal women with healthy weight at baseline, night shift work was associated with an increased risk of overweight/obesity at follow-up (IRR 1.24, 95% CI 1.03-1.50). CONCLUSIONS: Working night shifts was associated with a slightly increased risk of weight gain and overweight/obesity development among women who were postmenopausal at study inclusion. Our findings emphasize the importance of health promotion to maintain a healthy weight among (postmenopausal) night workers.

Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial.

BACKGROUND: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. METHODS: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. RESULTS: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. CONCLUSIONS: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.