Variations In Treatment Protocols Research Articles

Efficacy of arm crank ergometry on individuals with spinal cord injury: A systematic review of randomized controlled trials.

To investigate the efficacy of arm crank ergometry (ACE) on physical, psychological, and quality of life outcomes in individuals with spinal cord injury (SCI). A comprehensive search was conducted on PubMed, Scopus, MEDLINE, Physiotherapy Evidence Database (PEDro), Web of Science, REHABDATA, and Embase from inception until July 2023. Studies were included if the sample was composed of individuals with SCI, the intervention followed an ACE intervention, and the study was a randomized controlled trial including at least one outcome measure evaluating physical, psychological, or quality of life. The PEDro scale was used to assess the methodological quality of the included studies. The meta-analysis was not feasible due to the heterogeneity in the treatment protocols and outcome measures among the selected studies. Of 1013 articles, seven studies (n = 200), with 16% of participants being female, were included in this review. The scores on the PEDro scale ranged from 6 to 8, with a median score of 7. There were variations in treatment protocols and outcome measures, resulting in heterogeneous findings. The effects of the ACE interventions on physical, psychological, and quality of life outcomes showed inconsistency. ACE training proves to be a suitable and safe intervention for individuals with traumatic SCI. Nevertheless, the existing evidence concerning its effects on physical, psychological, and quality of life outcomes in individuals with SCI is limited. Further trials are required to investigate the effects of various ACE training protocols on SCI populations.

Hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of ovarian cancer

Key content Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery is a proposed additional treatment in the management of advanced tubo‐ovarian cancer. Additional organisational approvals, costs, changes to theatre infrastructure and pre‐, intra‐, and post‐operative management considerations are required to implement HIPEC in a clinical setting. Current meta‐analysis data suggest that in the setting of interval cytoreductive surgery, HIPEC prolongs overall survival and progression‐free survival. There is currently no evidence of benefit in the setting of primary surgery or recurrent disease, but results of ongoing clinical trials are pending. Learning objectives To understand the mechanism of action, safety and efficacy of HIPEC as an adjuvant treatment in tubo‐ovarian cancer. Ethical issues Because of variation in treatment protocols and heterogeneity of reported outcomes, HIPEC has not yet been adopted into standard practice. Further studies assessing its benefit, mainly in the setting of primary cytoreduction, are ongoing.

Disease severity and status in Stevens-Johnson syndrome and toxic epidermal necrolysis: Key knowledge gaps and research needs.

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are on a spectrum of cutaneous drug reactions characterized by pan-epidermal necrosis with SJS affecting < 10% of body surface area (BSA), TEN > 30%, and SJS/TEN overlap between 10 and 30%. Severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is a validated tool to predict mortality rates based on age, heart rate, BSA, malignancy and serum urea, bicarbonate, and glucose. Despite improved understanding, SJS/TEN mortality remains constant and therapeutic interventions are not universally accepted for a number of reasons, including rarity of SJS/TEN; inconsistent definition of cases, disease severity, and endpoints in studies; low efficacy of interventions; and variations in treatment protocols. Apart from mortality, none of the other endpoints used to evaluate interventions, including duration of hospitalization, is sufficiently standardized to be reproducible across cases and treatment centers. Some of the gaps in SJS/TEN research can be narrowed through international collaboration to harmonize research endpoints. A case is made for an urgent international collaborative effort to develop consensus on definitions of endpoints such as disease status, progression, cessation, and complete re-epithelialization in interventional studies. The deficiencies of using BSA as the sole determinant of SJS/TEN severity, excluding internal organ involvement and extension of skin necrosis beyond the epidermis, are discussed and the role these factors play on time to healing and mortality beyond the acute stage is highlighted. The potential role of artificial intelligence, biomarkers, and PET/CT scan with radiolabeled glucose as markers of disease status, activity, and therapeutic response is also discussed.

In dogs with aural haematoma does draining and injecting corticosteroids versus drainage alone reduce the risk of recurrence?

PICO question&#x0D; In dogs with aural haematomas does draining and injecting corticosteroids versus drainage alone reduce the risk of recurrence?&#x0D;  &#x0D; Clinical bottom line&#x0D; Category of research question&#x0D; Treatment&#x0D; The number and type of study designs reviewed&#x0D; Three papers were critically reviewed, a retrospective multi-centre cohort study, a randomised case control trial and an observational survey&#x0D; Strength of evidence&#x0D; Weak&#x0D; Outcomes reported&#x0D; Drainage alone at daily or weekly frequency consistently resulted in aural haematoma (AH) recurrence and lack of resolution. Corticosteroid instillation alongside drainage reduced the risk of rapid recurrence for AHs, across both the cohort and the case control studies, provided drainage was frequent&#x0D; Conclusion&#x0D; The strength of evidence for local steroid instillation was weak given the type of studies reviewed, alongside small sample sizes and variations in treatment protocol. However, consistently drainage alone appears an insufficient means of addressing AHs in dogs.&#x0D; In cases where frequent drainage was the chosen treatment option, the addition of local corticosteroid application appeared to improve the outcome compared to drainage alone.&#x0D; However, as systemic treatment was often employed alongside local corticosteroid instillation, success cannot necessarily be attributed solely to local treatment. Larger, randomised control trials would be required to assess the effect of each individual intervention providing clearer evidence for the most effective medical protocol for treating aural haematomas in dogs&#x0D;  &#x0D; How to apply this evidence in practice&#x0D; The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.&#x0D; Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.&#x0D;  &#x0D;

Facial Basal Cell Carcinoma: A Study of Causative Factors and Site-based Algorithm for Surgical Reconstruction.

Basal cell carcinoma (BCC) can be categorized as one of the commonly occurring skin malignancies in the world, with several variations in treatment protocols. Sun exposure has been attributed to its causality; however, other factors such as gender, age, and occupation also affect its incidence. We aimed to characterize the patient population who underwent surgical management for facial BCC at a tertiary referral hospital. Further, we have described an algorithm that may aid in surgical decision-making based on the location of the lesions on the face. We performed a retrospective chart review of all patients who presented with a facial BCC to our institution between 2018 and 2019. Data regarding patients' demographic characteristics, skin phototype, average sun exposure, occupation, residence place (rural or urban), and surgical outcomes were recorded. Sixty-eight patients underwent reconstructive procedures after oncologic resection of facial BCC: 41.2% were males and 58.8% were females. Forty-eight (70.6%) patients were from rural areas, and 20 patients (29.4%) from urban areas (P < 0.001). Twenty-six patients reported >2 h of sunlight exposure, 16 reported <2 h of continuous sun exposure, and 26 reported intermittent sun exposure. A significantly higher proportion of patients with facial BCC presented with a Fitzpatrick skin type 4 in comparison to types 3 and 5 (P < 0.001). The most common reconstructive technique was the V-Y advancement flap (n=22, 32.4%), followed by the forehead flap (n=12, 17.6%) and the Limberg flap (n=12, 17.6%). All the flaps were healthy post-operatively and none of them suffered from flap failure, infection, or suture line dehiscence. There was no recurrence at 1-year follow-up. This study gives a correlation between incidence of BCC and age, gender, and sun exposure in Indian population. In our experience, local flaps yield outstanding results and are the first choice for reconstruction of the face when composite defects are not present. Our algorithm aids in surgical decision-making.

P–394 Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: a systematic review and meta-analysis

Abstract Study question What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes. Summary answer The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention. Study design, size, duration We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI). Main results and the role of chance We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Limitations, reasons for caution Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit. Trial registration number CRD42019148517

A national survey of orthodontists in Malaysia and their use of functional appliances for Class II malocclusions

Abstract Objectives The aim of this study was to evaluate the use of functional appliances by the currently practising orthodontists in Malaysia. The objectives were to identify the different types of functional appliances used by Malaysian orthodontists and to investigate the variation in treatment protocols when attempting growth modification. Methods An online questionnaire consisting of 24 open-ended and multiple-choice questions was emailed to members of the Malaysian Association of Orthodontists (MAO) (n = 183). The survey was based on a previous study conducted by members of the British Orthodontic Society and was modified to suit the Malaysian population. The data were analysed using SPSS to generate frequency tables and descriptive statistics. Results Seventy-two responses were received from current Malaysian orthodontists. Of the respondents, 71% practised in a government setting and 29% were in private practice. The Clark Twin Block was the most frequently used functional appliance by 90% of Malaysian orthodontists. Many of the respondents (57%) prescribed full-time wear of removable functional appliances for 6–9 months (except during mealtimes) (51%). Following active removable functional appliance therapy, 91% prescribed a period of retention which involved a reduction in the duration of wear. The retention phase extended for 2 to 3 months (41%) or for 4 to 6 months (39%) for the majority of the respondents. Conclusions The Clark Twin Block is the most frequently-used functional appliance for the management of a Class II malocclusion by orthodontists currently practising in Malaysia.

Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: A systematic review and meta‐analysis

Recurrent implantation failure (RIF) affects 10% of couples undergoing assisted conception, often due to poor endometrial receptivity. We conducted a systematic review and meta-analysis to evaluate the effectiveness of Intra-venous intralipid (IVI) in improving pregnancy rates in women with history of RIF using. We searched MEDLINE, EMBASE, and CENTRAL for any randomized trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analyzed data using a random effect model. We included five randomized trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, risk ratio [RR] 1.55, 95% confidence interval [CI] 1.16-2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95% CI 1.42-2.35, I2 0%) post treatment compared to no intervention. Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. There is limited evidence to support the use of IVI at the time of embryo transfer in women with the history of RIF. More research is needed before adopting it in clinical practice.

Utilization of Teledentistry in Antimicrobial Prescribing and Diagnosis of Infectious Diseases during COVID-19 Lockdown.

Objectives  This study aimed to analyze Jordanian dentists’ inquiries on oral infections and antimicrobial prescribing using dental professional WhatsApp groups during coronavirus disease lockdown period. Materials and Methods  Three professional WhatsApp groups of Jordanian dentists were reviewed and analyzed for inquiries posted during the period from January to May 2020. Inquiries were sent from patients to their dentists who posted these inquiries to the professional WhatsApp dental groups for consultation and professional advice. All queries regarding oral infections and antimicrobial prescribing were extracted and analyzed. Results  Three WhatsApp professional groups with a total numbers of members of 750 dentists who posted queries about their patients were included in this study. Dentist members posted queries about their patients to these professional WhatsApp groups. There was a total of 32 inquiries regarding oral lesions and 11 consultations regarding prescribing and dental management of medically compromised patients giving a total of 43 consultations. Among which there were 19 inquiries on oral infections and 9 inquiries on antimicrobial prescribing giving a total of 28 consultations. Most common inquiries were on bacterial infections (localized dentoalveolar abscess, pericoronitis, cellulitis, and lymphoid hyperplasia of the tongue), viral herpetic infections, and Candida infections (erythematous and pseudomembranous candidiasis). Conclusions Many dental practitioners cannot distinguish the correct diagnostic features of oral infections particularly viral and fungal infections. Continuing education should be considered to focus on clinical manifestations of various oral infections. Further, educational activities that focus on variations in treatment protocols for various infections should be introduced particularly those that concern indications for antimicrobial prescribing.

Outcomes in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia (ALL): A Report from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC)

Introduction Acute lymphoblastic leukemia (ALL) diagnosed in adolescent and young adults (AYA) poses unique challenges. Despite using more intensive "pediatric-type" protocols, outcomes are generally inferior to those seen in children. The reasons are wide ranging, but when compared to pediatric ALL, AYA ALL has higher-risk biology, poorer tolerance to intensive treatments, and worse compliance with treatment regimens. India has one of the largest AYA populations in the world and AYA-ALL form a significant proportion of leukemias. The Indian acute leukemia research database [INwARD] was established in 2018 and had reported outcomes of ALLs from various centers of all age groups (Korula A, et al. Blood 2018 132:1374). Here, we present data focused on AYA-ALL from this database. Methods Retrospective data of AYA (15-29 years) patients with ALL (diagnosed between January 2012 to December 2017) from 9 centers were entered into an independent centralized online data capture system and analyzed for presenting characteristics, treatment and survival outcomes. Protocol choice was based on individual-center preference. For the purpose of this analysis, patients with WBC ≥30000 (B cell) and ≥100,000 (T-cell and other subtypes) were considered as high risk. Intensive protocols (MCP-841, BFM-95, COG), predominantly meant for children were labeled as "pediatric-type" and less intense protocols (GMALL, Hyper CVAD, UKALL) were considered as "adult-type". Results In the 6-year period, 1454 patients were registered [Males: 1114(76%), Median age: 20 years (15-29), Fig. 1.B; Subtype: B -ALL: 916(63%), T-ALL: 396 (27%); Fig. 1.C; High risk disease: 406 (28%)]. Of these,1100 (75%) underwent treatment. Poor financial support was the major reason for not taking treatment (Fig. 1.A). "Pediatric-type" protocols were used in 881 (81%) patients. After induction, 72% achieved complete remission (CR), 11% were refractory, 4% died during induction and 14% were not evaluable. Minimal residual disease was assessed in 581 and was present in 356 (61%). Attainment of CR, induction mortality, or MRD achievement was not affected by the type of regimen. Among these 1100 patients, 138 (12%) were lost to follow up and did not complete treatment. BCR ABL was tested in 636 and was positive in 112 (17%) [19% among patients with B-ALL (107/557)]and 106 of these were treated with additional tyrosine kinase inhibitors [imatinib (N=83) and dasatinib (N=23)]. Survival analysis: After a median follow up of 21 months, 270 patients relapsed [median time to relapse: 24 months (73% medullary, 17% CNS or testis, and 10% had a combined relapse) and 259 had died. The estimated 2-year event-free (EFS), relapse-free (RFS) and overall survival (OS) were 64%, 75% and 75% respectively. On univariate analysis the factors associated with inferior survival were as follows: EFS: WBC count ≥30,000/cmm, and ECOG PS 2-4; RFS: WBC count ≥30,000/cmm and ECOG PS 2-4; OS: use of "adult-type" protocols, ECOG PS 2-4, and BCR-ABL positive disease. On multivariate cox regression analysis, the only factors associated with inferior OS were: use of "adult" protocols (HR: 1.6), and BCR -ABL positive status (HR1.56) (Fig. 1.D). High WBC count at presentation predicted for inferior RFS while no factor could predict EFS on multivariate analysis. Conclusions In a multicenter analysis of AYA-ALL from different parts of India, we found that a quarter of newly diagnosed patients do not start treatment and another 12% are lost from follow up before treatment completion. Majority (80%) of the centers used "pediatric-type" protocols to treat AYA-ALL. Though superior survival was achieved with "pediatric-type" protocols, results must be interpreted with caution as these regimens were likely to be used more often in in younger patients. Variations in treatment protocols used between centers and the retrospective nature of the data are other caveats. Despite these limitations, this is one of the largest reports of AYA ALL from any part of the world and serves as a benchmark for planning prospective studies. Disclosures No relevant conflicts of interest to declare.

IMMU-45. CAR-T TREATMENT OF NOVEL MOUSE MODEL OF EGFRVIII+ GBM MIRRORS CLINICAL TRIAL OUTCOMES AND PROVIDES A SYNGENEIC PLATFORM FOR THE INVESTIGATION OF CAR-T MECHANISMS OF ACTION

Abstract Despite the recent successes in cancer immunotherapy, brain tumors continue to present a significant challenge due to the unique relationship between the CNS and the immune system. Adoptive cell transfer of chimeric antigen receptor T-cells (CAR-T cells) targets tumor-associated and tumor-specific antigens. Multiple clinical trials testing CAR-T cells in the brain tumor setting have demonstrated the feasibility and safety, but also highlighted the limitations and continued need for treatment improvement. These challenges include recurrence of tumor cells that do not express the target antigens and induction of immuno-regulatory mechanisms, such as PD-L1 expression within the tumor. In this study, we used a murine GBM cell line (SB28), engineered to express the tumor-specific neoantigen human epidermal growth factor receptor variant III, to study the in vivo effects of EGFRvIII-CAR T-cells in a novel fully immunocompetent mouse model. SB28 cells have been shown to recapitulate key characteristics of human GBM, such as aggressive growth, low mutation burden, and resistance to immune checkpoint blockade therapy, and therefore, allow us to investigate many clinically relevant questions and variations in treatment protocol. Intravenous administration of CAR-transduced murine T-cells in EGFRvIII-expressing SB28 tumors showed survival benefit only when preceded by a lymphodepleting regimen. Despite prolonging survival, EGFRvIII-CAR-T cells were not curative, and the recurrent tumors displayed profound antigen loss, similar to post-treatment human tumor samples. Preliminary mechanistic studies revealed upregulation of IFNγ-inducible molecules, such as PD-L1 on tumor cells and tumor-infiltrating myeloid cells, as well as the emergence of a small, but discreet population of activated antigen presenting cells. Currently ongoing studies are aimed at delineating the exact molecular and cellular changes in the tumor microenvironment in response to the EGFRvIII-CAR T-cell treatment, in combination with clinically relevant therapies targeting the largely immunosuppressive tumor myeloid compartment

Venous thromboembolism (VTE) prophylaxis in severely injured patients: an international comparative assessment

PurposeVenous thromboembolisms (VTE) are a major concern after acute survival from trauma. Variations in treatment protocols for trauma patients exist worldwide. This study analyzes the differences in the number of VTE events and the associated complications of thromboprophylaxis between two level I trauma populations utilizing varying treatment protocols.MethodsInternational multicenter trauma registry-based study was performed at the University Medical Center Utrecht (UMCU) in The Netherlands (early commencement chemical prophylaxis), and Harborview Medical Center (HMC) in the United States (restrictive early chemical prophylaxis). All severely injured patients (ISS ≥ 16), aged ≥ 18 years, and admitted in 2013 were included. Primary outcomes were VTE [deep venous thrombosis (DVT) (no screening), pulmonary embolism (PE)], and hemorrhagic complications.ResultsIn UMCU, 279 patients were included and in HMC, 974 patients. Overall, 75% of the admitted trauma patients in UMCU and 81% in HMC (p < 0.001) received thromboprophylaxis, of which 100% in and 75% at, respectively, UMCU and HMC consisted of chemical prophylaxis. From these patients, 72% at UMCU and 47% at HMC (p < 0.001) were treated within 48 h after arrival. At UMCU, 4 patients (1.4%) (PE = 3, DVT = 1) and HMC 37 patients (3.8%) (PE = 22, DVT = 16; p = 0.06) developed a VTE. At UMCU, a greater percent of patients with VTE had traumatic brain injuries (TBI). Most VTE occurred despite adequate prophylaxis being given (75% UMCU and 81% HMC). Hemorrhagic complications occurred in, respectively, 4 (1.4%) and 10 (1%) patients in UMCU and HMC (p = 0.570). After adjustment for age, ISS, HLOS, and injury type, no significant difference was demonstrated in UMCU compared to HMC for the development of VTE, OR 2.397, p = 0.102 and hemorrhagic complications, OR 0. 586, p = 0.383.ConclusionsA more early commencement protocol resulted in almost twice as much chemical prophylaxis being started within the first 48 h in comparison with a more delayed initiation of treatment. Interestingly, most episodes of VTE developed while receiving recommended prophylaxis. Early chemical thromboprophylaxis did not significantly increase the bleeding complications and it appears to be safe to start early.

Children with Hemiparesis Arm and Movement Project (CHAMP): protocol for a multisite comparative efficacy trial of paediatric constraint-induced movement therapy (CIMT) testing effects of dosage and type of constraint for children with hemiparetic cerebral palsy

IntroductionThe Children with Hemiparesis Arm and Movement Project (CHAMP) addresses two pressing issues concerning paediatric constraint-induced movement therapy (CIMT): effects of two dosages and two types of constraint on functional...

Wednesday, September 26, 2018 2:00 PM – 3:00 PM Improving Quality of Life for Patients with Tumors: 78. Optimal treatment strategy for newly diagnosed chordoma of the spine: results of an international survey to design a prospective cohort study

BACKGROUND CONTEXT Treatment strategies for spinal chordomas are heterogeneous and are mainly driven by institutional biases and local protocols. Surgery plays a central role in their management but the extent of surgery and the role of adjuvant therapy, particularly radiation therapy, is not standard across centers. PURPOSE The aims of this international collaborative effort are to identify the main management options for newly diagnosed chordoma of the spine, understand the variations in treatment protocols among experienced centers, and to consequently design a multicenter prospective cohort study to help determine the best multimodal treatment for this patient population. STUDY DESIGN/SETTING A survey was distributed to 39 spinal oncology specialists in neurosurgery, orthopedic surgery, and radiation oncology from 29 centers. METHODS Two clinical scenarios were presented and the preferred management strategy was queried among the respondents: (1) a newly diagnosed chordoma of the spine when en bloc resection is feasible with acceptable morbidity, and (2) when en bloc resection is not feasible as it would result in significant morbidity. Based on the results of this survey, a prospective cohort study combining centers with similar treatment strategies for newly diagnosed chordoma of the spine is proposed. RESULTS When en bloc resection is feasible with acceptable morbidity, most participants (79.5%) favored an en bloc resection without preoperative neo-adjuvant radiation treatment (RT). The main disagreement is with the role of postoperative radiation with 41% giving RT only if positive margins and 38% giving adjuvant RT to everyone irrespective of marginal status. When en bloc resection would result in significant morbidity, results were more evenly distributed and 33% of respondents preferred to do a deliberate intralesional resection followed by RT, and 33% chose to give neo-adjuvant RT prior to surgery. By combining centers with similar philosophies, three distinct treatment cohorts were identified for tumors for which en bloc resection is feasible with acceptable morbidity and 5 treatment groups for tumors in which en bloc resection would result in significant morbidity. These will constitute the distinct treatment cohorts of a prospective international cohort study. CONCLUSIONS The results of this survey allowed the design of an international collaborative prospective cohort study to uncover the best treatment strategy for patient with spinal chordomas. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Shunt-dependent hydrocephalus: management style among members of the American Society of Pediatric Neurosurgeons.

OBJECTIVE The authors conducted a survey to evaluate differences in the understanding and management of shunt-dependent hydrocephalus among members of the American Society of Pediatric Neurosurgeons (ASPN). METHODS Surveys were sent to all 204 active ASPN members in September 2014. One hundred thirty responses were received, representing a 64% response rate. Respondents were asked 13 multiple-choice and free-response questions regarding 4 fundamental problems encountered in shunted-hydrocephalus management: shunt malfunction, chronic cerebrospinal fluid (CSF) overdrainage, chronic headaches, and slit ventricle syndrome (SVS). RESULTS Respondents agreed that shunt malfunction occurs most often as the result of ventricular catheter obstruction. Despite contrary evidence in the literature, most respondents (66%) also believed that choroid plexus is the tissue most often found in obstructed proximal catheters. However, free-text responses revealed that the respondents' understanding of the underlying pathophysiology of shunt obstruction was highly variable and included growth, migration, or adherence of choroid plexus, CSF debris, catheter position, inflammatory processes, and CSF overdrainage. Most respondents considered chronic CSF overdrainage to be a rare complication of shunting in their practice and reported wide variation in treatment protocols. Moreover, despite a lack of evidence in the literature, most respondents attributed chronic headaches in shunt patients to medical reasons (for example, migraines, tension). Accordingly, most respondents managed headaches with reassurance and/or referral to pain clinics. Lastly, there were variable opinions on the etiology of slit ventricle syndrome (SVS), which included early shunting, chronic overdrainage, and/or loss of brain compliance. Beyond shunt revision, respondents reported divergent SVS treatment preferences. CONCLUSIONS The survey shows that there is wide variability in the understanding and management of shunt-dependent hydrocephalus and its complications. Such discrepancies appear to be derived partly from inconsistent familiarity with existing literature but especially from a paucity of high-quality publications.

The Americleft Psychosocial Outcomes Project: A Multicenter Approach to Advancing Psychosocial Outcomes for Youth With Cleft Lip and Palate.

Cleft lip and/or palate (CL/P) are among the most common of all birth defects. Habilitation requires multiple surgeries and other therapies throughout childhood and adolescence. While multidisciplinary care is recommended, there is a great deal of variation in treatment protocols for this condition. There is ample evidence that children with CL/P are at risk for psychosocial problems. However, to date, few studies have systematically investigated parent and patient self-reported psychosocial and quality of life (QOL) outcomes for children with CL/P as they relate to variations in treatment protocols. The Americleft Outcomes project was initiated to demonstrate and document outcomes to be expected with team care, and to define the key features or characteristics of various team treatment protocols and procedures that are associated with more or less favorable/desirable outcomes. This article will describe the psychosocial component of the Americleft Outcomes project that is aimed at developing a protocol that will allow cross team assessment of psychosocial outcomes for children with CL/P in relationship to the treatments they received. The protocol will be detailed along with a description of the process and considerations that were instrumental in the development of the project. Stakeholder input about the project's perceived relevance to families of children with CL/P will be reported. The paper concludes with a discussion of the challenges encountered with this project, clinical implications, and future directions.

Laser treatment of infantile hemangioma: A systematic review.

To systematically review studies of laser treatment of infantile hemangioma (IH). We searched multiple databases including MEDLINE® and EMBASE from 1982 to June 2015. Two investigators independently screened studies against predetermined criteria and extracted key data. Investigators independently assessed study risk of bias and the strength of the evidence of the body of literature. We identified 29 studies addressing lasers: 4 randomized controlled trials, 8 retrospective cohort studies, and 17 case series. Lasers varied across studies in type, pulse width, or cooling materials. Most comparative studies (n = 9) assessed variations of pulsed dye laser (PDL) and examined heterogeneous endpoints. Most studies reported on treatment of cutaneous lesions. Overall, longer pulse PDL with epidermal cooling was the most commonly used laser for cutaneous lesions; Nd:YAG was the most commonly used intralesionally. Most studies reported a higher success rate with longer pulse PDL compared with observation in managing the size of IH, although the magnitude of effect differed substantially. CO2 laser was used for subglottic IH in a single study, and was noted to have a higher success rate and lower complication rate than both Nd:YAG and observation. Studies comparing laser with β-blockers or in combination with β-blockers reported greater improvements in lesion size in combination arms versus β-blockers alone and greater effects of lasers on mixed superficial and deep IH. Strength of the evidence for outcomes after laser treatments ranged from insufficient to low for effectiveness outcomes. Strength of the evidence was insufficient for the effects of laser compared with β-blockers or in combination with β-blockers as studies evaluated different agents and laser types. Studies assessing outcomes after CO2 and Nd:YAG lasers typically reported some resolution of lesion size, but heterogeneity among studies limits our abilities to draw conclusions. Studies of laser treatment of IH primarily addressed different laser modalities compared with observation or other laser modalities. PDL was the most commonly studied laser type, but multiple variations in treatment protocols did not allow for demonstration of superiority of a single method. Most studies reported a higher success rate with longer pulse PDL compared to observation in managing the size of IH, although the magnitude of effect differed substantially. Studies generally found PDL more effective than other types of lasers for cutaneous lesions. When first introduced as a primary treatment for IH, various laser modalities generally offered superior outcomes compared with steroid therapy and observation. In the era of β-blocker therapy, laser treatment may retain an important role in the treatment of residual and refractory lesions.

Review of animal models used to study effects of bee products on wound healing: findings and applications

Abstract Non-healing wounds are associated with high morbidity and might greatly impact a patient’s well-being and economic status. For many years, scientific research has focused on developing and testing several natural and synthetic materials that enhance the rate of wound healing or eliminate healing complications. Honey has been used for thousands of years as a traditional remedy for many ailments. Recently, honey has reemerged as a promising wound care product especially for infected wounds and for wounds in diabetic patients. In addition to its proposed potent broad-spectrum antibacterial properties, honey has been claimed to promote wound healing by reducing wound hyperaemia, oedema, and exudate, and by stimulating angiogenesis, granulation tissue formation and epithelialisation. Several animal models, including large animals, dogs and cats, and different species of laboratory animals have been used to investigate the efficacy and safety of various natural and synthetic agents for wound healing enhancement. Interpreting the results obtained by these studies is, however, rather difficult and usually hampered by many limiting factors including great variation in types and origins of honey, the type of animal species used as models, the type of wounds, the number of animals, the number and type of controls, and variation in treatment protocols. In this article, we provide a comprehensive review of the most recent findings and applications of published experimental and clinical trials using honey as an agent for wound healing enhancement in different animal models.

Systematic review of clinical prediction tools and prognostic factors in aneurysmal subarachnoid hemorrhage.

Background:Clinical prediction tools assist in clinical outcome prediction. They quantify the relative contributions of certain variables and condense information that identifies important indicators or predictors to a targeted condition. This systematic review synthesizes and critically appraises the methodologic quality of studies that derive both clinical predictors and clinical predictor tools used to determine outcome prognosis in patients suffering from aneurysmal subarachnoid hemorrhage (SAH).Methods:This systematic review included prospective and retrospective cohort studies, and randomized controlled trials (RCTs) investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adult patients with aneurysmal SAH.Results:Twenty-two studies were included in this systemic review. Independent, confounding, and outcome variables were studied. Methodologic quality of individual studies was also analyzed. Included were 3 studies analyzing databases from RCTs, 8 prospective cohort studies, and 11 retrospective cohort studies. The most frequently retained significant clinical prognostic factors for long-term neurologic outcome prediction include age, neurological grade, blood clot thickness, and aneurysm size.Conclusions:Systematic reviews for clinical prognostic factors and clinical prediction tools in aneurysmal SAH face a number of methodological challenges. These include within and between study patient heterogeneity, regional variations in treatment protocols, patient referral biases, and differences in treatment, and prognosis viewpoints across different cultures.

Reply to "Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study" by Redmond et al.

Dear Editor: In a recent article in Neuro-Oncology, “Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study,”1 the connection between radiation dose and cognitive outcomes was evaluated. This is an interesting and important area of research that is inherently difficult to study because of the wide variation in treatment protocols. There are several methodological observations that may be important to consider when interpreting the findings of this study. First, the reported relationship between radiation dose and neurocognitive outcomes is difficult to interpret. For example, 74% of the patients were treated with 50–60 Gy radiation, with an overall mean dosage of 42.9 Gy. Only 3 patients (16% of the sample) were treated with 21–49 Gy radiation, and only 2 patients (11% of the sample) were treated with 0–20 Gy radiation. Because of these uneven and small individual sample sizes, it is very difficult to make comparisons among groups in neurocognitive functioning. In addition, there does not appear to be adequate variance within the patient sample (74% of patients were in the highest dose group) to draw conclusions regarding dose effects, particularly for those receiving <50–60 Gy radiation. Second, findings are very difficult to generalize because of the heterogeneity of the sample. Patients ranged in age from 1 to 18 years at the time of radiation, with a standard deviation of 1.1–18.6 years of age. To address this wide age range, the authors state in the Discussion that “Because we used standardized, age-adjusted scores for our analysis of the neurocognitive tests, we would not expect this difference to have an impact on our results.” The authors appear to have used raw scores instead of normative data and standardized scores and controlled for age in the regression analysis. Controlling for age at the time of radiation dose is not equivalent to using normative standardized scores. It is not stated in the manuscript why this method was chosen. Moreover, it appears that controlling for age at the time of radiation is counterintuitive because age at time of radiation moderates cognitive functioning and brain maturational trajectories.2 In other words, age at time of radiation and neurocognitive performance is not random but likely strongly correlated and contributory. The same argument might be made for controlling for presence or absence of chemotherapy; controlling for a variable that is likely to affect an outcome measure in one group but not the other (ie, patient group but not control group) may be artificially masking important and significant variance. On a similar note, neurocognitive testing was attempted at baseline (1–18 years of age) and at around 6, 15, and 27 months after completion of radiation treatment. The time between diagnosis and baseline testing ranged from 14 to 2284 days. It is theoretically and conceptually problematic that some patients received baseline testing years after diagnosis, whereas others were tested 2 weeks after diagnosis. There are many variables that may account for differences in neurocognitive functioning (eg, health status, time away from school, age differences, and chemotherapy effects) beyond radiation dose. This weakens the interpretation of the independent and dependent variables and overall results of the study. The study would be improved by clearly defined and more homogenous groups, to provide more ecologically valid information. The use of statistical covariates likely to affect outcome measures should also be clarified if indeed the results are to inform clinical practice and ongoing research. Conflict of interest. None declared.