Challenges in collecting information on sexual orientation and gender identity for cancer patients: perspectives of hospital and central cancer registry abstractors.

PURPOSE: Sexual and gender minority (SGM) populations experience cancer treatment and survival disparities; however, inconsistent sexual orientation and gender identity (SOGI) data collection within clinical settings and the cancer surveillance system precludes population-based research toward health equity for this population. This qualitative study examined how hospital and central registry abstractors receive and interact with SOGI information and the challenges that they face in doing so. METHODS: We conducted semi-structured interviews with 18 abstractors at five Surveillance, Epidemiology, and End Results (SEER) registries, as well as seven abstractors from commission on cancer (CoC)-accredited hospital programs in Iowa. Interviews were transcribed, cleaned, and coded using a combination of a priori and emergent codes. These codes were then used to conduct a descriptive analysis and to identify domains across the interviews. RESULTS: Interviews revealed that abstractors had difficulty locating SOGI information in the medical record: this information was largely never recorded, and when included, was inconsistently/not uniformly located in the medical record. On occasion, abstractors reported situational recording of SOGI information when relevant to the patient's cancer diagnosis. Abstractors further noticed that, where reported, the source of SOGI information (i.e., patient, physician) is largely unknown. CONCLUSION: Efforts are needed to ensure standardized implementation of the collection of SOGI variables within the clinical setting, such that this information can be collected by the central cancer registry system to support population-based equity research addressing LGBTQ + disparities.

Exploring variation in length of hospital stay among an elderly cohort of acute surgical admissions.

Aim Increased length of stay (LOS) indicates complex health care needs. It is unclear if age alone can be used as an indicator of longer hospital stays. Methods Retrospective review of acute surgical admissions (2016-2018) was performed, dividing data into three age groups (Group 1 (ages 65­74), Group 2 (ages 75­84) and Group 3 ( aged 85 and above). Effect of the independent variables; age, Groups of Episodes with similar diagnosis (GESD) and surgical interventions was noted on the LOS as well as discharge disposition and mortality. Subset analysis was performed for admissions with above average LOS. Results 1880 (27.7%) patients (total admissions=6793) were analysed. Mean LOS in each age group was 12.5, 13.3 and 12.5 days respectively (p=0.68). There was a mean 13 day increase with acute surgical intervention under General Anaesthesia, in comparison to 7.3 days and 5 days for Interventional Radiology and emergency endoscopy. 1496 (79.6%) patients were discharged home. 118 (66.0%) patients transferred to convalescent centres were over 75 years. Among those with above average LOS no significant correlation was found between sex, diagnosis, interventions with longer LOS. Discussion In acute settings, variables other than age are important to understand the variation in LOS. LOS is significantly influenced by diagnosis and acute intervention. Once patients exceed average LOS, resources should be explored to facilitate discharge planning.

Injection of freshly collected autologous adipose tissue in complicated pilonidal disease: a prospective pilot study.

BACKGROUND: Pilonidal sinus disease (PSD) is a frequent disorder. Treatment failure and recurrence are common, leading to significant morbidity. The aim of this study was to investigate the impact and need for repeated treatment of injected autologous adipose tissue into non-healing PSD wounds and primary anal-near PSD or anal-near recurrence. METHODS: At the Department of Surgery, Randers Regional Hospital, Denmark, a prospective pilot study was conducted on consecutive PSD patients with lack of healing 3 months after surgery (Bascom's cleft lift) or with primary or recurrent anal-near pilonidal sinus disease from December 2018 to March 2020. The primary endpoint was time to healing. Autologous adipose tissue was harvested from the patients and injected into the lesions after surgical revision. Patients were examined 2 and 12 weeks after surgery. Patients with lack of healing after 12 weeks (undermining or no skin coverage) were offered re-injection. RESULTS: We included 30 patients [26 men and 4 women, median age 24 years (range 18-59 years)]. Complete healing was achieved in 25 patients [83.3%; 95% CI (69.9-96.7)]. Two patients had recurrence (6.7%). The median time to complete healing was 159 (189) days. The mean operation time was 70.6 ± 23.7 min and the mean amount of injected autologous adipose tissue was 19 ± 10 ml. There were no major complications. CONCLUSION: Freshly collected autologous adipose tissue injected into chronic non-healing or primary and recurrent PSD lesions near the anal verge is safe and efficient.

Discharge destination after hip fracture: findings from the Irish hip fracture database.

PURPOSE: Although home continues to be the place from which the majority of patients are admitted, less than one third of patients are Discharged Directly Home (DDH) following hip fracture. Once ready for discharge, DDH as opposed to Discharge to an Alternative Location (DAL), i.e., community care, rehabilitation facility or long-term care, is a high priority for patients and clinicians alike. Not only is DDH integral to the quality of life of patients, it is also an essential driver of the socioeconomic cost of hip fracture care. METHODS: We analysed 21,819 cases in the Irish Hip Fracture Database from 2013 to 2019. Descriptive and analytical statistics were conducted. RESULTS: 29% (n = 6476) of patients were DDH during the study period. On multivariate analysis, the odds of DDH decreased as age increased (OR 0.28, p < 0.01, 95% CI 0.24-0.34). Patients who were independently mobile prior to fracture were 47% more likely to be DDH (OR 1.47, p < 0.01, 95% CI 1.29-1.68). Those mobilised early post operatively were 24% more likely to be DDH (OR 1.24, p < 0.01, 95% CI 1.06-1.45). Patients who waited > 72 h prior to surgery were 30% less likely to be DDH (OR 0.70, p < 0.01, 95% CI 0.56-0.88). CONCLUSION: The authors identified patient characteristics that increased the likelihood of DDH, i.e., younger patients independently mobile prior to fracture, who received timely surgery and early post-operative mobilisation. The Irish Hip Fracture Standards (IHFS) incorporate 2 out the 3 modifiable factors identified, which reinforces the importance of the IHFS in improving patient outcomes.

Study protocol for OptimalTTF-2: enhancing Tumor Treating Fields with skull remodeling surgery for first recurrence glioblastoma: a phase 2, multi-center, randomized, prospective, interventional trial.

BACKGROUND: OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention. METHODS: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up. DISCUSSION: New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020.

Cryoneurolysis' outcome on pain experience (COPE) in patients with low-back pain: study protocol for a single-blinded randomized controlled trial.

BACKGROUND: Low-back pain, including facet joint pain, accounts for up to 20 % of all sick leaves in DenmarkA proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome. METHODS: A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity ≥ 50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is the patients' impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are a reduction in low-back pain intensity (numeric rating scale) and quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory). Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months (T6). DISCUSSION: This study will provide information on the effectiveness of cryoneurolysis vs. the effectiveness of radiofrequency ablation or placebo for patients with facet joint pain, and help to establish whether cryoneurolysis should be implemented in clinical practice for this patient population. TRIAL REGISTRATION: The trial is approved by the ethical committee of Central Jutland Denmark with registration number 1-10-72-27-19 and the Danish Data Protection Agency with registration number 666,852. The study is registered at Clinicaltrial.gov with the ID number NCT04786145 .

Postoperative pressure injuries in adults having surgery under general anaesthesia: systematic review of perioperative risk factors.

BACKGROUND: Pressure injuries (PIs) after surgery affect thousands of people worldwide. Their management is expensive, a cost that can be reduced with proper preventive measures. Patients having surgery under general anaesthesia are at risk of developing PI, yet no specific tool has been developed to assess the risk in these patients. This review aimed to summarize the published data on perioperative risk factors associated with the development of PI in adults having surgery under general anaesthesia. METHODS: All studies reporting on risk factors associated with the development of PI were included. Data were extracted from all articles and meta-analysis was performed when three or more studies reported on a specific variable. RESULTS: The analysis identified five factors significantly associated with the development of PIs: cardiovascular disease, respiratory disease, diabetes mellitus, low haemoglobin level and longer duration of surgery. Factors not associated included serum albumin concentration, use of vasopressors during surgery, use of corticosteroids, sex and age. CONCLUSION: Cardiovascular disease, respiratory disease, diabetes mellitus, anaemia and duration of surgery should be taken into consideration when trying to identify surgical patients at high risk of developing PIs. These factors could be used to predict PIs after surgery.

ANTECEDENTES: Las úlceras por presión (pressure injuries, PI) son un problema de salud importante que afecta a millones de personas en todo el mundo. El tratamiento de las PI conlleva un coste elevado, que podría reducirse con medidas preventivas adecuadas. Aunque los pacientes a los que se realiza una cirugía bajo anestesia general tienen un mayor riesgo de desarrollar PI, no se han creado herramientas específicas para evaluar su riesgo. El objetivo de este trabajo es resumir los datos disponibles acerca de los factores de riesgo perioperatorios asociados al desarrollo de PI en pacientes adultos en los que se realiza un procedimiento quirúrgico bajo anestesia general. Un mejor conocimiento de los factores de riesgo de las PI podría permitir la estratificación de los pacientes antes de la cirugía y establecer mecanismos de prevención específicos. Número de registro Prospero CRD42019111877. MÉTODOS: Se incluyeron todos los estudios que analizaron los factores de riesgo asociados a las PI. Se obtuvieron los datos de todos los artículos y se realizó un metaanálisis cuando tres o más estudios presentaban información de una determinada variable. RESULTADOS: El análisis identificó cinco factores estadísticamente significativos asociados con el desarrollo de PI: enfermedad cardiovascular, enfermedad respiratoria, diabetes mellitus, mayor duración de la cirugía y hemoglobina baja. No se asociaron factores como la s-albúmina, la utilización de vasopresores durante la cirugía, el uso de corticoides, el sexo o la edad. CONCLUSIÓN: Se recomienda tener en cuenta la existencia de enfermedades cardiovasculares o respiratorias, diabetes mellitus, niveles bajos de hemoglobina y la duración de la cirugía a la hora de identificar a los pacientes quirúrgicos con riesgo elevado de desarrollar PI.

Emergency laparotomy research methodology: A systematic review.

BACKGROUND: Emergency abdominal surgery is associated with poorer clinical outcomes than similar procedures in the elective setting. Research into emergency laparotomy (EL) care is moving from observational studies which simply measure EL outcomes to interventional research evaluating the implementation of care strategies designed to improve the quality and outcomes from EL care. There is no consensus as to the optimal approach to conducting research in this sphere. The primary objective of this review was to examine how mortality and other outcome measures were reported in previous EL research and to identify what might be the most appropriate methods in future outcome research. METHODS: A systematic review was performed in accordance with the PRISMA principles. Electronic databases were interrogated with a pre-specified search strategy to identify English language studies addressing outcomes from EL care. Retrieved papers were screened and assessed according to pre-defined eligibility criteria. The mortality and other outcomes reported in each paper were extracted and examined. RESULTS: 16 studies were included. They demonstrated significant heterogeneity in case definition, outcome reporting and data processing. A wide range of mortality and other outcome measures were applied and reported. Only few studies included on patient-reported outcomes measures. CONCLUSION: The heterogeneity in EL research, demonstrated by this review must be considered when EL outcomes are compared. A standardized approach with respect to case definition, outcome measurement, and data analysis would provide for more valid and comparable evaluation of EL outcomes. Future EL research should include more patient centred outcomes.

ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib.

OBJECTIVE: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases. MATERIALS AND METHODS: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH. RESULTS: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC+/FISH+) and 16 discordant (ALK IHC+/FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR=4.5; 95% CI= 1.2-15.9; p=0.010. CONCLUSION: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.

Adipose-derived regenerative cells and fat grafting for treating breast cancer-related lymphedema: Lymphoscintigraphic evaluation with 1 year of follow-up.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a feared late complication. Treatment options are lacking at present. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with adipose-derived regenerative cells (ADRCs) for treating BCRL with 1 year of follow-up. MATERIAL AND METHODS: We included 10 patients with BCRL. ADRCs were injected directly into the axillary region together with a scar-releasing fat grafting procedure. Primary endpoint was change in arm volume. Secondary endpoints were change in patient-reported outcomes, changes in lymph flow, and safety. RESULTS: During follow-up, no significant change in volume was noted. Patient-reported outcomes improved significantly with time. Five patients reduced their use of conservative management. Quantitative lymphoscintigraphy did not improve on the lymphedema-affected arms. ADRCs were well tolerated, and only minor transient adverse events related to liposuction were noted. CONCLUSIONS: In this pilot study, a single injection of ADRCs improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events during the follow-up period. Lymphoscintigraphic evaluation showed no improvement after ADRC treatment. There was no change in excess arm volume. Results of this trial need to be confirmed in randomized clinical trials.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Mindfulness-based cognitive therapy (MBCT) is cost-effective compared to a wait-list control for persistent pain in women treated for primary breast cancer-Results from a randomized controlled trial.

OBJECTIVE: To investigate the cost-effectiveness of mindfulness-based cognitive therapy (MBCT) compared to a wait-list control group for pain in women treated for breast cancer. METHODS: A total of 129 women were randomly allocated to MBCT or a wait-list control group. The primary outcome was the minimal clinically important difference (MCID) on pain intensity (≥2 point reduction on an 11-point Numeric Rating Scale). Analyses were conducted from the health care system perspective and included data on health care utilization and pain medication retrieved from national registries for the period from baseline (T1) to 6 months postintervention (T4). Bootstrap simulations were used to estimate confidence intervals for the incremental cost and effect measures, and cost-effectiveness acceptability curves. In sensitivity analyses, we replaced dropouts with last-observation-carried-forward and tested consequences of higher costs of the intervention. RESULTS: The intervention cost was 240€ per participant. The average total cost from T1 to T4 in the MBCT group was 1706€ compared with 2436€ in the control group (mean difference: 729€, P = .07). More women in the MBCT group (N:19/36; 52.8%) than in the control group (N:14/48; 29.2%) achieved an MCID in pain intensity (OR=2.71, P = .03). The MBCT was cost-effective with a probability of 85% with a value of an additional women achieving MCID set to zero remained cost-effective with a probability of 70% to 82% when smaller effect and higher MBCT costs were assumed. CONCLUSIONS: Our results suggest that MBCT is a cost-effective pain intervention for women treated for breast cancer. Future studies could include utility measures, indirect costs, and active control groups to increase the generalizability and pragmatic value of the results.

The clinical safety, biodistribution and internal radiation dosimetry of [18F]AH113804 in healthy adult volunteers.

BACKGROUND: Quantitative biodistribution, venous blood and excretion data have been obtained following the intravenous bolus injection of AH113804 (18F) Injection in six healthy volunteers (HVs), four males and two females, up to approximately 5 h post-injection. For each subject, key organs and tissues were delineated and analytical fits were made to the image data as functions of time to yield the normalised cumulated activities. These were input to an internal radiation dosimetry calculation based upon the Medical Internal Radiation Dose (MIRD) schema for the Cristy-Eckerman adult male or female phantom. The absorbed doses per unit administered activity to the 24 MIRD-specified target organs were evaluated for an assumed 3.5-h urinary bladder voiding interval using the Organ Level INternal Dose Assessment/Exponential Modelling (OLINDA/EXM) code. The sex-specific absorbed doses were then averaged, and the effective dose per unit administered activity was calculated. RESULTS: Excluding the remaining tissue category, the three source regions with the highest mean initial 18F activity uptake were the liver (18.3%), lung (5.1%) and kidney (4.5%) and the highest mean normalised cumulated activities were the urinary bladder contents and voided urine (1.057 MBq h/MBq), liver (0.129 MBq h/MBq) and kidneys (0.065 MBq h/MBq). The three organs/tissues with the highest mean sex-averaged absorbed doses per unit administered activity were the urinary bladder wall (0.351 mGy/MBq), kidneys (0.052 mGy/MBq) and uterus (0.031 mGy/MBq). CONCLUSIONS: AH113804 (18F) Injection was safe and well tolerated. Although the effective dose, 0.0298 mSv/MBq, is slightly greater than for other common 18F PET imaging radiopharmaceuticals, the biodistribution and radiation dosimetry profile remain favourable for clinical PET imaging.

Meta-analysis of negative-pressure wound therapy for closed surgical incisions.

BACKGROUND: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions. METHODS: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions. RESULTS: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0·54, 95 per cent c.i. 0·33 to 0·89) and seroma formation (RR 0·48, 0·27 to 0·84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence. CONCLUSION: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet.

Moving towards personalised therapy in head and neck squamous cell carcinoma through analysis of next generation sequencing data.

Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases to identify the most common molecular alterations in HNSCC. The importance of these genetic discoveries is reviewed and how they may be incorporated into clinical care decisions is discussed. Considerations for the role of genetic stratification in the clinical management of head and neck cancer are maturing rapidly and can be improved by integrating data sets. This article is meant to summarise the discoveries made using multiple genomic platforms so that the head and neck cancer care provider can apply these discoveries to improve clinical care.

Effectiveness of the "Cancer Home-Life Intervention" on everyday activities and quality of life in people with advanced cancer living at home: a randomised controlled trial and an economic evaluation.

BACKGROUND: During the past decade an increasing number of people live with advanced cancer mainly due to improved medical treatment. Research has shown that many people with advanced cancer have problems with everyday activities, which have negative impact on their quality of life, and that they spend a considerable part of their time at home. Still, research on interventions to support the performance of and participation in everyday activities is only scarcely available. Therefore, the occupational therapy-based "Cancer Home-Life Intervention" consisting of tailored adaptive interventions applied in the participant's home environment was developed. The objective of this study is to examine the effectiveness and cost-effectiveness of the Cancer Home-Life Intervention compared to usual care on the performance of and participation in everyday activities and quality of life in people with advanced cancer living at home. METHODS: The study is a randomised, controlled trial (RCT) including an economic evaluation. The required sample size of 272 adults living at home will be recruited from outpatient clinics at two Danish hospitals. They should be diagnosed with cancer; evaluated incurable by the responsible oncologist; and with a functional level 1-2 on the WHO performance scale. The primary outcome is the quality of performance of activities of daily living. Secondary outcomes are problems with prioritised everyday activities; autonomy and participation; and health-related quality of life. Participants are randomly assigned to: a) The Cancer Home-Life Intervention in addition to usual care, and b) Usual care alone. DISCUSSION: The trial will show whether the Cancer Home-Life Intervention provides better support for people with advanced cancer living at home in performing and participating in everyday activities, and whether it contributes to their health-related quality of life. The economic evaluation alongside the RCT will show if the Cancer Home-Life Intervention is cost-effective. The trial will also show the acceptability of the intervention to the target group, and whether subgroups of participants will benefit more than others. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02356627. Registered 02/02/2015.

Validation of 3 T MRI including diffusion-weighted imaging for nodal staging of newly diagnosed intermediate- and high-risk prostate cancer.

AIM: To prospectively validate 3 T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. MATERIALS AND METHODS: Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3 T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. RESULTS: A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p=0.017), with larger diameter (mean 12.3 versus 5.2 mm, p=0.048) and fewer were treated with curative intent (six versus nine, p=0.03), compared with the false-negative group. CONCLUSION: MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

Randomized trial to examine procedure-to-procedure transfer in laparoscopic simulator training.

BACKGROUND: Laparoscopic simulation has become a standard component of surgical training, but there is limited knowledge regarding skills transfer between procedural tasks. The objective was to investigate the specificity of procedural simulator training. METHODS: This was randomized single-centre educational superiority trial. Surgical novices practised basic skills on a laparoscopic virtual reality simulator. On reaching proficiency, participants were randomized to proficiency-based training. The intervention group practised two procedures on the simulator (appendicectomy followed by salpingectomy), whereas the control group trained on only one procedure (salpingectomy). The main outcomes were number of repetitions and time to proficiency for the second procedure. RESULTS: Ninety-six participants were randomized, of whom 74 per cent were women, with a median age of 26 years. The intervention group needed significantly fewer attempts than the control group to reach proficiency in the second procedure: median (i.q.r.) 22 (17-34) versus 32 (26-41) attempts, which corresponded to 24·1 per cent fewer attempts as assessed by multivariable analysis (P = 0·004). The intervention group required significantly less time than the control group to reach proficiency: median (i.q.r.) 88 (63-127) versus 131 (101-153) min respectively, corresponding to a difference of 31·1 min as assessed by multivariable analysis (P = 0·001). CONCLUSION: Practising two procedures, compared with only one, reduced the number of attempts and time to reach proficiency in the second procedure. Skills transfer is seen between two tasks in laparoscopic simulator training; however, task specificity is still present when practising procedures. REGISTRATION NUMBER: NCT02069951 (http://www.clinicaltrials.gov).

Oral Debio1143 (AT406), an antagonist of inhibitor of apoptosis proteins, combined with daunorubicin and cytarabine in patients with poor-risk acute myeloid leukemia--results of a phase I dose-escalation study.

BACKGROUND: Treatment of acute myeloid leukemia (AML) remains difficult owing to the development of treatment resistance, which might be overcome through antagonists of inhibitors of apoptosis proteins (IAPs). PATIENTS AND METHODS: The present multicenter, open-label, dose-escalation study aimed to evaluate the tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of Debio1143 (formerly AT-406), a new IAP antagonist, when given along with a standard "7 plus 3 regimen" of daunorubicin and cytarabine to poor-risk patients with AML during the induction cycle. Consecutive patient cohorts received once-daily 100, 200, 300, or 400 mg of oral Debio1143 on treatment days 1 to 5. Blood samples were collected regularly until hematologic recovery or response was documented. Bone marrow samples were collected on days 0, 14, and 29 and PK and PD samples on days 1, 3, 5, 8, and 10 and 1, 2, and 8, respectively. RESULTS: Of the 29 enrolled patients, 23 completed the study. The most common adverse events of any grade deemed related to treatment were nausea (31% of patients), diarrhea (14%), and febrile neutropenia (14%). Exposure exceeded dose proportionality, without accumulation over 5 days. Inhibition of cellular IAP1 was detectable in the CD34/CD117(+) cells and blasts. A total of 11 patients (38%) achieved complete remission, most in the 100-mg dose cohort. Of these, 6 (56%) developed a relapse within the study period. The patients with a response more frequently showed plasma increases of tumor necrosis factor-α and interleukin-8 after the first dose of Debio1143. CONCLUSION: Debio1143 ≤ 400 mg/d showed good tolerability in combination with daunorubicin and cytarabine. Additional studies in subsets of patients with AML are warranted.