Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.     

Cross‐country evidence on the social determinants of the post‐socialist mortality crisis in Europe: a review and performance‐based hierarchy of variables

An unprecedented mortality crisis befell the former socialist countries between 1989 and 1995, representing one of the greatest demographic shocks of the period after the Second World War. While it is likely that country‐level variation in the post‐socialist mortality crisis in Eastern Europe can be explained by a constellation of political and socio‐economic factors, no comprehensive review of the existing scholarly attempts at explaining these factors exists. We review 39 cross‐national multi‐variable peer reviewed studies of social determinants of mortality in post‐socialist Europe in order to assess the social factors behind the post‐socialist mortality crisis, determine the gaps in the existing literature and to make suggestions for future research. We propose a novel methodology to determine the relative importance of variables based on the ratio of significant to insignificant findings for each variable. The literature identifies inequality, welfare payments, religious composition, democracy, economic performance and unemployment as the leading factors that have a significant influence on mortality outcomes. Existing cross‐country studies fail to establish a definitive connection between mortality and diets, drinking patterns, liberalisation, trust, health expenditure and war. We also point out that the level of analysis is not a neutral methodological choice but might influence the results themselves.     

An open-label,prospective, randomized,controlled, multicenter,phase 1b study of StrataGraft skin tissue versus autografting in patients with deep partial-thickness thermal burns

ObjectiveThis open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns.MethodsThirty subjects with DPT thermal burns (3%–43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm² refrigerated tissue; cohort 2, ≤440 cm² refrigerated tissue; and cohort 3, ≤440 cm² cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months.ResultsBy Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%).ConclusionsStrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated.     

Ascertaining Design Requirements for Postoperative Care Transition Interventions

Background  Handoffs or care transitions from the operating room (OR) to intensive care unit (ICU) are fragmented and vulnerable to communication errors. Although protocols and checklists for standardization help reduce errors, such interventions suffer from limited sustainability. An unexplored aspect is the potential role of developing personalized postoperative transition interventions using artificial intelligence (AI)-generated risks. Objectives  This study was aimed to (1) identify factors affecting sustainability of handoff standardization, (2) utilize a human-centered approach to develop design ideas and prototyping requirements for a sustainable handoff intervention, and (3) explore the potential role for AI risk assessment during handoffs. Methods  We conducted four design workshops with 24 participants representing OR and ICU teams at a large medical academic center. Data collection phases were (1) open-ended questions, (2) closed card sorting of handoff information elements, and (3) scenario-based design ideation and prototyping for a handoff intervention. Data were analyzed using thematic analysis. Card sorts were further tallied to characterize handoff information elements as core, flexible, or unnecessary. Results  Limited protocol awareness among clinicians and lack of an interdisciplinary electronic health record (EHR)-integrated handoff intervention prevented long-term sustainability of handoff standardization. Clinicians argued for a handoff intervention comprised of core elements (included for all patients) and flexible elements (tailored by patient condition and risks). They also identified unnecessary elements that could be omitted during handoffs. Similarities and differences in handoff intervention requirements among physicians and nurses were noted; in particular, clinicians expressed divergent views on the role of AI-generated postoperative risks. Conclusion  Current postoperative handoff interventions focus largely on standardization of information transfer and handoff processes. Our design approach allowed us to visualize accurate models of user expectations for effective interdisciplinary communication. Insights from this study point toward EHR-integrated, “flexibly standardized” care transition interventions that can automatically generate a patient-centered summary and risk-based report. Keyword: continuity of care, care transition, requirements analysis and design, handoffs, surgery, anesthesia, intensive and critical care, machine learning     

Evaluating the influence of prostate-specific antigen kinetics on metastasis in men with PSA recurrence after partial gland therapy

Purpose

Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir + 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy.

Clinical Evaluation of Deep Learning and Atlas-Based Auto-Contouring of Bladder and Rectum for Prostate Radiation Therapy

PurposeAuto-contouring may reduce workload, interobserver variation, and time associated with manual contouring of organs at risk. Manual contouring remains the standard due in part to uncertainty around the time and workload savings after accounting for the review and editing of auto-contours. This preliminary study compares a standard manual contouring workflow with 2 auto-contouring workflows (atlas and deep learning) for contouring the bladder and rectum in patients with prostate cancer.Methods and MaterialsThree contouring workflows were defined based on the initial contour-generation method including manual (MAN), atlas-based auto-contour (ATLAS), and deep-learning auto-contour (DEEP). For each workflow, initial contour generation was retrospectively performed on 15 patients with prostate cancer. Then, radiation oncologists (ROs) edited each contour while blinded to the manner in which the initial contour was generated. Workflows were compared by time (both in initial contour generation and in RO editing), contour similarity, and dosimetric evaluation.ResultsMean durations for initial contour generation were 10.9 min, 1.4 min, and 1.2 min for MAN, DEEP, and ATLAS, respectively. Initial DEEP contours were more geometrically similar to initial MAN contours. Mean durations of the RO editing steps for MAN, DEEP, and ATLAS contours were 4.1 min, 4.7 min, and 10.2 min, respectively. The geometric extent of RO edits was consistently larger for ATLAS contours compared with MAN and DEEP. No differences in clinically relevant dose-volume metrics were observed between workflows.ConclusionAuto-contouring software affords time savings for initial contour generation; however, it is important to also quantify workload changes at the RO editing step. Using deep-learning auto-contouring for bladder and rectum contour generation reduced contouring time without negatively affecting RO editing times, contour geometry, or clinically relevant dose–volume metrics. This work contributes to growing evidence that deep-learning methods are a clinically viable solution for organ-at-risk contouring in radiation therapy.     

Open hemiarch versus clamped ascending aorta replacement for aortopathy during initial bicuspid aortic valve replacement

BackgroundThere is controversy regarding the extent of aortic resection necessary in patients with aortopathy related to bicuspid aortic valve disease. To address this issue, we reviewed our experience in patients undergoing ascending aorta replacement during bicuspid aortic valve replacement.MethodsWe reviewed 702 patients who underwent ascending aorta replacement at the time of initial nonemergent native bicuspid aortic valve replacement at our institution between January 2000 and June 2017. Treatment cohorts included an open hemiarch replacement group (n = 225; 32%) and a clamped ascending aorta replacement group (n = 477; 68%).ResultsMedian patient age was 60 years (interquartile range [IQR], 51-67 years), female sex was present in 113 patients (16%), ejection fraction was 62% (IQR, 56%-66%), and aortic arch diameter was 33 mm (IQR, 29-36 mm). Cardiopulmonary bypass time was longer in the hemiarch replacement group (188 minutes vs 97 minutes; P < .001). Procedure-related complications (36%) and mortality (<1%) were similar in the 2 groups; however, the hemiarch group had an increased odds of blood transfusion (odds ratio, 1.62; 95% confidence interval [CI], 1.15-2.28; P = .006). The median duration of follow-up was 6.0 years (95% CI, 5.3-6.8 years). Overall survival was 94 ± 1% at 5 years and 80 ± 2% at 10 years. Multivariable analysis demonstrated similar survival in the 2 groups (hazard ratio, 0.83; 95% CI, 0.51-1.33; P = .439). No repeat aortic arch operations were done for aortopathy over the duration of clinical follow-up.ConclusionsCompared with patients in the clamped ascending aorta replacement group, patients in the hemi-arch replacement group had longer cardiopulmonary bypass and aortic cross-clamp times, along with an increased risk of blood transfusion, but similar freedom from repeat aortic arch operation and survival. We identified no advantage of performing hemiarch replacement in the absence of aortic arch dilation.     

Trends in the incidence of fetal macrosomia and its phenotypes in the United States, 1971–2017

Archives of Gynecology and Obstetrics - Studies have reported a surge in the prevalence of obesity among various demographic groups including pregnant women in the U.S. Given the association...