Laparoscopic management of ectopic pregnancy in the presence of a significant haemoperitoneum

Objective To assess the trend in the use of operative laparoscopy in the management of patients with ruptured ectopic pregnancy and significant haemoperitoneum. Method Four-year prospective observational study of the operative management of women with ruptured ectopic pregnancy and significant haemoperitoneum at the Whipps Cross University Hospital from January 2003 to December 2006. The inclusion criteria were patients with a clinical or laparoscopic assessment of significant haemoperitoneum (>800 ml). The amount of haemoperitoneum was determined at surgery. Results The blood loss ranged from 800 to 3,500 ml. The laparoscopic approach in this specific clinical scenario increased from 40% in 2003 to 100% in 2006. In 2003 there were five patients, two (40%) were treated by laparoscopy, one (20%) was converted from laparoscopy to laparotomy and two (40%) had laparotomy. In 2004 there were six patients, five (85%) underwent laparoscopic management and one (15%) had laparotomy. In 2005 we had 14 patients, ten (72%) had laparoscopic management, 2 (14%) were converted to laparotomy and 2 (14%) had laparotomies. There were12 patients in 2006 and all (100%) were treated by laparoscopy. Conclusion Our study demonstrates that with highly skilled anaesthetic and surgical teams, operative laparoscopy with its recognized advantages over laparotomy and is feasible in women with ruptured ectopic pregnancy and significant haemoperitoneum.     

Intraperitoneal chemotherapy for patients with advanced ovarian cancer: a review of the evidence and standards for the delivery of care

OBJECTIVES: To evaluate the role of intraperitoneal (IP) chemotherapy as part of primary treatment in patients with advanced ovarian cancer and to develop standards of care within the context of current clinical practice. METHODS: A multidisciplinary expert panel, convened to develop standards on the use of IP chemotherapy, searched the MEDLINE, EMBASE, and Cochrane Library databases up to December 2006 for randomized trials or published standards on the efficacy and/or delivery of IP chemotherapy. RESULTS: Eight randomized trials comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified. Three trials reported statistically significant improvements in median survival of 8.0, 11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9-month improvement in median overall survival (RR=0.75, 95% CI=0.58-0.97) represented a 25% reduction in the risk of death with IP chemotherapy. Severe adverse events and catheter-related complications were often dose limiting with IP chemotherapy. Using a consensus-based approach with a nationally representative panel, multidisciplinary care standards were developed to review medical and surgical criteria, the practice setting, volume requirements, and the institutional criteria required to safely deliver IP chemotherapy. CONCLUSION: The survival benefits with cisplatin-based IP chemotherapy may represent a significant improvement in the outlook for select patients with advanced ovarian cancer. The delivery of IP chemotherapy is more challenging than the IV route; however, severe adverse events and catheter-related complications may be offset through research defining the optimum treatment regimen, and the standardization of care. System-wide standards for the delivery of IP chemotherapy in Canada for patients with optimally debulked stage III ovarian cancer are offered.     

Strategic,feasibility, economic,and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.     

Transplanted human cones incorporate into the retina and function in a murine cone degeneration model

Once human photoreceptors die, they do not regenerate, thus, photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation, and synaptic connectivity to the host will be critical in advancing this technology for use in clinical practice. Unlike the unstructured grafts of prior cell-suspension transplantations into end-stage degeneration models, we describe the extensive incorporation of induced pluripotent stem cell (iPSC) retinal organoid–derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarization as well as the development of morphological features critical for light detection, namely the formation of inner and well-stacked outer segments oriented toward the retinal pigment epithelium. Putative synapse formation and graft function were evident at both structural and electrophysiological levels. Overall, these results show that human photoreceptors interacted readily with a partially degenerated retina. Moreover, incorporation into the host retina appeared to be beneficial to graft maturation, polarization, and function.     

Improved prediction of medical expenditures and health care utilization using an updated chronic disease score and claims data

ObjectiveTo predict future medical expenditures, health care utilization, and mortality in Switzerland using an updated chronic disease score (CDS), a chronic morbidity measure based on pharmacy data.Study Design and SettingWe performed a cohort study using medical claims data from insured persons enrolled in 2009 and 2010. Patient's characteristics, chronic conditions, and health care costs from baseline were used to calculate each patient's disease score. Two-part regression models were fit to predict health care expenditures, utilization, and mortality during the following year using the score's baseline values. We calculated the proportion of explained variation for each regression model to assess their performance.ResultsThe CDS model, controlled for sociodemographics and health insurance plan, showed a significant improvement in explained variance of health care costs, outpatient costs, and outpatient visits in 2010. Future outpatient visits were predicted best with an R² of 29.2% (age group: 18–65 years) and 22.9% (>65 years), and models predicted future mortality with a c-statistic of 0.8.ConclusionThe CDS showed reasonable predictive validity of future health care utilization and medical expenditure based on pharmacy dispensing data, which may support health care decision makers in the planning delivery systems and resource allocation.