Robot Assisted Surgical Ward Rounds: Virtually Always There.

BACKGROUND:  While an explosion in technological sophistication has revolutionized surgery within the operating theatre, delivery of surgical ward-based care has seen little innovation.  Use of telepresence allowing off-site clinicians communicate with patients has been largely restricted to outpatient settings or use of complex, expensive, static devices.  We designed a prospective study to ascertain feasibility and face validity of a remotely controlled mobile audiovisual drone (LUCY) to access inpatients.  This device is, uniquely, lightweight, freely mobile and emulates 'human' interaction by swiveling and adjusting height to patients' eye-level.   METHODS: Robot-assisted ward rounds(RASWR) were conducted over 3 months. A remotely located consultant surgeon communicated with patients/bedside teams via encrypted audiovisual telepresence robot (DoubleRoboticstm, California USA).  Likert-scale satisfaction questionnaires, incorporating free-text sections for mixed-methods data collection, were disseminated to patient and staff volunteers following RASWRs.  The same cohort completed a linked questionnaire following conventional (gold-standard) rounds, acting as control group. Data were paired, and non-parametric analysis performed.  RESULTS: RASWRs are feasible (>90% completed without technical difficulty). The RASWR(n=52 observations) demonstrated face validity with strong correlations (r>0.7; Spearman, p-value <0.05) between robotic and conventional ward rounds among patients and staff on core themes, including dignity/confidentiality/communication/satisfaction with management plan. Patients (96.08%, n=25) agreed RASWR were a satisfactory alternative when consultant physical presence was not possible. There was acceptance of nursing/NCHD cohort (100% (n=11) willing to regularly partake in RASWR).  CONCLUSION: RASWRs receive high levels of patient and staff acceptance, and offer a valid alternative to conventional ward rounds when a consultant cannot be physically present.

Phase I safety, pharmacokinetic, and pharmacogenomic trial of ES-285, a novel marine cytotoxic agent, administered to adult patients with advanced solid tumors.

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, pharmacogenomics, and efficacy of ES-285, a novel agent isolated from a marine mollusc, in adult cancer patients. Patients received a 24-hour i.v. infusion of ES-285 once every 3 weeks until disease progression or unacceptable toxicity. The starting dose was 4 mg/m(2). Dose escalation in cohorts of at least three patients proceeded according to the worst toxicity observed in the previous cohort. Twenty-eight patients were treated with 72 courses of ES-285 across eight dose levels. No dose-limiting toxicities were seen between 4 and 128 mg/m(2). Two of four patients treated at 256 mg/m(2) had dose-limiting reversible grade 3 transaminitis; one patient at 256 mg/m(2) also had transient grade 3 central neurotoxicity. One of three patients subsequently treated at 200 mg/m(2) died following drug-related central neurotoxicity. Other toxicities included phlebitis, nausea, fatigue, and fever. Pharmacokinetic studies indicated dose proportionality with high volume of distribution (median V(ss) at 256 mg/m(2) was 2,389 liters; range, 1,615-4,051 liters) and long elimination half life (median t(1/2) at 256 mg/m(2) was 28 h; range, 21-32 h). The three patients with dose-limiting toxicity had the highest drug exposure. Pharmacogenomic studies of paired surrogate tissue samples identified changes in gene expression following treatment that correlated with increasing dose. Disease stabilization for 6 to 18 weeks was recorded in nine patients. Using this schedule, 128 mg/m(2) was considered safe and feasible. At this dose, pharmacologically relevant concentrations of the drug were safely achieved with pharmacogenomic studies indicating changes in the expression of genes of potential mechanistic relevance.

Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors.

PURPOSE: The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine) induces DNA demethylation and re-expression of epigenetically silenced genes, and increases carboplatin sensitivity of tumor xenograft models. We designed a clinical study to determine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be capable of producing equivalent biologic effects in patients with solid tumors. PATIENTS AND METHODS: In a two-stage design, 33 patients received escalating doses of decitabine administered as a 6-hour infusion on day 1 followed by carboplatin, area under the concentration-time curve (AUC) 5 (cohort 1) and AUC 6 (cohort 2), on day 8 of a 28-day cycle. Pharmacodynamic analyses included 5-methyl-2'-deoxycytidine levels, MAGE1A CpG island methylation, and fetal hemoglobin (HbF) expression. RESULTS: The major toxicity was myelosuppression. Dose limiting toxicities, prolonged grade 4 neutropenia (one patient), and sepsis and grade 3 anorexia/fatigue (one patient), were seen in two of four patients treated with decitabine 135 mg/m2 and carboplatin AUC 5. Dose limiting toxicity comprising neutropenic sepsis (one patient) and grade 3 fatigue (one patient) was seen in two of 10 patients treated at decitabine 90 mg/m2 and carboplatin AUC 6. Decitabine induced dose-dependent, reversible demethylation in peripheral-blood cells (PBCs) maximally at day 10. Furthermore, decitabine 90 mg/m2 induced demethylation of the MAGE1A CpG island in PBCs, buccal cells, and tumor biopsies, as well as elevation of HbF expression. CONCLUSION: Decitabine can be combined safely with carboplatin at a dose and schedule that causes epigenetic changes equivalent to or greater than that observed in mice with carboplatin-sensitized xenografts. The recommended dose/schedule for phase II trials is decitabine 90 mg/m2 (day 1) followed by carboplatin AUC 6 (day 8) every 28 days.