Adverse events in the placebo arm of maintenance therapy trials in advanced ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Maintenance treatment is standard of care for front-line (FL) and platinum-sensitive recurrent ovarian cancer (PSROC) following response to chemotherapy. Adverse events (AEs) on maintenance therapies are common and usually attributable to investigational treatments but could also be unrelated. Randomised controlled trial (RCT) with blinded placebo design is the gold standard for determining the relative differences in efficacy and AEs between treatment arms. We performed a meta-analysis to quantify AE rates in placebo arms of RCTs to determine AEs not due to investigational agents. METHODS: We performed an electronic search to identify eligible RCTs in FL and PSROC settings. Data from placebo arms were extracted and pooled using the inverse variance method to determine the risk of any AE, overall and specific grade 3 or higher (G ≥ 3) AEs, and AE-related treatment delay, reduction and discontinuation. RESULTS: We identified 13 eligible RCTs (FL, N = 8; PSROC, N = 5) with 2224 patients who received placebo (FL, N = 1541; PSROC, N = 683). The majority experienced an AE of any grade (FL, 93.0%; PSROC, 95.2%). Substantial proportions experienced G ≥ 3 AEs (FL, 14.6%; PSROC, 18.2%). In the FL setting, AEs led to treatment delay in 14.4%, dose reduction in 4.1% and discontinuation in 2.6%. Findings were similar for PSROC: 8.4%, 5.5% and 2.1%, respectively. CONCLUSIONS: AEs not due to investigational agents are common in ovarian cancer patients in maintenance therapy RCTs. Potential explanations include the nocebo effect, residual toxicities from previous treatment or underlying disease. Further research is required to identify better approaches to assessing AEs in this population.

Reporting the trajectories of adverse events over the entire treatment course in patients with recurrent platinum-sensitive ovarian cancer treated with platinum-based combination chemotherapy regimens: A graphical approach to trial adverse event reporting.

BACKGROUND: Clinical trials report adverse events (AEs) in a dense table focusing on the frequency of 'worst grade' AEs experienced over the duration of treatment. There is usually no granular information provided on the timing and trajectory of AEs or whether they are likely to worsen, improve, or remain constant over time. PATIENTS AND METHODS: Non-hematologic (NH) AE data was extracted from the CALYPSO trial comparing carboplatin with pegylated liposomal doxorubicin (CD) to carboplatin with paclitaxel (CP) in recurrent ovarian cancer (ROC). Generalised estimating equations (GEE) were used to assess the risk and trajectory of combined Grade 2 or higher (G2+) AE and of each specific AE. The risk of G2+AE was also compared between treatment arms. RESULTS: The study included 976 patients and AE were reported for the duration of treatment. Most patients experienced at least one G2+NHAE (CP:CD, 96.0%:80.6%). Risk of combined G2+AE increased with CP (4.1% per-cycle) but decreased with CD (0.8%, P <0.01). When alopecia and sensory neuropathy were excluded, risk of G2+ AE decreased by 2.7% per-cycle, with no significant difference between treatment arms. G2+ nausea improved (15.2% per-cycle, P <0.01). G2+ sensory neuropathy worsened (29.3% per-cycle, P <0.01). Fatigue was stable (17% per-cycle, P =0.06) whilst G2+ pain decreased over time (13.4% per-cycle, P <0.01), with no difference between treatment arms. CONCLUSION: Existing trial data can be used to provide AE trajectories as illustrated here for ROC. These trajectories have utility in guiding treatment choice and potentially optimising AE management with novel therapies and treatment combinations.

Triangle of Marcille: the anatomical gateway to lateral pelvic exenteration.

BACKGROUND: To perform more radical surgery for complex pelvic malignancies and recurrent colorectal cancer, the surgeon must increasingly operate outside the conventional anatomical planes. Published in 1963 the 'Triangle of Marcille' (lumbosacral triangle) remained primarily of intellectual interest being found lateral to the traditional operating field. However, with the advancement of complex colorectal and gynaecological surgery it now provides a schema to assist surgeons in becoming acquainted with a complex and poorly understood anatomical region. Additionally, it prepares the surgeon for the extent of lateral dissection required to achieve the 'holy grail' for oncological surgery in pelvic malignancy, the complete resection (R0). METHODS: To prosect a preserved cadaver in order to demonstrate, in vivo, the contents and borders of the Triangle of Marcille for the purposes of teaching surgeons and future surgeons. RESULTS: The Triangle of Marcille is both described and demonstrated in vivo, illustrated with diagrams and photographs. The importance of this region to the surgical management of complex colorectal and gynaecological surgery is discussed. CONCLUSION: The Triangle of Marcille is a vital anatomical region for advanced pelvic surgery, particularly in the current era of pelvic exenteration, and especially for those that include the lateral pelvic compartment.

Utilisation of a Novel Test to Measure Severity and Treatment Efficacy of Posterior Blepharitis.

Background. This study evaluated the effectiveness of managing posterior blepharitis (PB) using a novel Posterior Blepharitis Management Protocol (PBMP). Design. Prospective, consecutive case series with 100% followup to one month. Participants. 27 patients (54 eyes) with PB from an Ophthalmology practice in Sydney, Australia. Methods. Each patient's PB was assessed by grading the nature and expressibility of the central lower lid tarsal gland secretions on Compression Of The Eyelid (COTE). Patients were then instructed in detail to undertake daily PB management sessions at home using our modified PBMP. Main Outcome Measures. On a subjective scale, patients compared their symptoms at one month with baseline. COTE scores were reevaluated to assess the objective effectiveness of each individual's PBMP. COTE scoring was described as grades 1 (clear oil), 2 (pus, liquid), 3 (toothpaste-like secretions), and 4 (complete tarsal gland obstruction). Results. Patients reported a mean 77.8% ± 13.5% subjective improvement in symptoms. There was a trend towards improvement in COTE grading at one month compared with baseline: grades 1 (0 to 7.4%), 2a (22.2 to 16.6%), 2b (7.4 to 3.7%), 3 (18.5 to 27.7%), and 4 (51.8 to 44%). Conclusions. PBMP provided a rapid, inexpensive, simple, effective, and safe method of treating PB.

Microwash or macrowash technique to maintain a clear cornea during cataract surgery.

We describe a technique of irrigating and thereby rapidly and effectively clearing the cornea of relatively large amounts of surface contaminants that reduce surgical visibility and may contribute to endophthalmitis. This technique is referred to as "macrowash." If the technique is required, it is usually at the commencement of cataract surgery, immediately after placement of the surgical drape. The technique not only saves time, but also reduces the volume of irrigating solution required by the "microwash" technique, which is traditionally carried out by the scrub nurse/surgical assistant using a Rycroft cannula attached to a 15 mL container of irrigating solution.