Window of opportunity treatment in breast cancer

Window of opportunity therapies, which involve short‐term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone‐receptor positive breast cancer, a 2‐week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision‐making regarding treatment options. Changes in short‐term biomarker endpoints such as cell proliferation measured by Ki‐67 can act as surrogate markers of long‐term outcomes. Paired tissues obtained pre‐ and post‐investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.     

Standard preoperative use of nonopioid multi‐modal medications for patients undergoing mastectomy with immediate reconstruction and the effect on postoperative opioid needs

Standardized nonopioid preoperative protocol effects perioperative opioids. Combined use of acetaminophen, pregabalin, celecoxib, and transdermal scopolamine (APCS), in mastectomy with immediate subpectoral reconstruction procedures. Retrospective (2014‐2017) cohort study (n = 305) examined treatment groups; APCS, no treatment (NONE), and partial combination APCS (OTHER), employing multivariable gamma regression models controlling preoperative and perioperative variables, examining postoperative opioid use (oral morphine equivalents, OME) and hospital stay (hours, LOS). APCS group had a 25% statistical reduction in OME total vs OTHER, a 12% statistical reduction in LOS vs OTHER, and 11% statistical reduction in LOS vs NONE. Standardized nonopioid preoperative protocol provides insight into perioperative opioid use.     

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study)

Background

The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen.

Objective:

To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting.

Methods:

A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed.

Results:

Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of “red man syndrome”, and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400.

Conclusion:

The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.     

RCT of a promising vocational/employment program for high-risk juvenile offenders

Juvenile offenders with substance use problems are at high risk for deleterious long-term outcomes. This study evaluated the capacity of a promising vocational and employment training program in the building sector (i.e., Community Restitution Apprenticeship-Focused Training, CRAFT) to mitigate such outcomes through enhanced employment and education. Participants were 97 high-risk juvenile offenders (mean age = 15.8 years) randomized to CRAFT versus education as usual (EAU) intervention conditions. Multi-method procedures measured employment, education, substance use, mental health, and criminal outcomes through a 30-month post-baseline follow-up. CRAFT was significantly more effective than EAU at increasing rates of youth employment and GED attendance. Intervention effects were not observed, however, for months employed, hours worked, or hourly wage. Measures of youth substance use, mental health symptoms, and criminal activity showed no favorable or iatrogenic effects. The potential of CRAFT was modestly supported, and suggestions were made for future research.     

A Faculty Toolkit for Formative Assessment in Pharmacy Education

This paper aims to increase understanding and appreciation of formative assessment and its role in improving student outcomes and the instructional process, while educating faculty on formative techniques readily adaptable to various educational settings. Included are a definition of formative assessment and the distinction between formative and summative assessment. Various formative assessment strategies to evaluate student learning in classroom, laboratory, experiential, and interprofessional education settings are discussed. The role of reflective writing and portfolios, as well as the role of technology in formative assessment, are described. The paper also offers advice for formative assessment of faculty teaching. In conclusion, the authors emphasize the importance of creating a culture of assessment that embraces the concept of 360-degree assessment in both the development of a student’s ability to demonstrate achievement of educational outcomes and a faculty member’s ability to become an effective educator.     

Subjective Feelings of Alcohol Intoxication in Asians with Genetic Variations of ALDH2 Alleles

Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.     

The efficacy of intranasal fluticasone propionate in the relief of ocular symptoms associated with seasonal allergic rhinitis.

Intranasal corticosteroids have been shown to decrease ocular symptoms associated with allergic rhinitis as well as nasal symptoms. The primary objective of this retrospective analysis was to evaluate the efficacy of fluticasone propionate (FP) aqueous nasal spray in the treatment of ocular symptoms in patients with seasonal allergic rhinitis (SAR). We pooled efficacy data from seven multicenter, randomized, double-blind, placebo-controlled studies of similar design. Each study evaluated the efficacy of intranasal FP, 200 micrograms, given once daily in the treatment of nasal and ocular symptoms associated with SAR. At baseline and after 7 and 14 days of treatment, clinicians rated the severity of four individual ocular symptoms (itching, tearing, redness, and puffiness) via visual analog scales of 0-100, where 0 = no symptoms and 100 = worst symptoms. The four ratings were added to form the total ocular symptom score (TOSS). Patients rated the overall severity of their ocular symptoms (all symptoms evaluated with a single score) daily on diary cards in a similar fashion. The primary outcome was the mean change from baseline in the clinician-rated TOSS. A between-group difference of 25 points in the mean change from baseline TOSS by day 14 was considered clinically relevant. The FP group had greater mean changes from baseline in the TOSS and in all four individual symptom scores compared with placebo at days 7 and 14. At day 7, mean decreases from baseline in the TOSS were 76.0 points for the FP group and 50.9 points for the placebo group (p < 0.001), a difference between groups of 25.1. At day 14, mean decreases from baseline in the TOSS were 91.8 points for the FP group and 60.2 points for the placebo group (p < 0.001), a difference between groups of 31.6. Consistent with the clinician-rated data, patient-rated data showed a significantly greater reduction in the overall ocular symptom score for the FP group compared with placebo for both weeks 1 and 2 (p < 0.001). Intranasal FP provides safe and effective relief of ocular symptoms associated with SAR. Patients with allergic rhinitis who also have ocular symptoms as a component of their disease may benefit from intranasal FP monotherapy without the addition of topical ophthalmologic agents or oral antihistamines. Such an approach may have advantages regarding compliance and cost-effectiveness of treatment.