Research Spotlight

Jones, V. E., K. J. McIntyre, D. Paul, S. T. Wilks, S. M. Ondreyco, S. Sedlacek, A. Melnyk, S. P. Oommen, Y. Wang, S. R. Peck and J. A. O’Shaughnessy (2019). “Evaluation of Miracle Mouthwash plus Hydrocortisone Versus Prednisolone Mouth Rinses as Prophylaxis for Everolimus-Associated Stomatitis: A Randomized Phase II Study.” Oncologist 24(9): 1153-1158.

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BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The objectives are to evaluate two steroid-based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus. MATERIALS AND METHODS: This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor-positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash [MMW] 480 mL recipe: 320 mL oral Benadryl [diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA], 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone [P] 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1-2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks. RESULTS: A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% (n = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse-related toxicity. CONCLUSION: Prophylactic use of steroid-containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse. IMPLICATIONS FOR PRACTICE: This prospective phase-II study showed that two steroid-containing mouthrinses substantially reduced incidences of all-grade and grade >/=2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose-delays and/or dose-reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost-effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor.

McCullough, P. A., H. S. Mehta, D. P. Cork, C. M. Barker, C. Gunnarsson, S. Mollenkopf, J. Van Houten and P. Verta (2019). “The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.” Journal of Medical Economics 22(9): 909-916.

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Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Guo, M. H. and A. R. Gregg (2019). “Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels.” Genetics in Medicine: Official Journal of the American College of Medical Genetics 21(9): 1940-1947.

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PURPOSE: Prenatal genetic carrier screening can identify parents at risk of having a child affected by a recessive condition. However, the conditions/genes most appropriate for screening remain a matter of debate. Estimates of carrier rates across genes are needed to guide construction of carrier screening panels. METHOD: We leveraged an exome sequencing database (n = 123,136) to estimate carrier rates across six major ancestries for 415 genes associated with severe recessive conditions. RESULTS: We found that 32.6% (East Asian) to 62.9% (Ashkenazi Jewish) of individuals are variant carriers in at least one of the 415 genes. For couples, screening all 415 genes would identify 0.17-2.52% of couples as being at risk for having a child affected by one of these conditions. Screening just the 40 genes with carrier rate >1.0% would identify more than 76% of these at-risk couples. An ancestry-specific panel designed to capture genes with carrier rates >1.0% would include 5 to 28 genes, while a comparable panethnic panel would include 40 genes. CONCLUSION: Our work guides the design of carrier screening panels and provides data to assist in counseling prospective parents. Our results highlight a high cumulative carrier rate across genes, underscoring the need for careful selection of genes for screening.

Al-Temimi, M. H., A. M. Dyurgerova, M. Kidon and S. Johna (2019). “Feeding Jejunostomy Tube Placed during Esophagectomy: Is There an Effect on Postoperative Outcomes?” Perm J Aug 26. [Epub ahead of print.].

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BACKGROUND: Feeding jejunostomy (FJ) tubes are routinely placed during esophagectomy. However, their effect on immediate postoperative outcomes in this patient population is not clear. OBJECTIVES: To evaluate the effect of FJ tube placement during esophagectomy on postoperative morbidity and mortality. METHODS: The National Surgical Quality Improvement Program database was used to evaluate the effect of FJ tube placement during esophagectomy on 30-day postoperative morbidity and mortality rates. A propensity score-matched cohort was used to compare postoperative outcomes of patients with and without FJ tubes. RESULTS: An FJ tube was placed in 45% of 2059 patients undergoing esophagectomy. The anastomotic leak rate was 13.5%. Patients with FJ tubes were more likely to have preoperative radiation therapy (59.6% vs 54.9%, p = 0.041), transhiatal esophagectomy (21.5% vs 19.2%, p = 0.012), a malignant diagnosis (93.2% vs 90.4%), and longer operative time (393 min vs 348 min, p < 0.001). In a case-matched cohort, mortality (2% vs 2.4%, p = 0.618) and severe morbidity (38.2% vs 34.6%, p = 0.128) were comparable between patients with and without FJ tubes. FJ tube placement was associated with higher overall morbidity (46% vs 38.6%, p = 0.002), superficial wound infection (6.3% vs 2.9%, p = 0.001), and return to the operating room (16.7% vs 12.5%, p = 0.016). In a subgroup of patients with anastomotic leak, FJ was associated with shorter hospital stay (20.1 days vs 24.3 days, p = 0.046). CONCLUSION: These mixed findings support selective rather than routine FJ tube placement during esophagectomy.

Kindratt, T., L. Callender, M. Cobbaert, J. Wondrack, F. Bandiera and D. Salvo (2019). “Health information technology use and influenza vaccine uptake among US adults.” Int J Med Inform 129: 37-42.

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OBJECTIVE: This study aims to estimate the association between health information technology (HIT) use and influenza vaccine uptake among US adults. MATERIALS AND METHODS: Data analysis was conducted using 2011-2015 National Health Interview Survey (NHIS) adult data (n = 169,912). HIT use was defined as having used computers (past 12 months) to seek health information, fill prescriptions, schedule appointments, communicate with health providers via email, and/or use online health chat groups. Crude and multivariable logistic regression models were used to estimate the odds of influenza vaccine uptake among HIT users versus non-users. Interactions were tested and stratified results were reported. RESULTS: Among US adults, 39.8% received an influenza vaccine in the past 12 months, while 48.6% reported any HIT use. After adjusting for covariates, any HIT users had 1.23 times greater odds (95% CI = 1.19, 1.27) of influenza vaccine uptake relative to non-HIT users. HIT use for looking up health information on the internet (OR = 1.19, 95% CI = 1.15, 1.23), filling prescriptions (OR = 1.56; 95% CI = 1.50, 1.66), scheduling appointments (OR = 1.56; 95% CI = 1.50, 1.66), and communicating with providers via email (OR = 1.51; 95% CI = 1.44, 1.59) were significantly associated with influenza vaccine uptake. DISCUSSION: HIT use is positively associated with influenza vaccine uptake. Each category of HIT use was independently associated with influenza vaccine uptake. To our knowledge, no other studies have evaluated the relationship between HIT use and influenza vaccine uptake. Our results are exploratory and represent an association, not a causal relationship. Longitudinal, confirmatory studies are also needed to verify our cross-sectional findings.