Infant Social Attention Associated with Elevated Likelihood for Autism Spectrum Disorder: A Multi-Method Comparison.

PURPOSE: The study aimed to compare eye tracking (ET) and manual coding (MC) measures of attention to social and nonsocial information in infants with elevated familial likelihood (EL) of autism spectrum disorder (ASD) and low likelihood of ASD (LL). ET provides a temporally and spatially sensitive tool for measuring gaze allocation. Existing evidence suggests that ET is a promising tool for detecting distinct social attention patterns that may serve as a biomarker for ASD. However, ET is prone to data loss, especially in young EL infants. METHODS: To increase evidence for ET as a viable tool for capturing atypical social attention in EL infants, the current prospective, longitudinal study obtained ET and MC measures of social and nonsocial attention in 25 EL and 47 LL infants at several time points between 3 and 24 months of age. RESULTS: ET data was obtained with a satisfactory success rate of 95.83%, albeit with a higher degree of data loss compared to MC. Infant age and ASD likelihood status did not impact the extent of ET or MC data loss. There was a significant positive association between the ET and MC measures of attention, and separate analyses of attention using ET and AC measures yielded comparable findings. These analyses indicated group differences (EL vs. LL) in age-related change in attention to social vs. nonsocial information. CONCLUSION: Together, the findings support infant ET as a promising approach for identifying very early markers associated with ASD likelihood.

Safety and Efficacy of Low-Dose Versus High-Dose Parenteral Ketorolac for Acute Pain Relief in Patients 65 Years and Older in the Emergency Department.

Background There is limited data surrounding acute pain management in elderly ED patients. Ketorolac is a potent non-steroidal anti-inflammatory drug (NSAID) with dose/duration-dependent side effects. There is evidence that an analgesic ceiling effect exists for parenteral ketorolac doses greater than 10 milligrams (mg); however, this has not been studied in patients 65 years and older. Methods This was a retrospective chart review of ED patients 65 years and older who received at least one dose of parenteral ketorolac. Patients were separated into two cohorts based on the ketorolac dose received: 15 mg IV or 30 mg intramuscular (IM) and 30 mg IV or 60 mg IM. The primary objective was to evaluate the analgesic efficacy of parenteral ketorolac doses measured as needing rescue analgesia from 30 minutes to 2 hours after ketorolac administration. Secondary objectives included changes in pain scores and the occurrence of adverse drug events commonly associated with ketorolac. Results Two-hundred and sixty patients received ketorolac doses of 15 mg IV or 30 mg IM, and 52 received 30 mg IV or 60 mg IM. The primary outcome occurred in seven of 52 patients who received ketorolac 30 mg IV or 60 mg IM and 17 of 260 patients who received ketorolac 15 mg IV or 30 mg IM (13.5% vs. 6.5%, p=0094; OR: 2.22, 95% CI: 0.87-5.67). The average change in pain scores were 2.9 (±3.1) and 2.8 (±2.9) for patients who received doses 30 mg IV or 60 mg IM compared to doses 15 mg IV or 30 mg IM, respectively (p=0.154). The occurrence of adverse events was low in both groups. Conclusion Parenteral ketorolac doses of 15 mg IV or 30 mg IM did not demonstrate a greater need for rescue analgesia compared to doses of 30 mg IV or 60 mg IM.

A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA-mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2- advanced (locally unresectable) or metastatic disease (HR+/HER2- mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2- mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2- mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2- mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.

A Systematic Literature Review of the Prognostic and Predictive Value of PIK3CA Mutations in HR+/HER2- Metastatic Breast Cancer.

PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, representing an important potential target for systemic therapy. Prognostic and predictive values associated with PIK3CA mutations are not well understood. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and conference abstracts was performed for English-language articles published January 1993 through April 2019. Articles were categorized by treatment arms based on experimental and treatment drug classes. Information on progression-free survival (PFS), hazard ratios, overall survival, response rate, and clinical benefit rate was obtained. A total of 17 studies were included. Among those evaluating non-PI3Ki based therapies, 91% showed numerically shorter median PFS, ranging from 1.5 to 19.2 months and 1.8 to 29.6 months for the mutant versus non-mutant subgroups, respectively. Where reported (n = 13 studies), PFS was shorter between those arms offering endocrine monotherapy (range, 1.6-14.7 months) compared with a corresponding targeted therapy + endocrine monotherapy (range, 3.9-29.6 months). Of 5 PI3Ki-based arms comparing PFS, higher median PFS in PIK3CA mutant versus non-mutant cases was demonstrated. PFS was shorter for patients with PIK3CA mutant (range, 1.6-19.2 months) compared with PIK3CA wild-type (range, 1.8-29.6 months) in 10 (71%) of 14 treatment arms reporting PFS. Studies (n = 4) not reporting PFS reported response rate, but there were no clear directional trends. The presence of PIK3CA mutations may be associated with worse clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Clinical outcomes such as PFS may be improved using a combination of PI3Ki-based therapies and endocrine therapies among this population. However, more research is warranted to fully elucidate this association.

Systematic literature review of clinical trials of endocrine therapies for premenopausal women with metastatic HR+ HER2- breast cancer.

Several endocrine-based therapies have recently been evaluated as treatments for premenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC). We conducted a systematic review and assessed the feasibility of an indirect treatment comparison (ITC) to characterize the comparative efficacy of endocrine-based therapies in this setting. A systematic literature review (SLR) of Medline, EMBASE, Cochrane Library and key conferences was performed to identify randomized clinical trials (RCTs) satisfying the following criteria: (a) included pre/perimenopausal women with HR+/HER2- mBC, (b) included endocrine-based therapies, (c) reported efficacy, safety, or quality of life outcomes, and (d) was published in 2007 or later (when HER2 testing was standardized). The clinical and methodological similarities across trials were assessed to evaluate the feasibility of an ITC. Four RCTs (PALOMA-3, MONARCH-2, KCSG BR10-04 and MONALEESA-7) and eight regimens (palbociclib + fulvestrant + goserelin, fulvestrant + goserelin, abemaciclib + fulvestrant + gonadotropin-releasing hormone agonist [GnRHa], fulvestrant + GnRHa, anastrozole + goserelin, goserelin, ribociclib + NSAI/tamoxifen + goserelin and NSAI/tamoxifen + goserelin) were selected. MONALEESA-7 was the only phase 3 trial investigating endocrine-based therapies as first-line in only pre/perimenopausal women with HR+/HER2- mBC; the other three trials focused on the ET-failure setting and their pre/perimenopausal populations were relatively small. ITCs were methodologically unfeasible due to critical differences in treatment settings and lack of common comparators across trials. Therefore, we were not able to characterize the relative efficacy of the different endocrine-based therapies available in the premenopausal HR+/HER2- mBC setting. This systematic review provides a comprehensive assessment of the available trial evidence on the efficacy and safety of endocrine-based therapies for premenopausal women with HR+/HER2- mBC. Only four trials have reported relevant data in this setting, and MONALEESA-7 is currently the only trial focused on premenopausal HR+ HER2- mBC in the first-line setting.