Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). METHODS: Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3-93.2%). The median DoR was 19.3 (95% CI: 15.8-25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8-24.8) months and 22.0 (95% CI: 16.8-26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. CONCLUSIONS: Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03386955.

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC. METHODS: Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). RESULTS: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported. CONCLUSIONS: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.

A comparison of patient appraisal of professional skills for GPs in training participating in differing education programs.

BACKGROUND: Medical boards and healthcare providers internationally are coming under increasing pressure to attract international medical graduates (IMGs) and overseas trained doctors (OTDs) to cope with predicted general practice (GP) doctor shortages. Various pathways to registration are made available for this purpose. There is very little understanding of the effects of different training pathways to licensing and registration on the ability of IMGs and OTDs, as well as locally trained doctors, to acquire the desirable professional skills deemed necessary for working effectively in the primary care sector. METHODS: Feedback from patients was collected at the end of their scheduled consultation with their doctor using a questionnaire consisting of 13 Likert scale items that asked them to rate their experience of the consultation. Feedback was obtained for doctors going through the Royal Australian College of General Practice (RACGP) Practice Experience Program (PEP) and the Australian General Practice Training Program (AGPT), with the former intended primarily for IMGs and OTDs, and the latter for local medical graduates including from New Zealand. Patient feedback was also obtained for patients visiting already Fellowed and experienced GPs for comparative purposes, resulting in data for three groups of doctors (two trainee, one already Fellowed). Rater consistency and agreement measures, analysis of variance, principal component analysis, t-tests and psychometric network analysis were undertaken between and within groups to identify similarities and differences in patient experience and professionalism of doctors. RESULTS: There was a small but significant difference in average patient raw scores given to PEP and AGPT doctors (90.25, 90.97%), with the highest scores for 'Respect shown' (92.24, 93.15%) and the lowest for 'Reassurance' 89.38, 89.84%). Male patients gave lower scores (89.56%) than female patients (91.23%) for both groups of doctors. In comparison, patients gave experienced GPs an average 91.38% score, with male patients giving a lower average score than female patients (90.62, 91.93%). Two components were found in the patient data (interpersonal communication, caring/empathy) that account for over 80% of the variance. When patient scores were aggregated by doctor, the average PEP and AGPT doctor scores received were 90.27 and 90.99%, in comparison to the average experienced GP score of 91.43%. Network analysis revealed differences in the connectedness of items between these two groups as well as in comparison with experienced GPs, suggesting that PEP doctors' skills are less cohesively developed in the areas of listening ability, explaining and providing reassurance. CONCLUSIONS: The small but statistically significant differences between doctor groups reported in this preliminary study are supplemented by percentile analysis, network analysis and principal component analysis to identify areas for further exploration and study. There is scope for improving the integration of interpersonal communication skills of GPs in Training with their caring and empathy skills, when compared with experienced GPs as a benchmark. Suggestions are made for enhancing professional skills from a patients' perspective in future training programs.

Are there differences between SIMG surgeons and locally trained surgeons in Australia and New Zealand, as rated by colleagues and themselves?

BACKGROUND: Representation of specialist international medical graduates (SIMGs) in specific specialties such as surgery can be expected to grow as doctor shortages are predicted in the context of additional care provision for aging populations and limited local supply. Many national medical boards and colleges provide pathways for medical registration and fellowship of SIMGs that may include examinations and short-term training. There is currently very little understanding of how SIMGs are perceived by colleagues and whether their performance is perceived to be comparable to locally trained medical specialists. It is also not known how SIMGs perceive their own capabilities in comparison to local specialists. The aim of this study is to explore the relationships between colleague feedback and self-evaluation in the specialist area of surgery to identify possible methods for enhancing registration and follow-up training within the jurisdiction of Australia and New Zealand. METHODS: Feedback from 1728 colleagues to 96 SIMG surgeons and 406 colleagues to 25 locally trained Fellow surgeons was collected, resulting in 2134 responses to 121 surgeons in total. Additionally, 98 SIMGs and 25 Fellows provided self-evaluation scores (123 in total). Questionnaire and data reliability were calculated before analysis of variance, principal component analysis and network analysis were performed to identify differences between colleague evaluations and self-evaluations by surgeon type. RESULTS: Colleagues rated SIMGs and Fellows in the 'very good' to 'excellent' range. Fellows received a small but statistically significant higher average score than SIMGs, especially in areas dealing with medical skills and expertise. However, SIMGs received higher scores where there was motivation to demonstrate working well with colleagues. Colleagues rated SIMGs using one dimension and Fellows using three, which can be identified as clinical management skills, inter-personal communication skills and self-management skills. On self-evaluation, both SIMGs and Fellows gave themselves a significant lower average score than their colleagues, with SIMGs giving themselves a statistically significant higher score than Fellows. CONCLUSIONS: Colleagues rate SIMGs and Fellows highly. The results of this study indicate that SIMGs tend to self-assess more highly, but according to colleagues do not display the same level of differentiation between clinical management, inter-personal and self-management skills. Further research is required to confirm these provisional findings and possible reasons for lack of differentiation if this exists. Depending on the outcome, possible support mechanisms can be explored that may lead to increased comparable performance with locally trained graduates of Australia and New Zealand in these three dimensions.

Activating people to partner in health and self-care: use of the Patient Activation Measure.

Patient activation is a behavioural concept and is at the heart of personalised care. It is defined as an individual's knowledge, skill and confidence for managing their health and health care. Evidence indicates that patient activation scores can predict health behaviour and are closely linked to various clinical outcomes: reduced unnecessary emergency department visits, hospital admissions and re-admissions. Patients with lower activation levels (25-40% of the population) are less likely to adopt healthy behaviour, and more likely to have poorer clinical outcomes and higher rates of hospitalisation. Effective interventions can improve a patient's activation level, and positive change in activation equates to positive change in self-care behaviour. But to improve patient activation, we must first measure it using a robust evidence-based tool such as the Patient Activation Measure (PAM) survey. Armed with the patient's PAM score, providers can tailor their care and help patients achieve better self-care, which can improve outcomes of care and reduce unnecessary health care utilisation. The PAM is also useful for population segmentation and risk stratification - to target interventions and health strategies to meet the needs of patients who are at different points along the activation continuum, to measure the performance of health care systems, and to evaluate the effectiveness of health care interventions. The role of patient activation requires further serious consideration if we are to improve the long-term health and wellbeing of all Australians. The PAM tool is a feasible and cost-effective solution for achieving the Quadruple Aim - improving population health, the cost-efficiency of the health system, and patient and provider experience.

Colleague appraisal of Australian general practitioners in training: an analysis of multisource feedback data.

BACKGROUND: Multisource feedback is an evidence-based and validated tool used to provide clinicians, including those in training, feedback on their professional and interpersonal skills. Multisource feedback is mandatory for participants in the Royal Australian College of General Practitioners Practice Experience Program and for some Australian General Practice Training Registrars. Given the recency of the Practice Experience Program, there are currently no benchmarks available for comparison within the program and to other comparable cohorts including doctors in the Australian General Practice Training program. The aim of this study is to evaluate and compare colleague feedback within and across General Practice trainee cohorts. METHODS: Colleague feedback, from multisource feedback of Practice Experience Program participants and Australian General Practice Training Registrars, collected between January 2018 and April 2020, was compared to identify similarities and differences. Analyses entailed descriptive statistics, between and within groups rater consistency and agreement measures, principal component analysis, t-tests, analysis of variance, and psychometric network analysis. RESULTS: Colleague ratings of Practice Experience Program participants (overall average 88.58%) were lower than for Registrars (89.08%), although this difference was not significant. 'Communication with patients' was rated significantly lower for Practice Experience Program participants (2.13%) while this group was rated significantly better for their 'Ability to say no' (1.78%). Psychometric network analyses showed stronger linkages between items making up the behavioural component (compared to the items of the performance and self-management components, as found by principal component analysis) for Practice Experience Program participants as compared to Registrars. Practice Experience Program participants were stronger in clinical knowledge and skills as well as confidentiality, while Registrars were stronger in communicating with patients, managing their own stress, and in their management and leadership skills. CONCLUSIONS: The multisource feedback scores of doctors undertaking the Practice Experience Program suggests that, while all mean values are 'very good' to 'excellent', there are areas for improvement. The linkages between skills suggests that Practice Experience Program doctors' skills are somewhat isolated and have yet to fully synthesise. We now have a better understanding of how different groups of General Practitioners in training compare with respect to professional and interpersonal skills. Based on the demonstrated differences, the Practice Experience Program might benefit from the addition of educational activities to target the less developed skills.

Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor selective for EGFR-sensitizing and T790M mutations. This study was designed to evaluate the safety, efficacy, and pharmacokinetics of rezivertinib for patients having advanced NSCLC with EGFR T790M mutation. METHODS: This phase 1 study (NCT03386955) was conducted across 20 sites in the People's Republic of China. Patients received rezivertinib at six oral dose levels (30 mg, 60 mg, 120 mg, 180 mg, 240 mg, 300 mg) once daily until disease progression, unacceptable toxicity, or patient withdrawal. The primary end points were safety for the dose-escalation phase and objective response rate by the blinded independent central review for the total study population. RESULTS: A total of 19 patients in dose-escalation phase using the standard 3 + 3 design principle and 153 patients in dose-expansion phase were enrolled from September 11, 2017, to August 23, 2019. The data cutoff date was on June 15, 2020. No dose-limiting toxicity occurred in the dose-escalation phase. The treatment-related adverse events were observed in 82.0% (141 of 172) of patients, and 17.4% (30 of 172) had grade greater than or equal to 3, among which decreased neutrophil count (2.9%), leukopenia (2.9%), and pneumonia (2.9%) were the most common. The overall blinded independent central review-evaluated objective response rate was 59.3% (102 of 172, 95% confidence interval: 51.6-66.7), and the median progression-free survival was 9.7 (95% confidence interval: 8.3-11.1) months. CONCLUSIONS: Rezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.

120 mJ, 1 kHz, picosecond laser at 515 nm.

We report on a 1 kHz, 515 nm laser system, based on a commercially available 230 W average power Yb:YAG thin-disk regenerative amplifier, developed for pumping one of the last optical parametric chirped pulse amplification (OPCPA) stages of the Allegra laser system at ELI Beamlines. To avoid problems with self-focusing of picosecond pulses, the 1030 nm output pulses are compressed and frequency doubled with an LBO crystal in vacuum. Additionally, development of a thermal management system was needed to ensure stable phase matching conditions at high average power. The resulting 515 nm pulses have an energy of more than 120 mJ with SHG efficiency of 60% and an average RMS stability of 1.1% for more than 8 h.

Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC.

Single-agent osimertinib is the standard of care for the first-line treatment of advancedEGFR+ NSCLC and remained the only marketed third-generation EGFR tyrosine kinase inhibitor (TKI) until March 2020 when almonertinib (HS-10296) was approved in the People's Republic of China for the treatment of advanced EGFR T790M+ NSCLC based on a phase 2 expansion study of a phase 1/2 trial. In this review, we profiled many of the third-generation EGFR TKIs in late-stage clinical development (e.g., almonertinib, lazertinib, alflutinib1, rezivertinib, ASK120069, SH-1028, D-0316, and abivertinib) based on their interim results from phase 1 and phase 2 trials, and included the designs of the phase 3 trials and their chemical structures when publicly available. We also listed other third-generation EGFR TKIs in pipeline development based on the search of clinical trial registration websites. In addition, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, mavelertinib), including phase 3 results of rociletinib and naquotinib. We further profiled combination clinical trial design of the third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704), and ACROSS2 (NCT04500717) that if positive can potentially usher in the next standard of care for advanced EGFR+ NSCLC.

Discovery of PEGylated 6-Benzhydryl-4-amino-quinazolines as Peripherally Restricted CB1R Inverse Agonists.

The 6-benzhydryl-4-amino-quinolin-2-ones are peripherally restricted CB1 receptor inverse agonists (CB1RIAs) that have been reported to attenuate obesity and improve insulin sensitivity in the diet-induced obese (DIO) mouse model. However, chronic dosing of select compounds from the series showed time-dependent brain accumulation despite a low brain/plasma exposure ratio. To address this issue, a PEGylation approach was employed to identify a novel series of homodimeric 6-benzhydryl-4-amino-quinazoline-PEG conjugates with an extended half-life. The lead compound 18 engaged peripheral CB1Rs in a gastrointestinal (GI) tract motility study and demonstrated a high level of peripheral restriction in a chronic DIO mouse pharmacokinetic study.

Correction to: Multisource feedback as part of the medical board of Australia's professional performance framework: outcomes from a preliminary study.

Following publication of the original article [1], the author reported that Fig. 4 was missing. This has now been corrected in the original article.

Multisource feedback as part of the Medical Board of Australia's Professional Performance Framework: outcomes from a preliminary study.

BACKGROUND: The recent introduction of the Professional Performance Framework by the Medical Board of Australia is intended to strengthen continuing professional development for the 100,000 or so medical practitioners in Australia. An important option within the Framework is the use of multisource feedback from patients, colleagues and self-evaluations to allow doctors to reflect on their performance and identify methods for self-improvement. The aim of this study is to explore the relationships between patient feedback, colleague feedback, and self-evaluation using the same questionnaires as used by patients and colleagues. METHODS: Feedback data for around 2000 doctors belonging to four different groups were collected through non-probability sampling from nearly 100,000 patients and 24,000 colleagues. Reliability analysis was performed using single measures intraclass coefficients, Cronbach' alpha and signal-to-noise ratios. Analysis of variance was used to identify significant differences in scores between items and sub-populations of doctors; principal component analysis involving Kaiser-Meyer-Olkin (KMO) sampling adequacy and Bartlett's test for sphericity was used to reveal components of doctor performance; and correlation analysis was used for identifying convergence between sets of scores from different sources. RESULTS: Patients rated doctors highest on respect shown and lowest on reassurance provided. Colleagues rated doctors highest on trustworthiness and lowest on ability to say 'no'. With regard to self-evaluation, doctors gave themselves lower scores on the patient questionnaire and the colleague questionnaire (10 and 12%, respectively) than they received from their patients and colleagues. There were weak but positive correlations between self-scores and scores received indicating some convergence of agreement, with doctors feeling more comfortable with self-evaluation from the perspective of patients than from colleagues. CONCLUSIONS: Supplementing patient and colleague feedback with self-evaluation may help doctors confirm for themselves areas for enhanced CPD through convergence. If self-evaluation is used, the colleague questionnaire may be sufficient, since aspects of clinical competence, management, communication and leadership as well as patient care can be addressed through colleague items. Mentoring of doctors in CPD should aim to make doctors feel more comfortable about being rated by colleagues to enhance convergence between self-scores and evaluations from the perspective of colleagues.

6-Benzhydryl-4-amino-quinolin-2-ones as Potent Cannabinoid Type 1 (CB1) Receptor Inverse Agonists and Chemical Modifications for Peripheral Selectivity.

A novel series of 6-benzhydryl-4-amino-quinolin-2-ones was discovered as cannabinoid type 1 receptor (CB1R) inverse agonists based on the high-throughput screening hit, compound 1a. Structure-activity relationships were studied to improve in vitro/in vivo pharmacology and restrict distribution to the peripheral circulation. We adopted several strategies such as increasing topological polar surface area, incorporating discrete polyethylene glycol side chains, and targeting P-glycoprotein (P-gp) to minimize access to the brain. Compound 6a is a P-gp substrate and a potent and highly selective CB1R inverse agonist, demonstrating excellent in vivo metabolic stability and a low brain to plasma ratio. However, brain receptor occupancy studies showed that compound 6a may accumulate in brain with repeat dosing. This was evidenced by compound 6a inhibiting food intake and inducing weight loss in diet-induced obese mice. Thus, a strategy based on P-gp efflux may not be adequate for peripheral restriction of the disclosed quinolinone series.

Patient Experience of Australian General Practices.

The number of data-based research articles focusing on patient sociodemographic profiling and experience with healthcare practices is still relatively small. One of the reasons for this relative lack of research is that categorizing patients into different demographic groups can lead to significant reductions in sample numbers for homogeneous subgroups. The aim of this article is to identify problems and issues when dealing with big data that contains information at two levels: patient experience of their general practice, and scores received by practices. The Practice Accreditation and Improvement Survey (PAIS) consisting of 27 five-point Likert items and 11 sociodemographic questions is a Royal Australian College of General Practitioners (RACGP)-endorsed instrument for seeking patient views as part of the accreditation of Australian general practices. The data were collected during the 3-year period May 2011-July 2014, during which time PAIS was completed for 3734 individual general practices throughout Australia involving 312,334 anonymous patients. This represents over 60% of practices in Australia, and ∼75% of practices that undergo voluntary accreditation. The sampling method for each general practice was convenience sampling. The results of our analysis show how sociodemographic profiles of Australian patients can affect their ratings of practices and also how the location of the practice (State/Territory, remote access area) can affect patient experience. These preliminary findings can act as an initial set of results against which future studies in patient experience trends can be developed and measured in Australia. Also, the methods used in this article provide a methodological framework for future patient experience researchers to use when dealing with data that contain information at two levels, such as the patient and practice. Finally, the outcomes demonstrate that different subgroups can experience healthcare provision differently, especially indigenous patients and young patients. The implications of these findings for healthcare policy and priorities will need to be further investigated.

Nonlinear dynamics of double-pass cross-polarized wave generation in the saturation regime.

The conversion efficiency of cross-polarized wave (XPW) generation can be improved using two separate thinner nonlinear crystals versus a single thick one, due to the evolution of the beam sizes and individual phases after the first crystal. In this paper, we present an alternative scheme in which a curved mirror is used to reimage a plane just after the BaF2 crystal for a second pass. We also develop a simple analytic model for XPW conversion that describes the origin of a nonlinear phase mismatch and nonlinear lensing for both the fundamental wave and XPW. Coupled with the numerical solution for the process and the Fresnel propagation after the first pass, we also explore the factors that affect the efficiency of saturated, seeded XPW conversion. These include the development of the on-axis relative phase difference in the first crystal and after it (during free-space propagation), mode matching, wavefront curvature difference, and crystal tuning angle. We also experimentally demonstrate that the beam quality of the XPW signal after the second pass can be improved by the reimaging.

Spatial-spectral characterization of focused spatially chirped broadband laser beams.

Proper alignment is critical to obtain the desired performance from focused spatially chirped beams, for example in simultaneous spatial and temporal focusing (SSTF). We present a simple technique for inspecting the beam paths and focusing conditions for the spectral components of a broadband beam. We spectrally resolve the light transmitted past a knife edge as it was scanned across the beam at several axial positions. The measurement yields information about spot size, M2, and the propagation paths of different frequency components. We also present calculations to illustrate the effects of defocus aberration on SSTF beams.

An initiative to improve adherence to evidence-based guidelines in the treatment of URIs, sinusitis, and pharyngitis.

BACKGROUND: Upper respiratory infections, acute sinus infections, and sore throats are common symptoms that cause patients to seek medical care. Despite well-established treatment guidelines, studies indicate that antibiotics are prescribed far more frequently than appropriate, raising a multitude of clinical issues. METHODS: The primary goal of this study was to increase guideline adherence rates for acute sinusitis, pharyngitis, and upper respiratory tract infections (URIs). This study was the first Plan-Do-Study-Act (PDSA) cycle in a quality improvement program at an internal medicine resident faculty practice at a university-affiliated community hospital internal medicine residency program. To improve guideline adherence for respiratory infections, a package of small-scale interventions was implemented aimed at improving patient and provider education regarding viral and bacterial infections and the necessity for antibiotics. The data from this study was compared with a previously published study in this practice, which evaluated the adherence rates for the treatment guidelines before the changes, to determine effectiveness of the modifications. After the first PDSA cycle, providers were surveyed to determine barriers to adherence to antibiotic prescribing guidelines. RESULTS: After the interventions, antibiotic guideline adherence for URI improved from a rate of 79.28 to 88.58% with a p-value of 0.004. The increase of adherence rates for sinusitis and pharyngitis were 41.7-57.58% (p=0.086) and 24.0-25.0% (p=0.918), respectively. The overall change in guideline adherence for the three conditions increased from 57.2 to 78.6% with the implementations (p<0.001). In planning for future PDSA cycles, a fishbone diagram was constructed in order to identify all perceived facets of the problem of non-adherence to the treatment guidelines for URIs, sinusitis, and pharyngitis. From the fishbone diagram and the provider survey, several potential directions for future work are discussed. CONCLUSIONS: Passive interventions can result in small changes in antibiotic guideline adherence, but further PDSA cycles using more active methodologies are needed.

Simultaneous spatial and temporal focusing for tissue ablation.

Simultaneous spatial temporal focusing (SSTF) is used to deliver microjoule femtosecond pulses with low numerical aperture geometries (<0.05 NA) with characteristics that are significantly improved compared to standard focusing paradigms. Nonlinear effects that would normally result in focal plane shifts and focal spot distortion are mitigated when SSTF is employed. As a result, it is shown that SSTF will enable surgical implementations that are presently inhibited.