Unusual Adverse Events in a Patient With BRAF-Mutated Non-Small Cell Lung Cancer Treated With BRAF/MEK Inhibition.

BRAF/MEK inhibition remains standard of care for treatment of BRAF-mutated non-small cell lung cancer (NSCLC). Although common adverse events (AEs) have been reported through clinical trials and ongoing clinical practice, only a handful of reports have detailed unusual adverse events associated with these medications. This report presents a patient with BRAF-mutated NSCLC treated with dabrafenib and trametinib who experienced 2 unusual AEs-Sweet syndrome and MEK-associated retinopathy-that responded to steroid treatment. The patient was able to continue BRAF/MEK inhibition through a coordinated multidisciplinary approach. This case highlights the importance for all clinicians to recognize unusual AEs associated with BRAF/MEK inhibition, particularly in the setting of expanded use for all BRAF V600E-mutated solid tumors.

Design Parameters for Planning the Sample Size of Individual-Level Randomized Controlled Trials in Community Colleges.

The last two decades have seen a dramatic increase in randomized controlled trials (RCTs) conducted in community colleges. Yet, there is limited empirical information on the design parameters necessary to plan the sample size for RCTs in this context. For a blocked student-level random assignment research design, key design parameters for the minimum detectable true effect (MDTE) are the within-block outcome standard deviation (σ|S) and the within-block outcome variance explained by baseline covariates like student characteristics (R|S2). We provide empirical estimates of these key design parameters, discussing the pattern of estimates across outcomes (enrollment, credits earned, credential attainment, and grade point average), semesters, and studies. The main analyses use student-level data from 8 to 14 RCTs including 5,649-7,099 students (depending on the outcome) with follow-up data for 3 years. The following patterns are observed: the within-block standard deviation (σ|S) and therefore the MDTE can be much larger in later semesters for enrollment outcomes and cumulative credits earned; there is substantial variation across studies in σ|S for degree attainment; and baseline covariates explain less than 10% of the variation in student outcomes. These findings indicate that when planning the sample size for a study, researchers should be mindful of the follow-up period, use a range of values to calculate the MDTE for outcomes that vary across studies, and assume a value of R|S2 between 0 and 0.05. A public database created for this paper includes parameter estimates for additional RCTs and students.

The Impact of Telephonic Follow-Up Within 2 Business Days Postdischarge on 30-Day Readmissions for Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is a chronic condition associated with high rates of hospital readmissions. The prevalence and costs of HF are expected to rise dramatically by 2030 (Heidenreich,et al., 2013). OBJECTIVE: A 24-month, retrospective study was conducted using electronic medical record (EMR) chart review, seeking to identify if postdischarge follow-up phone calls decreased 30-day readmissions in individuals with HF. METHODS: The study included 705 adult participants who were admitted to the hospital for HF. Some received a postdischarge call within 2 business days of discharge, and some did not. RESULTS: Participants who received the postdischarge call were less likely to be readmitted (20.1%) than participants who did not receive a postdischarge call (28.8%; p = .007). Participants who received the postdischarge call were more likely to have a follow-up visit within 14 days (70.1%) than participants who did not receive a postdischarge call (30.2%; p < .001). CONCLUSIONS: The findings from this study may help to drive future transitional care strategies for individuals diagnosed with HF. IMPLICATIONS FOR NURSING: Nurse-led transitional care interventions offer potential solutions to ensure safe, effective hospital discharges.

Demographic determinants and effect of pre-operative angiotensin converting enzyme inhibitors and angiotensin receptor blockers on the occurrence of atrial fibrillation after CABG surgery.

BACKGROUND: Atrial fibrillation (AF) occurs in about 27% to 40% of post cardiac surgery patients. AF following coronary artery bypass graft surgery (CABG) is associated with a two-fold increase in morbidity and mortality. Various demographic risk factors and medications have been studied to predict the occurrence of this arrhythmia. The role of angiotensin related medications on the occurrence of AF in CABG patients is not determined. METHODS: Retrospective clinical and statistical analysis was made of all the patients who had undergone CABG surgery at Lehigh Valley Hospital during the years 2005 and 2006. Patients with chronic AF and those undergoing valvular surgery with CABG were excluded. Statistic analysis included chi-square test for categorical and student t-test for continuous variables. RESULTS: 757 patients (560 males and 197 females) were studied. AF occurred in 19% of the patients. Age (70.5 vs. 65.1, p < 0.005. OR per year of age: 1.02, 95%CI: 1.018-1.023) and presence of hypertension (OR: 1.92, 95%CI: 1.086-3.140, p = 0.025) were significantly associated with occurrence of AF. Neither ARBs (OR: 0.78, 95%CI: 0.431-1.410, p = 0.41) nor ACE inhibitors (OR: 1.01, 95%CI: 0.753-1.608, p = 0.63) reduced the occurrence of post operative AF. Patients with post operative AF had a significantly longer hospital stay (9.5 +/- 5.4 days vs. 6.9 +/- 4.3 days, p = 0.001). CONCLUSIONS: Advanced age and presence of hypertension were independent predictors of post-CABG AF. Patients with post operative AF had significantly longer hospital stay. Neither ARBs nor ACE inhibitors were associated with reduction of post-surgical AF. Further studies are needed to better delineate the role of angiotensin related medications on reduction of post-surgical AF.

Retinal pigment epithelial detachment in sarcoidosis.

PURPOSE: To report primary retinal pigment epithelial (RPE) detachments in sarcoidosis. DESIGN: Case report. METHODS: Clinical findings, fluorescence angiography and optical coherence tomography (OCT) results are presented and discussed. RESULTS: A 54-year-old Hispanic male with biopsy proved sarcoidosis presented with multiple RPE detachment in both eyes. Except for acute iritis, there were no other ocular manifestations of sarcoidosis. CONCLUSIONS: Detachments of the RPE may be a rare manifestation of ocular sarcoidosis.

Prospective Evaluation of Fractional CO2 Laser Treatment of Mature Burn Scars.

The authors conducted a prospective study of fractional CO2 laser treatment of mature burn scars, comparing objective and subjective scar measurements evaluating at least one treatment and one control scar on the same patient pre- and post treatments. After institutional review board approval, burn survivors with mature blatant burn scars were invited to enter the study. A series of three fractional CO2 laser treatments was performed in an office setting, using topical anesthetic cream, at 40 to 90 mJ, 100 to 150 spots per cm(2). Subjective and objective measurements of scar physiology and appearance were performed before and at least 1 month after the treatment series on both the treated and the control scar. A total of 80 scars, 48 treatment and 32 control scars, were included in the study. Treatment pain score averaged at 4.7/10 during and at 2.4/10 5 minutes after the treatment. All treated scars showed improvement. Objectively measured thickness, sensation, erythema, and pigmentation improved significantly in the treated scars (P = .001, .001, .004, and .001). Elasticity improved, but without statistical significance. Vancouver scar scale assessments by an independent observer improved from 8 to 6; patient self-reported pain and pruritus remained unchanged in both groups. Fractional CO2 laser treatment is a promising entity in the treatment of burn scars. Our study results show significant differences in objective measurements between the treated scars and the untreated control scars over the same time period. In scar treatment studies, the patient/observer and Vancouver scar scales may not be sensitive enough to detect outcome differences.

Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer.

INTRODUCTION: The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. METHODS: From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. RESULTS: All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. CONCLUSION: Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients' outcomes.

Clinical characteristics and treatment-related biomarkers associated with response to high-dose interleukin-2 in metastatic melanoma and renal cell carcinoma: retrospective analysis of an academic community hospital's experience.

BACKGROUND: Immunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital. PATIENTS/METHODS: We retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 - 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves. RESULTS: Variables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p < 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred. CONCLUSIONS: High-dose IL-2 can be safely administered by an experienced team in a non-intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient's baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy.

Individualized Risk of Surgical Complications: An Application of the Breast Reconstruction Risk Assessment Score.

BACKGROUND: Risk discussion is a central tenet of the dialogue between surgeon and patient. Risk calculators have recently offered a new way to integrate evidence-based practice into the discussion of individualized patient risk and expectation management. Focusing on the comprehensive Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database, we endeavored to add plastic surgical outcomes to the previously developed Breast Reconstruction Risk Assessment (BRA) score. METHODS: The TOPS database from 2008 to 2011 was queried for patients undergoing breast reconstruction. Regression models were constructed for the following complications: seroma, dehiscence, surgical site infection (SSI), explantation, flap failure, reoperation, and overall complications. RESULTS: Of 11,992 cases, 4439 met inclusion criteria. Overall complication rate was 15.9%, with rates of 3.4% for seroma, 4.0% for SSI, 6.1% for dehiscence, 3.7% for explantation, 7.0% for flap loss, and 6.4% for reoperation. Individualized risk models were developed with acceptable goodness of fit, accuracy, and internal validity. Distribution of overall complication risk was broad and asymmetric, meaning that the average risk was often a poor estimate of the risk for any given patient. These models were added to the previously developed open-access version of the risk calculator, available at http://www.BRAscore.org. CONCLUSIONS: Population-based measures of risk may not accurately reflect risk for many individual patients. In this era of increasing emphasis on evidence-based medicine, we have developed a breast reconstruction risk assessment calculator from the robust TOPS database. The BRA Score tool can aid in individualizing-and quantifying-risk to better inform surgical decision making and better manage patient expectations.

Millet preference, effects of planting date on infestation, and adult and larval use of proso millet by Ostrinia nubilalis (Lepidoptera: Crambidae).

The interaction between millet and European corn borer, Ostrinia nubilalis (Hübner), was investigated to gain insight into whether millet could serve as a refuge or trap crop for O. nubilalis management. In 1995, 1996, and 1999, millet selection studies were conducted in North Dakota and New York with four millet species. Proso millet, Panicum milliaceum L., had the highest infestation and widest distribution of O. nubilalis developmental stages, indicating the presence of both univoltine and bivoltine ecotypes. Siberian foxtail millet, Setaria italica (L.) Beauvois, harbored the greatest number of adults, followed by German foxtail millet, Setaria italica (L.) Beauvois. These two millets appeared to serve as better aggregation sites than proso millet. In North Dakota in 1997, proso millet planting date studies showed later planting dates were more heavily infested than earlier dates; in 1998, this trend was reversed. The change in trends between years was probably a result of differences in the respective growing seasons and subsequent differences in O. nubilalis flights. Adult sampling showed that both old and young females aggregated in proso millet during the day; however, at night, it appeared that young females moved out of millet to oviposit, whereas old females remained in millet. Egg masses were detected in proso millet over a 7-d period in 1997 and a 4-d period in 1998. Larval sampling showed planting proso millet between late May and mid-June may maximize the presence of individuals from both O. nubilalis ecotypes. Once the optimal combination of planting date, plant density, and millet type is found, millet may serve as an effective refuge or trap crop for O. nubilalis management.

Two-legged hopping in autism spectrum disorders.

Sensory processing deficits are common within autism spectrum disorders (ASD). Deficits have a heterogeneous dispersion across the spectrum and multimodal processing tasks are thought to magnify integration difficulties. Two-legged hopping in place in sync with an auditory cue (2.3, 3.0 Hz) was studied in a group of six individuals with expressive language impaired ASD (ELI-ASD) and an age-matched control group. Vertical ground reaction force data were collected and discrete Fourier transforms were utilized to determine dominant hopping cadence. Effective leg stiffness was computed through a mass-spring model representation. The ELI-ASD group were unsuccessful in matching their hopping cadence (2.21 ± 0.30 hops·s(-1), 2.35 ± 0.41 hops·s(-1)) to either auditory cue with greater deviations at the 3.0 Hz cue. In contrast, the control group was able to match hopping cadence (2.35 ± 0.06 hops·s(-1), 3.02 ± 0.10 hops·s(-1)) to either cue via an adjustment of effective leg stiffness. The ELI-ASD group demonstrated a varied response with an interquartile range (IQR) in excess of 0.5 hops·s(-1) as compared to the control group with an IQR < 0.03 hops·s(-1). Several sensorimotor mechanisms could explain the inability of participants with ELI-ASD to modulate motor output to match an external auditory cue. These results suggest that a multimodal gross motor task can (1) discriminate performance among a group of individuals with severe autism, and (2) could be a useful quantitative tool for evaluating motor performance in individuals with ASD individuals.

Gait analysis of teenagers and young adults diagnosed with autism and severe verbal communication disorders.

Both movement differences and disorders are common within autism spectrum disorders (ASD). These differences have wide and heterogeneous variability among different ages and sub-groups all diagnosed with ASD. Gait was studied in a more homogeneously identified group of nine teenagers and young adults who scored as "severe" in both measures of verbal communication and overall rating of Autism on the Childhood Autism Rating Scales (CARS). The ASD individuals were compared to a group of typically developing university undergraduates of similar ages. All participants walked a distance of 6-meters across a GAITRite (GR) electronic walkway for six trials. The ASD and comparison groups differed widely on many spatiotemporal aspects of gait including: step and stride length, foot positioning, cadence, velocity, step time, gait cycle time, swing time, stance time, and single and double support time. Moreover, the two groups differed in the percentage of the total gait cycle in each of these phases. The qualitative rating of "Body Use" on the CARS also indicated severe levels of unusual body movement for all of the ASD participants. These findings demonstrate that older teens and young adults with "severe" forms of Verbal Communication Impairments and Autism differ widely in their gait from typically developing individuals. The differences found in the current investigation are far more pronounced compared to previous findings with younger and/or less severely involved individuals diagnosed with ASD as compared to typically developing controls. As such, these data may be a useful anchor-point in understanding the trajectory of development of gait specifically and motor functions generally.

A quality improvement initiative using a novel travel survey to promote patient-centered counseling.

BACKGROUND: We sought to evaluate and provide better itinerary-specific care to precounseled travelers and to assess diseases occurring while traveling abroad by surveying a community population. An additional quality improvement initiative was to expand our post-travel survey to be a more valuable tool in gathering high-quality quantitative data. METHODS: From de-identified data collected via post-travel surveys, we identified a cohort of 525 patients for a retrospective observational analysis. We analyzed illness encountered while abroad, medication use, and whether a physician was consulted. We also examined itinerary variables, including continents and countries visited. RESULTS: The 525 post-travel surveys collected showed that the majority of respondents traveled to Asia (31%) or Africa (30%). The mean number of travel days was 21.3 (median, 14). Univariate analysis demonstrated a statistically significant increase of risk for general illness when comparing travel duration of less than 14 days to greater than 14 days (11.3% vs 27.7%, p < 0.001). Duration of travel was also significant with regard to development of traveler's diarrhea (TD) (p = 0.0015). Destination of travel and development of traveler's diarrhea trended toward significance. Serious illness requiring a physician visit was infrequent, as were vaccine-related complications. CONCLUSIONS: Despite pre-travel counseling, traveler's diarrhea was the most common illness in our cohort; expanded prevention strategies will be necessary to lower the impact that diarrheal illness has on generally healthy travelers. Overall rates of illness did not vary by destination; however, there was a strong association between duration of travel and likelihood of illness. To further identify specific variables contributing to travel-related disease, including patient co-morbidities, reason for travel, and accommodations, the post-travel survey has been modified and expanded. A limitation of this study was the low survey response rate (18%); to improve the return rate, we plan to implement supplemental modalities including email and a web-based database.

Prioritizing partners across the continuum.

With the advent of accountable care organizations, bundled payments, value-based purchasing, and penalties for preventable hospital readmission, tight connections and collaboration across the care continuum will become critical to achieve successful patient outcomes and to reduce the cost of care delivery. Lehigh Valley Health Network (LVHN), the largest provider of health services in eastern Pennsylvania, set out on a journey to build collaborative relationships with skilled nursing facilities (SNFs) in their eastern Pennsylvania community. LVHN desired SNF partners with mutual interests in improving quality of care and lowering costs of delivery where possible. Recognizing that not all SNFs are alike, LVHN developed a Collaborative Partner Prioritization Tool to assess and prioritize skilled nursing facilities in an effort to determine those that would make the best collaborators. SNFs were reviewed based on their volume of mutual patients, quality of care delivery, and their perceived willingness to align with LVHN. Six variables were used to assess these facilities, including (1) patient discharge destination volume by SNF; (2) 30-day all-cause readmission rate to an LVHN hospital; (3) Medicare's Nursing Home Compare 5-Star Overall Rating; (4) the health network affiliation of the SNF's medical director; (5) the level of LVHN-employed or -affiliated physician presence at the SNF; and (6) the SNF's current participation in LVHN-sponsored programs and meetings. Through use of the Collaborative Partner Prioritization Tool, it was discovered that roughly 70% of LVHN patients who required skilled nursing care following their inpatient stay received care at 1 of 20 SNFs. Of these, 5 facilities performed well on the 6-variable assessment, deeming them the "Tier 1 Facilities" to initially focus collaborative efforts. LVHN has strategically deployed physician resources and has increased physician presence at these "Tier 1 SNFs." These facilities have also gained remote read-only access to LVHN's inpatient electronic medical record and have had opportunity to participate in LVHN-sponsored programs. Special projects have been co-developed with several SNFs, including a telemedicine-based Parkinson's disease program to increase patient access to a neurologist specially trained in movement disorders. The Collaborative Partner Prioritization Tool has become a powerful tool when used for prioritization of relationships and allocation of LVHN physicians and resources. Collaboration with strong SNF partners has offered a shared opportunity to improve quality of care, reduce costs, and prepare for the many policies affecting the health care industry. Future outcomes of this work will include quality metrics, such as readmissions, patient satisfaction with care, time for decision to admit, and overall costs of care. The data and metrics used to define the prioritization tool will continue to be adapted as the post-acute market and hospital-SNF relationships continue to evolve.

Inconspicuous consumption.

The 1990s were a decade of less flash and more cash for life's big and little necessities. Tracking the Consumer Expenditure Survey reveals how our shifting tastes and changing demographics are transforming the way we spend.