Confirmation and variability of the Allee effect inDictyostelium discoideumcell populations, possible role of chemical signaling within cell clusters.

In studies of the unicellular eukaryoteDictyostelium discoideum, many have anecdotally observed that cell dilution below a certain 'threshold density' causes cells to undergo a period of slow growth (lag). However, little is documented about the slow growth phase and the reason for different growth dynamics below and above this threshold density. In this paper, we extend and correct our earlier work to report an extensive set of experiments, including the use of new cell counting technology, that set this slow-to-fast growth transition on a much firmer biological basis. We show that dilution below a certain density (around 104cells ml-1) causes cells to grow slower on average and exhibit a large degree of variability: sometimes a sample does not lag at all, while sometimes it takes many moderate density cell cycle times to recover back to fast growth. We perform conditioned media experiments to demonstrate that a chemical signal mediates this endogenous phenomenon. Finally, we argue that while simple models involving fluid transport of signal molecules or cluster-based signaling explain typical behavior, they do not capture the high degree of variability between samples but nevertheless favor an intra-cluster mechanism.

Predictors of 30-day readmission in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cross-sectional database study.

BACKGROUND: The predictors of readmission in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have not been characterized. OBJECTIVE: To determine the variables predictive of 30-day readmission after SJS/TEN hospitalization. METHODS: We performed a cross-sectional study of the 2010-2014 Nationwide Readmissions Database. Bivariate and multivariable logistic regression was used to evaluate associations of patient demographics, comorbidities, and hospital characteristics with readmission. Aggregate and per-readmission costs were calculated. RESULTS: There were 8837 index admissions with SJS/TEN reported; of these, 910 (10.3%) were readmitted, with diagnoses including systemic infection (22.0%), SJS/TEN (20.6%), and cutaneous infection (9.1%). Associated characteristics included age 45 to 64 years (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.43-2.49), Medicaid insurance (OR, 1.83; 95% CI, 1.48-2.27), and nonmetropolitan hospital admission (OR, 1.67; 95% CI, 1.31-2.13). Associated comorbidities included HIV/AIDS (OR, 2.48; 95% CI, 1.63-3.75), collagen vascular disease (OR, 2.38; 95% CI, 1.88-3.00), and metastatic cancer (OR, 2.16; 95% CI, 1.35-3.46). The median per-readmission cost was $10,019 (interquartile range, $4,788-$16,485). LIMITATIONS: The Nationwide Readmissions Database lacks the ability to track the same patient across calendar years. The diagnostic code lacks specificity for hospitalizations <3 days. CONCLUSIONS: Thirty-day readmissions after SJS/TEN hospitalizations are common. Dedicated efforts to identify at-risk patients may improve peridischarge continuity.

Dermatology-specific and all-cause 30-day and calendar-year readmissions and costs for dermatologic diseases from 2010 to 2014.

BACKGROUND: Readmissions for skin disease, particularly for the same diagnosis and over time, have not been well studied. OBJECTIVE: To characterize hospital readmissions for skin disease. METHODS: A cross-sectional observational study examined the Nationwide Readmissions Database from 2010 to 2014, a national sample of hospital discharges in the United States. RESULTS: Of the patients in 3,602,599 dermatologic hospitalizations from 2010 to 2014, 9.8% were readmitted for any cause, 3.3% were admitted for the same diagnosis within 30 days, and 7.8% were readmitted for the same diagnosis within the calendar year (CY). The cost of all CY same-cause readmissions was $508 million per year. Mycosis fungoides had the highest 30-day all-cause readmission rate (32%), vascular hamartomas and dermatomyositis had the highest 30-day same-cause readmission rates (21% and 18%, respectively), and dermatomyositis and systemic lupus erythematosus had the highest CY same-cause readmission rates (31% and 24%, respectively). Readmission rates stayed stable from 2010 to 2014. Readmission for the same diagnosis was strongly associated with Medicaid and morbid obesity. LIMITATIONS: This study is a broad description of hospitalizations for skin disease. Conclusions for individual diseases are not intended. CONCLUSION: The rates and costs of readmissions for skin diseases remained high from 2010 to 2014. This study identifies diseases associated with high risk of hospital readmission, but disease-specific studies are needed. The diseases and risk factors presented should guide additional studies focused on strategies to reduce readmissions in specific skin diseases.

Trends and Scope of Dermatology Procedures Billed by Advanced Practice Professionals From 2012 Through 2015.

Importance: Advanced practice professionals (APPs) such as nurse practitioners and physician assistants independently perform a large number and variety of dermatologic procedures, but little is known about how the number and scope of these procedures have changed over time. Objective: To examine the trends in scope and volume of dermatology procedures billed by APPs over time. Design, Setting, and Participants: A longitudinal study was conducted using the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File from 2012 through 2015. The data encompass nearly all outpatient procedures paid by Medicare Part B in the United States and include the type of clinician under which procedures were billed. Main Outcomes and Measures: For each type of dermatology procedure, the total number performed by APPs and the total number performed by dermatologists each year. Results: The total number (and percentage) of all dermatologic procedures performed by APPs increased from 2.69 million of 30.7 million (8.8%) in 2012 to 4.54 million of 33.9 million (13.4%) in 2015. The most common procedures performed by APPs in 2015 were destructions of benign neoplasms (3.6 million), biopsies (788 834), and destructions of malignant neoplasms (48 982). The numbers of patch tests, removals of benign and malignant neoplasms, intermediate and complex repairs, flaps, and surgical pathologic specimen examinations by APPs also increased each year from 2012 through 2015. Conclusions and Relevance: The number and scope of dermatologic procedures performed by APPs appear to be increasing over time. These procedures can be difficult and invasive. This study suggests that further studies are needed to determine what association these procedures have with patient outcomes and the potential need for more formal training.

Characterization of the 2016-2017 Dermatology Standardized Letter of Recommendation.

Objective: We aimed to analyze the reformatted standard letter of recommendation (SLOR) for dermatology residents to examine trends in grading and content based on the positions of the letter writers, their backgrounds, and their relationship with the applicant, as well as to evaluate the SLOR's ability to discriminate applicants. Design: This was a retrospective characterization study of dermatology SLORs from the 2016-17 application cycle. Setting: We examined SLORs received by The Ohio State University, the University of Oklahoma, and Hofstra University Northwell Health dermatology residency programs. Participants: We included dermatology residency applicants and their letter writers from the 2016-17 application cycle. Results: A total of 141 SLORs were analyzed from 115 applicants. SLORs demonstrated grade inflation from letter writers of all backgrounds. Ratings for research potential and inquisitive nature were significantly lower than ratings for other categories. Letter writers with limited clinical and research contact graded applicants significantly lower than did writers who had more extensive contact. Word boxes were underutilized. Conclusion: The dermatology SLOR is useful in differentiating applicants, and ratings correlate with the relationships that letter writers have with their applicants. Residency programs should be aware of these findings when evaluating letters of recommendation for applicants.

Folate and phototherapy: What should we inform our patients?

BACKGROUND: Ultraviolet (UV) degradation of folate has been studied in vitro and in vivo, but comprehensive reviews of the subject and recommendations for supplementing folate are lacking, especially for women of childbearing age, in whom decreases in folate predisposes newborns to neural tube defects. OBJECTIVE: We reviewed the effects of phototherapy on folate and provide a recommendation for women of childbearing age on phototherapy. METHODS: PubMed was searched for in vivo studies comparing folate levels before and after phototherapy. RESULTS: There is no evidence of decreased folate levels after UVA exposure. Decreased folate levels after sun exposure were limited to subjects taking folate supplements. Studies using narrowband UVB showed mixed results, potentially explained by dose-dependent degradation of folate; exposure >40 J/cm2 cumulatively and >2 J/cm2 per treatment were associated with 19%-27% decreases in serum folate levels, while lower doses did not affect folate levels. LIMITATIONS: Extensive variability in results from studies and lack of considering confounders. CONCLUSIONS: We recommend all women of childbearing age on phototherapy take 0.8 mg/day of folate supplements, as suggested by current guidelines for women of childbearing age, to reduce the risk of neural tube defects in unplanned pregnancy.

The association between bullous pemphigoid and neurological disorders: a systematic review.

Studies suggest an association between neurological disorders and bullous pemphigoid. The goal of this systematic review was to characterize the occurrence of neurological disorders in patients with bullous pemphigoid. We performed a systematic review of the current English literature from 1984 to June 1st, 2015 for documented cases of coexistent BP and neurological disorders. The literature search resulted in 53 articles meeting the inclusion criteria. Patients with bullous pemphigoid had an increased risk of stroke (OR: 4.43 [95% CI: 2.69-7.28]; p<0.001), dementia (OR: 5.48 [95% CI: 3.26-9.23]; p<0.001), Parkinson's (OR: 3.06 [95% CI: 1.97-4.77]; p< 0.001), and epilepsy/seizures (OR: 22.88 [95% CI: 2.64-198.21]; p = 0.0045). Neurological disorders preceded bullous pemphigoid in the majority of cases with a mean time interval of 6.7 years. The one-year mortality was increased in bullous pemphigoid patients who had concomitant stroke (OR: 2.87 [95% CI: 1.67-4.96]; p<0.001). Bullous pemphigoid patients have an increased association with neurological disorders which may increase mortality.

Prescription patterns and costs of acne/rosacea medications in Medicare patients vary by prescriber specialty.

BACKGROUND: Prescription patterns for acne/rosacea medications have not been described in the Medicare population, and comparisons across specialties are lacking. OBJECTIVE: To describe the medications used for treating acne/rosacea in the Medicare population and evaluate differences in costs between specialties. METHODS: A cross-sectional study was performed of the 2008 and 2010 Centers for Medicare and Medicaid Services Prescription Drug Profiles, which contains 100% of Medicare part D claims. RESULTS: Topical antibiotics accounted for 63% of all prescriptions. Patients ≥65 years utilized more oral tetracycline-class antibiotics and less topical retinoids. Specialists prescribed brand name drugs for the most common topical retinoids and most common topical antibiotics more frequently than family medicine/internal medicine (FM/IM) physicians by 6%-7%. Topical retinoids prescribed by specialists were, on average, $18-$20 more in total cost and $2-$3 more in patient cost than the same types of prescriptions from FM/IM physicians per 30-day supply. Specialists (60%) and IM physicians (56%) prescribed over twice the rate of branded doxycycline than FM doctors did (27%). The total and patient costs for tetracycline-class antibiotics were higher from specialists ($18 and $4 more, respectively) and IM physicians ($3 and $1 more, respectively) than they were from FM physicians. LIMITATIONS: The data might contain rare prescriptions used for conditions other than acne/rosacea, and suppression algorithms might underestimate the number of specialist brand name prescriptions. CONCLUSION: Costs of prescriptions for acne/rosacea from specialists are higher than those from primary care physicians and could be reduced by choosing generic and less expensive options.

Association of Dermatology Consultations With Patient Care Outcomes in Hospitalized Patients With Inflammatory Skin Diseases.

Importance: The value of inpatient dermatology consultations has traditionally been demonstrated with frequency in changes of diagnosis and management; however, the impact of dermatology consultations on metrics such as hospital length of stay and readmission rates remains unknown. Objective: To determine the association of dermatology consultations with patient care in hospitalized patients using objective values. Design, Setting, and Participants: We retrospectively queried the deidentified database of patients hospitalized between January 1, 2012, and December 31, 2014, at a single university medical center. A total of 413 patients with a primary inflammatory skin condition discharge diagnosis and 647 patients with primary inflammatory skin condition admission diagnosis were selected. Main Outcomes and Measures: Hospital length of stay and 1-year readmission with inflammatory skin conditions. Results: The 413 patients with a primary inflammatory skin condition discharge diagnosis were 61.0% female and had a mean (SD) age of 55.1 (16.4) years. The 647 patients with primary inflammatory skin condition admission diagnosis were 50.8% female and had a mean (SD) age of 57.8 (15.9) years. Multivariable modeling showed that dermatology consultations were associated with a reduction of 1-year inflammatory skin condition readmissions among patients who were discharged primarily with an inflammatory skin condition (readmission probability, 0.0025; 95% CI, 0.00020-0.030 with dermatology consult vs 0.026; 95% CI, 0.0065-0.10 without; odds ratio, 0.093; 95% CI, 0.010-0.840; P = .03). No other confounding variable was associated with reduction in readmissions. Multivariable modeling also showed that dermatology consultations were associated with a reduction in the adjusted hospital length of stay by 2.64 days (95% CI, 1.75-3.53 days; P < .001). Conclusions and Relevance: Dermatology consultations were associated with improvements of outcomes among hospitalized patients. The expansion of the role of dermatology consultation services may improve patient care in a cost-effective manner.

The cost of topical immunomodulator therapy in Medicare patients varies by prescriber specialty.

BACKGROUND: Topical immunomodulators (TI)-including corticosteroids, calcineurin inhibitors, and vitamin D analogues-are commonly prescribed in multiple specialties, but cost comparisons are lacking. OBJECTIVE: To evaluate differences in costs of TI across specialties and determine associated variables. METHODS: A cross-sectional study was performed using the Centers for Medicare & Medicaid Services 2008 and 2010 Prescription Drug Public Use Profiles, which contain 100% of drug claims made by Medicare beneficiaries. RESULTS: Branded drugs cost an average of $174.02 more than generics per 30-day supply (P < .001). Differences in health insurance benefit phase, drug choice, brand name, and coverage type were the greatest determinants of patient cost (P < .001). Prescriptions for low-, medium-, and high-potency TI from specialists (mostly dermatologists) cost more than those from family medicine, internal medicine, and psychiatry/neurology physicians; total costs of a 30-day supply from a specialist differed from family and internal medicine physicians by $7.36-$14.57, and patient costs were higher for specialists by $1.69-$3.16 (P < .01). Brand names were prescribed 8% of the time by specialists and 1.4%-3.1% by nonspecialists. LIMITATIONS: We were unable to adjust for some confounders of cost, such as medication weight or treated body area, and the data does not reflect previous treatment failures or use by non-Medicare patients. CONCLUSION: The costs of TIs prescribed by specialists (primarily dermatologists) are higher than those prescribed by primary care physicians and could be reduced by choosing more generics within the respective potency classes.

Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients.

BACKGROUND: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS. METHODS: We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05. RESULTS: Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004). CONCLUSIONS: The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.

Functional magnetic resonance imaging networks induced by intracranial stimulation may help defining the epileptogenic zone.

Patients with medically intractable epilepsy often undergo invasive evaluation and surgery, with a 50% success rate. The low success rate is likely due to poor identification of the epileptogenic zone (EZ), the brain area causing seizures. This work introduces a new method using functional magnetic resonance imaging (fMRI) with simultaneous direct electrical stimulation of the brain that could help localize the EZ, performed in five patients with medically intractable epilepsy undergoing invasive evaluation with intracranial depth electrodes. Stimulation occurred in a location near the hypothesized EZ and a location away. Electrical recordings in response to stimulation were recorded and compared to fMRI. Multiple stimulation parameters were varied, like current and frequency. The brain areas showing fMRI response were compared with the areas resected and the success of surgery. Robust fMRI maps of activation networks were easily produced, which also showed a significant but weak positive correlation between quantitative measures of blood-oxygen-level-dependent (BOLD) activity and measures of electrical activity in response to direct electrical stimulation (mean correlation coefficient of 0.38 for all acquisitions that produced a strong BOLD response). For four patients with outcome data at 6 months, successful surgical outcome is consistent with the resection of brain areas containing high local fMRI activity. In conclusion, this method demonstrates the feasibility of simultaneous direct electrical stimulation and fMRI in humans, which allows the study of brain connectivity with high resolution and full spatial coverage. This innovative technique could be used to better define the localization and extension of the EZ in intractable epilepsies, as well as for other functional neurosurgical procedures.

Low consistency of four brain connectivity measures derived from intracranial electrode measurements.

Measures of brain connectivity are currently subject to intense scientific and clinical interest. Multiple measures are available, each with advantages and disadvantages. Here, we study epilepsy patients with intracranial electrodes, and compare four different measures of connectivity. Perhaps the most direct measure derives from intracranial electrodes; however, this is invasive and spatial coverage is incomplete. These electrodes can be actively stimulated to trigger electrophysical responses to provide the first measure of connectivity. A second measure is the recent development of simultaneous BOLD fMRI and intracranial electrode stimulation. The resulting BOLD maps form a measure of effective connectivity. A third measure uses low frequency BOLD fluctuations measured by MRI, with functional connectivity defined as the temporal correlation coefficient between their BOLD waveforms. A fourth measure is structural, derived from diffusion MRI, with connectivity defined as an integrated diffusivity measure along a connecting pathway. This method addresses the difficult requirement to measure connectivity between any two points in the brain, reflecting the relatively arbitrary location of the surgical placement of intracranial electrodes. Using a group of eight epilepsy patients with intracranial electrodes, the connectivity from one method is compared to another method using all paired data points that are in common, yielding an overall correlation coefficient. This method is performed for all six paired-comparisons between the four methods. While these show statistically significant correlations, the magnitudes of the correlation are relatively modest (r (2) between 0.20 and 0.001). In summary, there are many pairs of points in the brain that correlate well using one measure yet correlate poorly using another measure. These experimental findings present a complicated picture regarding the measure or meaning of brain connectivity.

Logical foundations and fast implementation of probabilistic tractography.

Although tractography can noninvasively map axonal pathways, current approaches are typically incomplete or computationally intensive. Fast, complete maps may serve as a useful clinical tool for assessing neurological disorders stemming from pathological anatomical connections such as epilepsy. We re-frame tractography in terms of logic and conditional probabilities. The formalism inherently includes global constraints and can compute connections between any two arbitrary regions of the brain. The formalism also lends itself to a fast implementation using standard partial differential equation solvers, which makes whole-brain probabilistic maps of anatomical connectivity feasible. We demonstrate results of our implementation on in vivo data and show that it outperforms Monte Carlo approaches in both computation time and identification of pathways.