A 47-Year-Old Man with Fever and Rash.

A 47-Year-Old Man with Fever and RashA 47-year-old man presented for evaluation of fevers, rash, and diffuse muscle aches. How do you approach the evaluation, and what is the differential diagnosis?

Appropriateness of peripherally inserted central catheter use among general medical inpatients: an observational study using routinely collected data.

BACKGROUND: Peripherally inserted central catheters (PICC) are among the most commonly used medical devices in hospital. This study sought to determine the appropriateness of inpatient PICC use in general medicine at five academic hospitals in Toronto, Ontario, Canada, based on the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC). METHODS: This was a retrospective, cross-sectional study of general internal medicine patients discharged between 1 April 2010 and 31 March 2015 who received a PICC during hospitalisation. The primary outcomes were the proportions of appropriate and inappropriate inpatient PICC use based on MAGIC recommendations. Hospital administrative data and electronic clinical data were used to determine appropriateness of each PICC placement. Multivariable regression models were fit to explore patient predictors of inappropriate use. RESULTS: Among 3479 PICC placements, 1848 (53%, 95% CI 51% to 55%) were appropriate, 573 (16%, 95% CI 15% to 18%) were inappropriate and 1058 (30%, 95% CI 29% to 32%) were of uncertain appropriateness. The proportion of appropriate and inappropriate PICCs ranged from 44% to 61% (p<0.001) and 13% to 21% (p<0.001) across hospitals, respectively. The most common reasons for inappropriate PICC use were placement in patients with advanced chronic kidney disease (n=500, 14%) and use for fewer than 15 days in patients who are critically ill (n=53), which represented 14% of all PICC placements in the intensive care unit. Patients who were older, female, had a Charlson Comorbidity Index score greater than 0 and more severe illness based on the Laboratory-based Acute Physiology Score were more likely to receive an inappropriate PICC. CONCLUSIONS: Clinical practice recommendations can be operationalised into measurable domains to estimate the appropriateness of PICC insertions using routinely collected hospital data. Inappropriate PICC use was common and varied substantially across hospitals in this study, suggesting that there are important opportunities to improve care.

Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study.

BACKGROUND: Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. METHODS: In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. RESULTS: Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. INTERPRETATION: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.

Associations among socioeconomic status, patterns of care and outcomes in breast cancer patients in a universal health care system: Ontario's experience.

BACKGROUND: The Canadian health care system provides equitable access to equivalent standards of care. The authors investigated to determine whether patients with breast cancer who had different socioeconomic status (SES) received different care and had different overall survival (OS) in Ontario, Canada. METHODS: Women who were diagnosed with breast cancer between 2004 and 2009 were identified from the Ontario Cancer Registry and linked to provincial databases to ascertain patient demographics, screening, diagnosis, treatment patterns, and survival. SES was defined as neighborhood income by postal code and was divided into income quintiles (Q1-Q5; with Q5 the highest SES quintile). Univariable and multivariable analyses were used to examine the associations between: 1) SES and mammogram screening and breast cancer treatments, and 2) SES and OS. RESULTS: In total, 34,776 patients with breast cancer who had information on disease stage available at diagnosis were identified. Seventy-six percent of women were aged >50 years. Patients with higher SES were more likely to be diagnosed at an earlier stage (Q5 [44.3%] vs Q1 [37.7%]; odds ratio [OR], 1.31; 95% confidence interval [CI], 1.23-1.41; P < .0001) and also were more likely to receive adjuvant chemotherapy (Q5 vs Q1: OR, 1.18; 95% CI, 1.10-1.26; P < .0001) and radiotherapy (Q5 vs Q1: OR, 1.24; 95% CI, 1.15-1.33; P < .0001). The 5-year OS rates for Q1 through Q5 were 80%, 81%, 82.2%, 83.9%, and 85.7%, respectively (P < .0001). After adjusting for patient demographics, cancer stage at diagnosis, adjuvant chemotherapy, trastuzumab, radiotherapy and surgery types, higher SES remained associated with better OS (P = .0017). CONCLUSIONS: In a universal health care system, higher SES is associated with greater screening and treatments and with better OS after adjusting for screening, cancer stage at diagnosis, and treatments.

A Systematic Review and Network Meta-Analysis of Biologic Agents in the First Line Setting for Advanced Colorectal Cancer.

BACKGROUND: Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab (BEV) are used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have directly compared their relative efficacy on progression-free survival (PFS) and overall survival (OS). METHODS: We conducted a systematic review of first-line RCTs comparing (1) EGFRis vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs. chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using Cochrane methodology. Data on and PFS and OS were extracted using the Parmar method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were conducted to estimate the direct, indirect and combined PFS and OS hazard ratios (HRs) comparing EGFRis to BEV. RESULTS: Seventeen RCTs contained extractable data for quantitative analysis. Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR = 0.91 (95% CR: 0.75-1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV. Meta-analysis of OS using direct evidence, largely influenced by one trial, showed an improvement with EGFRis therapy (HR = 0.79 (95% CR: 0.65-0.98)), while indirect and combined NMA of OS did not show a difference between EGFRis and BEV Successive inclusions of trials over time in the combined NMA did not show superiority of EGFRis over BEV. CONCLUSIONS: Our findings did not support OS or PFS benefits of EGFRis over BEV in first-line mCRC.

Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis.

BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC. METHODS: We performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS. RESULTS: Twenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71-1.34). For N-CRT versus CRT, the HR was 1.03 (0.69-1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64-1.48). CONCLUSIONS: Adjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups.

High-throughput generation of hydrogel microbeads with varying elasticity for cell encapsulation.

Elasticity of cellular microenvironments strongly influences cell motility, phagocytosis, growth and differentiation. Currently, the relationship between the cell behaviour and matrix stiffness is being studied for cells seeded on planar substrates, however in three-dimensional (3D) microenvironments cells may experience mechanical signalling that is distinct from that on a two-dimensional matrix. We report a microfluidic approach for high-throughput generation of 3D microenvironments with different elasticity for studies of cell fate. The generation of agarose microgels with different elastic moduli was achieved by (i) introducing into a microfluidic droplet generator two streams of agarose solutions, one with a high concentration of agarose and the other one with a low concentration of agarose, at varying relative volumetric flow rate ratios of the two streams, and (ii) on-chip gelation of the precursor droplets. At 37 degreesC, the method enabled a approximately 35-fold variation of the shear elastic modulus of the agarose gels. The application of the method was demonstrated by encapsulating two mouse embryonic stem cell lines within the agarose microgels. This work establishes a foundation for the high-throughput generation of combinatorial microenvironments with different mechanical properties for cell studies.

Electrochemical sensing in paper-based microfluidic devices.

This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, microPEDs). The microPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the microPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.

A microfluidic approach to chemically driven assembly of colloidal particles at gas-liquid interfaces.

Bubbling up: Dissolution of CO(2) bubbles in a suspension of colloidal particles chemically induces the assembly of particles on the surface of shrunken bubbles, and thus yields rapid continuous formation of a colloidal armor. This approach maintains the high colloidal stability of particles in bulk, has increased productivity, and allows the formation of bubbles with precisely controlled dimensions.