Fungal Orbital Cellulitis: Presenting Features,Management and Outcomes at a Referral Center

Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center.

Methods: Retrospective case series.

Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn’s disease. Another patient had a history of alcoholic liver cirrhosis, Crohn’s disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization.

Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.     

Economic Burden of Opioid-Induced Constipation Among Long-Term Opioid Users with Noncancer Pain

Background

Opioid-induced constipation (OIC) can be a debilitating side effect of opioid therapy and may result in increased medical costs. The published data on the economic burden of OIC among long-term opioid users are limited.

Objective

To assess the economic burden of OIC in patients with noncancer pain in a managed care population in the United States.

Methods

This retrospective study used 2007–2011 data from the Truven Health MarketScan Commercial and Medicare databases. The study included adults with ≥12 months of insurance enrollment before and after starting long-term (≥90 days) use of opioids. Patients were excluded if they had cancer or a diagnosis of drug abuse or drug dependence during the study period, or if they had constipation or bowel obstruction within 90 days before starting opioid therapy during the study period. OIC was identified by International Classification of Diseases, Ninth Edition codes for constipation (564.0) or bowel obstruction (560.x) within 12 months of the initiation of an opioid. Patients with OIC were identified in the nonelderly, elderly (age ≥65 years), and long-term care populations. Differences in costs and healthcare resource utilization were calculated using propensity scoring.

Results

A total of 13,808 nonelderly (age, 48.6 ± 10.4 years; female, 50%) and 2958 elderly patients (age, 78.7 ± 8.1 years; female, 70%) met the study inclusion criteria. Of 401 nonelderly and 194 elderly patients with OIC, 85 patients initiated opioid therapy in a long-term care facility (age, 80.7 ± 11.6 years; female, 77%). After matching by key covariates, patients with OIC had significantly more hospital admissions than patients without OIC (nonelderly, 33% vs 22%, respectively; P <.001; elderly, 51% vs 31%, respectively; P <.001) and longer inpatient stays (nonelderly, 3.0 ± 8.4 days vs 1.0 ± 3.0 days, respectively; P <.001; elderly, 5.2 ± 12.2 days vs 2.1 ± 4.0 days, respectively; P <.001). The group with OIC had significantly higher total healthcare costs than the group without OIC in all 3 study cohorts (nonelderly, $23,631 ± $67,209 vs $12,652 ± $19,717, respectively; elderly, $16,923 ± $38,191 vs $11,117 ± $19,525, respectively; long-term care, $16,000 ± $22,897 vs $14,437 ± $25,690, respectively; all P <.05).

Conclusion

To the best of our knowledge, this is the first study to analyze the economic impact of long-term use of opioids among patients with OIC, using real-world data. The findings underscore the significant economic burden associated with long-term opioid use for noncancer pain in a managed care population. Effective therapies for OIC may reduce the associated economic burden and improve quality of life for long-term opioid users.     

Insights in Public Health: Initiating Bicycle Sharing in Hawai‘i: Lessons Learned from a Small Pilot Bike Share Program

In 2011, a small pilot bike share program was established in the town core of Kailua, Hawai‘i, with funding from the Hawai‘i State Department of Health. The Kailua system consisted of two stations with 12 bicycles, and the goal was to secure additional funding to expand the station network in the future. Community feedback consistently indicated support for the bike share program. However, system metrics showed low levels of usage, averaging 41.5 rides per month (2011–2014). From observational data, users were primarily tourists. With minimal local staff, the bike share program had limited resources for promotion and education, which may have hindered potential use by local residents. Management of station operations and bike maintenance were additional, ongoing barriers to success. Despite the challenges, the pilot bike share program was valuable in several ways. It introduced the bike share concept to Hawai‘i, thereby helping to build awareness and connect an initial network of stakeholders. Furthermore, the pilot bike share program informed the development of a larger bike share program for urban Honolulu. As limited information exists in the literature about the experiences of smaller bike share programs and their unique considerations, this article shares lessons learned for other communities interested in starting similar bike share programs.     

Divergent outcomes of gut microbiota alteration upon use of spectrum antibiotics in high sugar diet-induced diabetes in rats

Background: A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration. Gut dysbiosis increases lipopolysaccharide (LPS) and reduces propionate and butyrate levels to impair the insulin signalling cascades by different molecular pathways, which progresses into IR. The present study was designed to investigate the effect of spectrum specific antibiotics on the modulation of gut microbiota and its signalling pathways to prevent diet-induced diabetes. Methods: Healthy male Wistar rats were divided into a non-diabetic group with a control diet (CD), a diabetic group with a high sucrose diet (HSD) and two antibiotic fed groups (linezolid and cefdinir; administered by oral gavage) along HSD. Physiological, biochemical, inflammatory and microbiome parameters were examined. Results: Cefdinir administration in HSD rats reduced fasting glucose, serum triglyceride, and cholesterol levels compared to HSD alone. In addition, cefdinir reduced serum LPS by decreasing the population of Gram-negative phyla, that is, Bacteroidetes and Proteobacteria in the fecal content. Furthermore, cefdinir treatment decreased hepatic/ileal/colonic Tlr4, Nlr1, and Nf-κB at the mRNA level. Moreover, cefdinir-treated rats had shown increased fecal butyrate and propionate and reduced acetate levels compared to HSD alone. Cefdinir treatment also induced ileal/colonic Gpr43 and Glut4 at the mRNA level after 12 weeks of administration. Conclusions: Taken together, these data suggest that administration of a Gram-negative spectrum antibiotic, that is, cefdinir, has modulated the gut microbiota, and reduced serum LPS and triglycerides, which prevented the progression of IR and inflammation in HSD rats.

A sugar rich diet induces inflammation and insulin resistance (IR) mainly through gut microbiota alteration.     

A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital

Aim:Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs. The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease.Results:Compared to unfractionated heparin group of patients, the average prothrombin time was significantly higher (P < 0.0001) whereas hypokalemia was significantly lower (P < 0.02) in enoxaparin group of patients. Even though recurrence of angina and ADRs such as bleeding, nausea, headache and sudden cough occurred less frequently in the enoxaparin group of patients compared to unfractionated heparin group of patients, the differences were not significant.Conclusions:Antithrombotic therapy with enoxaparin plus aspirin was safer and more effective than unfractionated heparin plus aspirin, in reducing the incidence of ischemic events in patients with unstable angina or myocardial infarction in the early phase.KEY WORDS: Anticoagulant, coronary heart disease, enoxaparin, safety, and efficacy, unfractionated heparin     

Modelling the time course of antimalarial parasite killing: a tour of animal and human models,translation and challenges

Malaria remains a global public health concern and current treatment options are suboptimal in some clinical settings. For effective chemotherapy, antimalarial drug concentrations must be sufficient to remove completely all of the parasites in the infected host. Optimized dosing therefore requires a detailed understanding of the time course of antimalarial response, whilst simultaneously considering the parasite life cycle and host immune elimination. Recently, the World Health Organization (WHO) has recommended the development of mathematical models for understanding better antimalarial drug resistance and management. Other international groups have also suggested that mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) models can support the rationalization of antimalarial dosing strategies. At present, artemisinin-based combination therapy (ACT) is recommended as first line treatment of falciparum malaria for all patient groups. This review summarizes the PK–PD characterization of artemisinin derivatives and other partner drugs from both preclinical studies and human clinical trials. We outline the continuous and discrete time models that have been proposed to describe antimalarial activity on specific stages of the parasite life cycle. The translation of PK–PD predictions from animals to humans is considered, because preclinical studies can provide rich data for detailed mechanism-based modelling. While similar sampling techniques are limited in clinical studies, PK–PD models can be used to optimize the design of experiments to improve estimation of the parameters of interest. Ultimately, we propose that fully developed mechanistic models can simulate and rationalize ACT or other treatment strategies in antimalarial chemotherapy.