In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 g/ml for doxycycline and 8 g/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 g/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 g/ml to levels below that achieved by 0.25 g of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycyclinesusceptible and -resistant strains of R. tsutsugamushi.

Background There are no recognized pharmacological treatments for abdominal aortic aneurysms ( AAA ), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30‐day mortality. Methods and Results We conducted a systematic review and meta‐analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE , and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I 2 statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case‐control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P =0.001, I 2 =86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P <0.0001, I 2 =27%), and preoperative statin use was associated with a lower 30‐day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P =0.005, I 2 =57%). Conclusions Statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients. Clinical Trial Registration URL : http://www.crd.york.ac.uk . Unique identifier: CRD 42017056480.

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This population-based cohort study compares long-term outcomes of elective endovascular aortic repair vs open surgical repair of abdominal aortic aneurysm among patients 40 years and older in Ontario, Canada.

I ndividuals with diabetes or peripheral artery disease share a common fear: leg amputation. Frequently synergistic, peripheral neuropathy and arterial insufficiency predispose patients to foot ulceration, tissue death and infection. 1,2 Diabetic foot ulcers are estimated to occur at a rate of 2%-4% per annum among individuals with diabetes in developed countries, 3 and the numbers are continuing to rise. 4 About one-third of diabetic foot ulcers fail to heal 5 and many patients with nonhealing ulcers progress to lower-extremity amputation, with 1 diabetes-related lowerextremity amputation occurring every 30 seconds worldwide. 3 When blood flow is sufficiently restricted to produce constant foot pain or gangrene, patients with peripheral artery disease have a 1-year mortality rate of 22% and a 1-year major amputation rate of 22%. 6 Together, peripheral artery disease and diabetes account for more than 80% of lower-extremity amputations in Canada. 7,8 Emerging data show that several diabetes-related complications, such as acute myocardial infarction, stroke, end-stage renal disease and hyperglycemia crisis, have declined over the last 20 years, 9 likely owing to improvements in pharmacotherapy and processes of care. Furthermore, hospital admissions for cardiovascular disease have declined by 54% between 1994 and 2014 in Ontario, Canada. 10 However, foot complications of diabetes and peripheral artery disease respond poorly to pharmacotherapy, and amputation-prevention efforts remain disjointed. 11 It is unclear whether declines have occurred in rates of lowerextremity amputations related to diabetes and peripheral artery

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Because the quantity of rickettsiae injected into the mice was comparable to the quantity reported in the literature for human blood during natural infections, scrub typhus could present a risk in blood collected from donors in endemic areas. This may especially be true, because people can be rickettsemic before illness, after successful antibiotic treatment, and chronically after resolution of disease.

Objective Diabetic foot ulcer, which often leads to lower limb amputation, is a devastating complication of diabetes that is a major burden on patients and the healthcare system. The main objective of this study is to determine the economic burden of diabetic foot ulcer-related care. Methods We conducted a multicenter study of all diabetic foot ulcer patients admitted to general internal medicine wards at seven hospitals in the Greater Toronto Area, Canada from 2010 to 2015, using the GEMINI database. We compared the mean costs of care per patient for diabetic foot ulcer-related admissions, admissions for other diabetes-related complications, and admissions for the top five most costly general internal medicine conditions, using the Ontario Case Costing Initiative. Regression models were used to determine adjusted estimates of cost per patient. Propensity-score matched analyses were performed as sensitivity analyses. Results Our study cohort comprised of 557 diabetic foot ulcer patients; 2939 non-diabetic foot ulcer diabetes patients; and 23,656 patients with the top 5 most costly general internal medicine conditions. Diabetic foot ulcer admissions incurred the highest mean cost per patient ($22,754) when compared to admissions with non-diabetic foot ulcer diabetes ($8,350) and the top five most costly conditions ($10,169). Using adjusted linear regression, diabetic foot ulcer admissions demonstrated a 49.6% greater mean cost of care than non-diabetic foot ulcer-related diabetes admissions (95% CI 1.14–1.58), and a 25.6% greater mean cost than the top five most costly conditions (95% CI 1.17–1.34). Propensity-scored matched analyses confirmed these results. Conclusion Diabetic foot ulcer patients incur significantly higher costs of care when compared to admissions with non-diabetic foot ulcer-related diabetes patients, and the top five most costly general internal medicine conditions.