Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case–control study

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case–control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25–90), and 40 (67 %) were male. Most patients had osteomyelitis (82 %), predominantly from a contiguous source (87 %). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50 %) vs. 4 (20 %); p?=?0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55 %) vs. 5 (25 %); p?=?0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p?=?0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2–36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75 %) vs. 27 (68 %); p?=?0.8] and 6 months [14 (70 %) vs. 23 (58 %); p?=?0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5 %) vs. 7 (18 %); p?=?0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.     

The effect of bicarbonate on photosynthetic oxygen evolution in flashing light in chloroplast fragments

The ability of bicarbonate ion (HCO₃^-) to stimulate photosynthetic oxygen evolution in maize chloroplast fragments exposed to continuous light depends on light intensity. Stimulation by HCO₃^- is less at low intensities. In HCO₃^--depleted chloroplasts exposed to brief saturating light flashes, period 4 oscillations (in O₂ yield per flash) are damped within three cycles. Readdition of HCO₃^- to these preparations restores the oscillatory pattern to higher flash numbers, indicating that HCO₃^- reduces the probability of “misses” in the photosystem II reaction center. The rate of the dark relaxation reaction S_n^′ → S_n+1 (where S refers to the oxidation state of the oxygen-evolving mechanism and n = 0, 1, or 2), after a photoact in the photosystem II reaction center, is retarded in HCO₃^--depleted chloroplasts compared to the rate for this reaction in depleted chloroplasts to which HCO₃^- has been resupplied. However, the final oxygen-evolving reaction after the accumulation of four positive charges appears to be independent of HCO₃^-. Bicarbonate has no effect on the dark deactivation of the higher oxidation states (S₂ and S₃) of the positive charge-accumulating system. We propose two alternate ways in which the kinetic model of oxygen evolution developed by Kok et al. [(1970) Photochem. Photobiol. 11, 457-475] can be extended to include the action of HCO₃^-.     

Electron nuclear double resonance evidence supporting a monomeric nature for P700 in spinach chloroplasts

Proton electron nuclear double resonance (ENDOR) spectra of P700⁺ in spinach chloroplasts and in photosystem I particles have been obtained and compared with the corresponding ENDOR spectrum of monomeric chlorophyl a⁺ (Chla⁺) cation radical. The hyperfine couplings for P700⁺ can be interpreted in terms of those expected for a monomer Chla⁺ radical. The reduction in α-carbon spin densities observed for the in vivo species when compared to the in vitro radical is attributed to differences in the composition of the ground-state orbital for the two systems. For P700⁺, a mixture of 75% D₀/25% D₁, in which D₀ and D₁ represent the ground-and first excited-state orbitals calculated by Petke et al. for Chla⁺ [Petke, J. D., Maggiora, G. M., Shipman, L. L. & Christoffersen, R. E. (1980) Photochem. Photobiol. 31, 243-257], gives good agreement between calculated and experimental spin-density reduction factors. Interaction of the pigment ion with its protein environment such as through ligation of the central Mg atom, hydrogen bonding to the 9-keto-carbonyl group, and electrostatic interactions with charged amino acid residues are proposed as factors responsible for the lowering in energy of the D₁ level in vivo. Combined with similar previous proposals for P680⁺ of photosystem II, the data suggest that both primary donor cation radicals of green plant photosynthesis can be viewed as monomeric Chla⁺ species in which the D₁ orbital makes a significant contribution to the spin-density distribution.     

Factors influencing ED care of young children at-risk for clinically important traumatic brain injury

Objectives

Care decisions for young children presenting to the emergency department (ED) with head injury are often challenging (e.g. whether to obtain neuroimaging). We sought to identify factors associated with acute management of children at-risk for clinically important traumatic brain injury (ciTBI) and describe symptom management.

Effect of hormone replacement therapy,tibolone and raloxifene on serum lipids,apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxifene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, climacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n=34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n=80), continuous combined 17β-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n=58), tibolone 2.5 mg (n=83) and raloxifene HCl 60 mg (n=50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA₁), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (?11.2%, ?11.9% and ?11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA₁ were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA₁, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, ?13.6%; and ApoA₁, ?9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (?13.2 to ?29.0%). In conclusion, each therapy regimen had a different effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

The changing face of gastroschisis and omphalocele in southeast Georgia

Objective: To document trends in the clinical characteristics of gastroschisis and omphalocele in southeast Georgia, USA, from 1994 to 2002.

Methods: All babies with an abdominal wall defect in a 19-county region were referred to one Perinatal Center for genetic counseling, level II ultrasound scans, pregnancy follow-up and delivery. Karyotyping was offered for omphalocele, advanced maternal age, family history predisposing to aneuploidy, and gastroschisis with an additional anomaly.

Results: There were 64 patients, 34 with gastroschisis and 30 with omphalocele. From 1994 to 2002, the birth prevalence of gastroschisis was 1:3600 and omphalocele 1:3400, but from 2000 to 2002, gastroschisis increased to 1:1667, while omphalocele increased to only 1:2709. Gender distribution was different: for gastroschisis the M:F ratio was 1:2.1; for omphalocele the ratio was 1.7:1. In the patients with omphalocele, 90% had an amniocentesis and 9/27 were aneuploid: five had trisomy 18, three had trisomy 13 and one had trisomy 21. Seventy-six per cent of the patients with omphalocele had associated anomalies, but only 17.6% of those with gastroschisis. Mothers whose babies had gastroschisis showed a trend to progressively younger age, while no such trend was observed among mothers whose babies had omphalocele.

Conclusion: The birth prevalence of abdominal wall defects in general is increasing, but more notably for gastroschisis. Maternal age continues to decrease for gastroschisis. In the study population, gender distribution showed a statistically significant variation between the defects.     

Mitochondrial aldehyde dehydrogenase (ALDH2) protects against streptozotocin-induced diabetic cardiomyopathy: role of GSK3β and mitochondrial function

Background

Mitochondrial aldehyde dehydrogenase (ALDH2) displays some promise in the protection against cardiovascular diseases although its role in diabetes has not been elucidated.

Methods

This study was designed to evaluate the impact of ALDH2 on streptozotocin-induced diabetic cardiomyopathy. Friendly virus B(FVB) and ALDH2 transgenic mice were treated with streptozotocin (intraperitoneal injection of 200 mg/kg) to induce diabetes.

Results

Echocardiographic evaluation revealed reduced fractional shortening, increased end-systolic and -diastolic diameter, and decreased wall thickness in streptozotocin-treated FVB mice. Streptozotocin led to a reduced respiratory exchange ratio; myocardial apoptosis and mitochondrial damage; cardiomyocyte contractile and intracellular Ca²⁺ defects, including depressed peak shortening and maximal velocity of shortening and relengthening; prolonged duration of shortening and relengthening; and dampened intracellular Ca²⁺ rise and clearance. Western blot analysis revealed disrupted phosphorylation of Akt, glycogen synthase kinase-3?? and Foxo3a (but not mammalian target of rapamycin), elevated PTEN phosphorylation and downregulated expression of mitochondrial proteins, peroxisome proliferator-activated receptor ?? coactivator 1?? and UCP-2. Intriguingly, ALDH2 attenuated or ablated streptozotocin-induced echocardiographic, mitochondrial, apoptotic and myocardial contractile and intracellular Ca²⁺ anomalies as well as changes in the phosphorylation of Akt, glycogen synthase kinase-3??, Foxo3a and phosphatase and tensin homologue on chromosome ten, despite persistent hyperglycemia and a low respiratory exchange ratio. In vitro data revealed that the ALDH2 activator Alda-1 and glycogen synthase kinase-3?? inhibition protected against high glucose-induced mitochondrial and mechanical anomalies, the effect of which was cancelled by mitochondrial uncoupling.

Conclusions

In summary, our data revealed that ALDH2 acted against diabetes-induced cardiac contractile and intracellular Ca²⁺ dysregulation, possibly through regulation of apoptosis, glycogen synthase kinase-3?? activation and mitochondrial function independent of the global metabolic profile.     

A physician's guide to helping patients with ADHD find success in the workplace

The impact of untreated adult attention-deficit/hyperactivity disorder (ADHD) in the workplace can be substantial, and employees with ADHD often confront frustration, employer disappointment, and low performance ratings. As a result, adults with ADHD may seek treatment from primary care providers to improve occupational performance. Previously considered a behavior disorder primarily affecting children and adolescents, ADHD in adulthood presents primarily as a cognitive disorder. Self-management deficits play a greater role in adult ADHD, particularly with respect to occupational and interpersonal functioning. Although specialized resources are available to assist adults with ADHD, many afflicted individuals may be unaware or unable to access them. Primary care providers who may be treating adults with ADHD are in a unique position to help them obtain the care and support needed to build appropriate skills and manage occupational issues. In this review, a literature search of the past 10 years was conducted to identify articles concerning ADHD and its impact on individuals in the workplace. The influence of ADHD on occupational functioning is discussed in the context of self-management impairments, diagnosis and assessment, and management strategies. With early and successful intervention, adults with ADHD may be able to become more aware of the impact of ADHD on work performance and achieve successful occupational experiences.     

Effects of formal and informal support structures on the motivation of Native American students in nursing

Native Americans have traditionally been underrepresented in nursing. The authors surveyed 19 undergraduate nursing students participating in a university sponsored Native American nursing student support program and examined which social support factors influenced the students' success. Using validated quantitative measures from social psychology, the authors found that overall perceived social support, as well as support from the university sponsored program, positively influenced Native American students' identification with nursing, their interest in nursing, their perception of the value of nursing, and their motivation to continue pursuing nursing as a career. Conversely, perceptions of unfairness due to racial bias within the major negatively affected students' perception of the value of nursing, as well as their motivation to pursue a nursing career.     

A comparative study of bacterial isolates from the urine samples of AIDS and non—AIDS patients in Benue,Nigeria

ObjectiveTo determine the common bacterial causes of urinary tract infection and their antibiotic susceptibility pattern in AIDS patients versus non-AIDS patients.MethodsOne thousand consecutive AIDS patients with signs and symptoms of AIDS and non-AIDS patients (served as control) each on admission were recruited into the study between January 2005 to January 2008, in Federal Medical Center, Makurdi. Urine samples were collected with sterile universal bottles and analysed with appropriate laboratory methods and antibiotic susceptibility test was carried out by disk diffusion technique in accordance with National Committee for Clinical Laboratory Standards (NCCLS, now CLSI) criteria. The results were analysed using SPSS 11.0 statistical software.ResultsUrine samples of AIDS patients with urinary infection had a more spectrum of micro-organisms including Candida organisms, Pseudomonas aeruginosa and Staphylococcus aureus. Ceftriaxone, Ceftazidime or Ciprofloxacin had a remarkably high anti-bacterial activity across the two study groups. A general resistance was recorded in ampicillin, tetracycline and co-trimoxazole. There was no significant difference in antibiotic susceptibility patterns between AIDS and non-AIDS patients (P>0.05).ConclusionsA reduction in unnecessary use of antibiotics as well as infection control should be encouraged in our health facilities.