Antimicrobial effects of XF drugs against Candida albicans and its biofilms.

Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C. albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.

Trapezium fracture: a common clinical mimic of scaphoid fracture.

PURPOSE: Fractures of the trapezium are rarely diagnosed on plain radiographs after acute wrist trauma. High-resolution cross-sectional imaging identifies fractures of the trapezium as the most common radiographically occult carpal bone fracture. We review the fracture frequency, mechanisms and patterns of trapezium fractures. METHODS: Cone beam CT was performed in patients with suspected radiographically occult radiocarpal fracture following acute injury. The frequency of carpal bone fractures was assessed and compared. RESULTS: Ninety-three radiographically occult wrist fractures were identified in 166 patients with acute trauma and negative radiographs. The trapezium was the most frequently fractured carpal bone, making up 20.4% of wrist fractures. Seventy-nine percent of trapezium fractures involved the volar ridge. The scaphoid was the clinically suspected fractured bone at initial assessment in 84% of patients with trapezium fractures. CONCLUSION: Fractures of the trapezium in acute wrist trauma are much more common than described in the literature. If initial radiographs are negative, a fracture of the trapezium is more likely to be present than one of the scaphoid, despite high levels of clinical suspicion for scaphoid injuries. Awareness of the types and mechanisms of trapezium fracture is important. Cross-sectional imaging should be considered in all cases of post-traumatic wrist pain with negative radiographs.

The role of laparoscopic sleeve gastrectomy as a treatment for morbid obesity; review of outcomes.

BACKGROUND: Global prevalence of obesity has soared. Where lifestyle and medical treatments have failed, laparoscopic sleeve gastrectomy (LSG) is increasingly regarded as a good surgical procedure for morbid obesity. Following the introduction of LSG, we assessed our surgical outcomes. METHODS: We reviewed a consecutive series of LSGs from January 2009 to January 2015. Our primary focus was to assess the success of this procedure on the percentage excess body weight loss (%EWL), Body Mass Index (BMI), hypertension and diabetes. Additionally, we evaluated the rate of procedure-related complications. RESULTS: There were 183 consecutive patients evaluated. Median age was 45 years (24-73). The majority were female (73.2 %, n = 134). At 1 year post-op, median %EWL was 57.6 %. There was an associated median reduction in BMI of 16 kg/m2 (0-33). At 2 years, median %EWL was sustained at 58.4 %. The median reduction in BMI was 16 kg/m2 (4-32). At 2-year post-op, 78.9 % of diabetic patients had their diabetic medications completely discontinued, while a further 15.8 % having their medication reduced. 34.6 % of hypertensive patients had their antihypertensives discontinued, with 50 % having medications reduced. There was no procedure related mortality. 3.3 % (n = 6) of patients had a confirmed staple-line leak. CONCLUSION: This study shows LSG is a safe and successful management strategy for morbid obesity. In addition to the direct effects of sustained weight loss, it highlights indirect effects that LSG has on obesity-related health issues, with substantial reduction in diabetic and anti-hypertensive medications. Our results reaffirm international studies of the beneficial effects of LSG on Type II diabetes and hypertension.

Effects of concentrate crude protein content on nutrient digestibility, energy utilization, and methane emissions in lactating dairy cows fed fresh-cut perennial grass.

Although many studies have investigated mitigation strategies for methane (CH4) output from dairy cows fed a wide variety of diets, research on the effects of concentrate crude protein (CP) content on CH4 emissions from dairy cows offered fresh grass is limited. The present study was designed to evaluate the effects of cow genotype and concentrate CP level on nutrient digestibility, energy utilization, and CH4 emissions in dairy cows offered fresh-grass diets. Twelve multiparous lactating dairy cows (6 Holstein and 6 Holstein × Swedish Red) were blocked into 3 groups for each breed and assigned to a low-, medium-, or high-CP concentrate diet [14.1, 16.1, and 18.1% CP on a dry matter (DM) basis, respectively], in a 3-period changeover study (25d per period). Total diets contained (DM basis) 32.8% concentrates and 67.2% perennial ryegrass, which was harvested daily. All measurements were undertaken during the final 6d of each period: digestibility measurements for 6d and calorimetric measurements in respiration chambers for 3d. Feed intake and milk production data were reported in a previous paper. We observed no significant interaction between concentrate CP level and cow genotype on any parameter. Concentrate CP level had no significant effect on any energy utilization parameter, except for urinary energy output, which was positively related to concentrate CP level. Similarly, concentrate CP content had no effect on CH4 emission (g/d), CH4 per kg feed intake, or nutrient digestibility. Cross breeding of Holstein cows significantly reduced gross energy, digestible energy, and metabolizable energy intake, heat production, and milk energy output. However, cow genotype had no significant effect on energy utilization efficiency or CH4 parameters. Furthermore, the present study yielded a value for gross energy lost as CH4 (5.6%) on fresh grass-based diets that was lower than the widely accepted value of 6.5%. The present findings indicate that reducing concentrate CP content from 18.1 to 14.1% may not be a successful way of alleviating CH4 emissions from lactating dairy cows offered good-quality fresh grass, but grazing cows could be offered a low-CP concentrate without compromising energy utilization efficiency. Further research is needed to investigate whether larger differences in dietary CP content may yield positive results.

Effects of crude protein level in concentrate supplements on animal performance and nitrogen utilization of lactating dairy cows fed fresh-cut perennial grass.

Nitrogen pollution of air and ground water from grazing cattle is of increasing concern. Although several studies have investigated mitigation strategies for nitrogen output from dairy cows fed conserved forages and concentrates, similar research on fresh-cut grass in addition to production parameters is limited. The current study, using 3dietary treatments and incorporating 2 genotypes, was designed to evaluate the effects of concentrate crude protein (CP) levels on animal production and nitrogen utilization efficiency (NUE) in lactating dairy cows. Twelve multiparous cows (6 Holstein and 6 Holstein × Swedish Red) were used in a changeover study with three 25-d periods and 3 diet treatments. Low, medium and high CP concentrate [14.1, 16.1, and 18.1%, respectively, dry matter (DM) basis] diets were fed at 32.8% DM intake combined with good-quality zero-grazed perennial ryegrass (18.2% CP, DM basis). Each period consisted of an adaptation phase (18d) housed as a single group, a 1-d adaptation phase in individual stalls, and a 6-d measurement phase with feed intake and feces, urine, and milk output recorded. We observed no significant interaction between cow genotype and concentrate CP level on any animal performance or NUE parameter. Total DM intake, milk yield and composition, and NUE were not affected by dietary treatment. However, increasing concentrate CP level increased (1) N intake by 42g/d and excretion in urine and manure by 38 and 40g/d, respectively, and (2) the ratio of urine N over manure N. Feeding high CP rather than low CP concentrate increased milk urea N (MUN) content by 3.6mg/dL and total MUN output by 1.08g/d. Crossbred cows had lower grass DM intake, total DM intake, total N intake, and energy-corrected milk yield. However, cow genotype had no significant effect on NUE or MUN parameters. Equations have been developed to predict urine N excretion using MUN output as a sole predictor or in combination with dietary CP level. The present study indicated that when grazing cows are fed good-quality pasture, feeding concentrates with a protein content as low as 14.1% may not negatively affect productivity. In addition, reducing concentrate CP concentration may be successful in reducing the urinary N excretion of lactating dairy cattle on pasture-based systems, but further research is needed to investigate the long-term effects of supplementary concentrate CP content on milk production.

Fracture of the scapular neck sustained in an arm wrestling match.

The sport of arm wrestling requires very little equipment, and can take place anywhere a flat surface is available. As such, undertrained participants often compete, with inevitable injury. Humeral fractures, and elbow injuries are well described, but scapular fractures have not previously been reported in the literature.

Health-related quality of life and functional outcomes following nerve transfers for traumatic upper brachial plexus injuries.

We report the patient-scored Health-Related Quality of Life (HRQoL) and functional outcomes of a cohort of 21 consecutive patients undergoing nerve transfer surgery for traumatic upper brachial plexus injuries. Outcomes were assessed using the British Medical Research Council power grading system, Short-Form 36, Disability of Arm, Shoulder and Hand questionnaire, and Pain Visual Analogue Scale (PVAS). The mean age of our cohort was 29.8 years (range 18-53 years), with a mean follow-up period of 42.9 months. At follow-up, elbow flexion ≥ M3 strength was achieved in 17/21 patients. Shoulder abduction ≥ M3 was achieved in 14/19 patients. External rotation ≥ M3 strength was achieved in 11/15 patients. Delayed surgical repair correlated negatively with HRQoL outcomes. Higher injury severity scores and smoking were associated with higher PVAS scores. These findings provide key prognostic information for patients and peripheral nerve surgeons embarking upon this intensive pathway to potential recovery.

An audit of hip fracture services in the Mater Hospital Dublin 2001 compared with 2006.

BACKGROUND: Evidence-based practice supports the provision of integrated geriatric multidisciplinary care for older people with hip fractures. AIMS: To show that introduction of orthogeriatric services resulted in improved care and better patient outcomes. METHODS: We compared two audits: a 2001 audit of 103 patients over the age of 65 years with hip fracture and a 2006 audit on 98 admissions using the same parameters. RESULTS: Inpatient mortality dropped from 20% to 8%. Discharge to home increased from 8% to 18% and to nursing home fell from 25% to 21%. Prescription of perioperative antibiotics, DVT prophylaxis and osteoporosis medications improved. There were no significant differences in age or sex but there were significantly higher levels of disability in the 2001 group. CONCLUSION: Following introduction of an orthogeriatric service, improvements in mortality and discharge destination occurred. This may have been influenced by higher proportions of disability among the 2001 cohort.

Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post-operative orthopaedic pain.

BACKGROUND: Propacetamol is an injectable pro-drug of paracetamol (acetaminophen) with analgesic and antipyretic activities, especially used in the post-operative period. The aim of this study was to assess the analgesic efficacy and safety of intravenous paracetamol, administered as propacetamol, in comparison with placebo and intramuscular diclofenac in patients with post-operative pain. METHODS: This was a randomized, double-blind, double-dummy study. One hundred and twenty patients with moderate to severe pain following total hip arthroplasty received either two administrations of propacetamol 2 g intravenously, 5 h apart (n = 40), one single administration of diclofenac 75 mg intramuscularly (n = 40) or placebo (n = 40). Efficacy measures were assessed before each drug administration, for the 5 h following each study treatment administration and for the total study duration of 10 h. Safety was assessed by reporting adverse events and changes in vital signs, electrocardiogram (ECG) and biochemical investigations before and 24 h after dosing. RESULTS: Both active treatments were effective and statistically superior to placebo over the whole study period, as indicated by the total pain relief score. No significant differences were found between propacetamol and diclofenac for any measures of analgesic activity. Only minor and common adverse events were reported, with no overall differences between the groups. CONCLUSION: Both active treatments were superior to placebo, and the overall efficacy of two intravenous infusions of propacetamol 2 g (equivalent to 1 g of paracetamol), 5 h apart, was not statistically different from that provided by a single intramuscular injection of diclofenac 75 mg over the first 5 h post-dose and over the total 10-h study period. The safety was good.

Carpal tunnel release using local anaesthetic and a forearm tourniquet.

Carpal tunnel release can be performed under general or local anaesthetic. However, many surgeons believe the upper arm tourniquet is not tolerated by the patient when awake. We use a forearm tourniquet for carpal tunnel decompression under local anaesthesia. The aim of this study is to assess patient tolerance of the technique. Between January 1st 1996 and December 31st 2000, 74 patients had carpal tunnel release performed using local anaesthesia. We sent a postal questionnaire to each, asking the patient to rate different aspects of the procedure. Fifty-eight patients replied (78% response). Forty-four of the respondents (76%) tolerated the tourniquet well, finding it to be 'no problem' or only 'mildly painful'. The same number reported they would prefer to have local anaesthesia again in the event of their requiring a similar operation on their hand. We believe carpal tunnel release using local anaesthetic and a forearm tourniquet is well tolerated by the patient.

Economic analysis of granulocyte colony stimulating factor as adjunct therapy for older patients with acute myelogenous leukemia (AML): estimates from a Southwest Oncology Group clinical trial.

Considerable morbidity, mortality, and economic costs result during remission induction therapy for elderly patients with acute myeloid leukemia (AML). In this study, the economic costs of adjunct granulocyte colony stimulating factor (G-CSF) are estimated for AML patients > 55 years of age who received induction chemotherapy on a recently completed Southwest Oncology Group study (SWOG). Clinical data were based on Phase III trial information from 207 AML patients who were randomized to receive either placebo or G-CSF post-induction therapy. Analyses were conducted using a decision analytic model with the primary source of clinical event probabilities based on in-hospital care with or without an active infection requiring intravenous antibiotics. Estimates of average daily costs of care with and without an infection were imputed from a previously reported economic model of a similar population. When compared to AML patients who received placebo, patients who received G-CSF had significantly fewer days on intravenous antibiotics (median 22 vs. 26, p = 0.05), whereas overall duration of hospitalization did not differ (median 29 days). The median cost per day with an active infection that required intravenous antibiotics was estimated to be $1742, whereas the median cost per day without an active infection was estimated to be $1467. Overall, costs were $49,693 for the placebo group and $50,593 for the G-CSF patients. G-CSF during induction chemotherapy for elderly patients with AML had some clinical benefits, but it did not reduce the duration of hospitalization, prolong survival, or reduce the overall cost of supportive care. Whether the benefits of G-CSF therapy justify its use in individual patients with acute leukemia for the present remains a matter of clinical judgment.

Hysterectomy in Veterans Affairs Medical Centers.

OBJECTIVE: To examine the indications and surgical morbidity for women veterans who underwent hysterectomies in Department of Veterans Affairs Medical Centers (VAs). METHODS: Data on hysterectomies performed in VAs from 1991 to 1997 were abstracted from a surgical quality improvement program. RESULTS: Records of 1722 women who had hysterectomies in VAs over 6 years were examined. Women were predominately white (62%) and their average age was 42.5 years. Operations included abdominal (74%), vaginal (22%), and laparoscopic-assisted (4%) methods. The most common indications for surgery included uterine leiomyomas (31%), abnormal uterine bleeding (14%), and endometriosis (11%). Indications differed by race (P <.01); nonwhite women were most likely to have surgery for leiomyoma (51%), whereas white women had hysterectomies for leiomyomas (19%), abnormal bleeding (15%), endometriosis (13%), and genital prolapse (11%). The mean postoperative stay was significantly longer for abdominal hysterectomies (4.51 days) than either vaginal or laparoscopic-assisted hysterectomies (2.92 and 2.21 days, respectively; P <.001). The overall complication rate within 30 days was 9%, and the most frequent complication was urinary tract infection (3.3%). CONCLUSION: Women who underwent hysterectomies in VAs had low complication rates, comparable to hysterectomy complication rates in the United States generally.

Predicting non-elective hospital readmissions: a multi-site study. Department of Veterans Affairs Cooperative Study Group on Primary Care and Readmissions.

OBJECTIVE: To determine clinical and patient-centered factors predicting non-elective hospital readmissions. DESIGN: Secondary analysis from a randomized clinical trial. CLINICAL SETTING: Nine VA medical centers. PARTICIPANTS: Patients discharged from the medical service with diabetes mellitus, congestive heart failure, and/or chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASUREMENT: Non-elective readmission within 90 days. RESULTS: Of 1378 patients discharged, 23.3% were readmitted. After controlling for hospital and intervention status, risk of readmission was increased if the patient had more hospitalizations and emergency room visits in the prior 6 months, higher blood urea nitrogen, lower mental health function, a diagnosis of COPD, and increased satisfaction with access to emergency care assessed on the index hospitalization. CONCLUSIONS: Both clinical and patient-centered factors identifiable at discharge are related to non-elective readmission. These factors identify high-risk patients and provide guidance for future interventions. The relationship of patient satisfaction measures to readmission deserves further study.

Database and informatics support for QUERI: current systems and future needs. Quality Enhancement Research Initiative.

OBJECTIVES: Our primary objective is to provide an overview of database and informatics support for the Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI). METHODS: We discuss the role of information technology resources in the QUERI process. We also review current VA information systems and specific databases in terms of strengths and weaknesses for addressing the QUERI goals. A synthesis of the issues and strategies for addressing specific data needs are presented by use of examples from 2 of the QUERI disease modules: Diabetes Mellitus and Human Immunodeficiency Virus. Finally, we discuss issues that need to be considered during development of new information systems to address the needs of clinical quality-improvement efforts. CONCLUSIONS: Quality enhancement in VA health care requires coordination and careful planning among clinical, administrative, research, policy, and information technology leaders to ensure that key clinical process and outcome measures are reliably collected in the VA information systems. As the QUERI progresses, data needs will probably shift from addressing data gaps to developing approaches for feedback and evaluation. Continued and enhanced cooperation among all VHA business processes is vital to the success of the QUERI.

Research as a key to promoting and sustaining innovative practice.

During the past decade, we have witnessed increasing emphasis on the integration of research and clinical care with the evolution of evidence-based practice and best practices. The principles underlying evidence-based medicine and best practices are fundamental to understanding the interdependence of research and innovation. These principles helped guide the US Department of Veterans Affairs (VA) Nursing Innovations Task Force to review and critique programs at VA health care facilities across the United States. This article reviews how the task force applied concepts and principles of evidence-based practice to identify innovative practices at VA health care facilities. Also described are task force recommendations to foster innovative practice through increased nursing research capacity, and strategies are suggested for applying these principles in other health care settings.

Giant distal humeral geode.

We describe the imaging features of a giant geode of the distal humerus in a patient with rheumatoid arthritis, which presented initially as a pathological fracture. The value of magnetic resonance imaging in establishing this diagnosis is emphasized.

An investigation into the role of oxygen free radical scavengers in preventing polymethylmethacrylate-induced necrosis in an osteoblast cell culture.

This study examined the effect of polymethylmethacrylate (PMMA) on osteocytic necrosis and the role of free radical scavengers in minimizing this damage. Bovine osteoblast cells with a characteristic phenotype were seeded at a density of 4x10(4) cells/cm2 and cultured in a DMEM supplemented with 10% fetal calf serum. A transwell insert with 2 cc of PMMA was suspended above the culture, and a time log response curve was established following elusion of free radicals around the osteoblast media. Chemiluminescence was used to determine quantitative free radical release. Using a Student's two-tailed t test there was a significant difference in the amount of hydroxyl radical released at 1-6 hours compared with controls (P=.028). Using histologic markers, there was a significant correlation between the use of PMMA and osteoblast cell necrosis. Transwell plates were coated with varying concentrations of mannitol, a known hydroxyl radical scavenger. A log dose response curve was established. There was a clear statistical association between a 10% mannitol solution and a reduction in the free radical release from PMMA (P=.03). Similarly, using Trypan blue histologic staining, there was a significant reduction in PMMA-induced cell necrosis when 10% mannitol was used as a scavenger (P=.01). A Rockwell superficial hardness test was used to determine whether mannitol had any effect on the surface hardness of the polymer. No statistical difference could be found between those treated with mannitol and controls at a depth of up to 1 mm. These results demonstrate hydroxyl radical is released from the polymerization reaction of PMMA. These radicals cause cell death in an osteoblast culture medium. This has been addressed using a 10% mannitol solution, which reduced cell necrosis.