bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemodynamic goal-directed therapy and postoperative infections: earlier is better. a systematic review and meta-analysis
Authors: Dalfino Lidia , Giglio Maria T , Puntillo Filomena , Marucci Massimo , Brienza Nicola
Published: June 2011

Introduction

Infectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates.

Methods

We performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection.

Results

Twenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001).

Conclusions

Flow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.
The Benefits of Aggregate Performance Metrics in the Presence of Career Concerns
Authors: Arya Anil , Mittendorf Brian
Published: June 2011

This paper considers the desirability of aggregate performance measures in light of the fact that many individuals' performance incentives are driven by a desire to shape external perceptions (and thus future pay). In contrast to the case of explicit incentive contracts, we find that when individuals' actions are driven by career incentives, an aggregate measure (e.g., group or team output) can sometimes alleviate moral hazard concerns and improve efficiency. Aggregation intermingles performance measures that may be differentially affected by skill and effort of many agents. When such entanglement increases the prospect that the external market will attribute an employee's effort-driven contribution to transferable skills, the employee exerts higher effort as a means of posturing to the market. The incentive benefit of aggregation is weighed against the incentive cost because of information loss. Information loss from aggregation can reduce the market's reliance on the measure and thus diminish agents' desire to undertake effort to influence the measure.

This paper was accepted by Stefan Reichelstein, accounting.
Arthroscopy of the hip in patients following joint replacement
Authors: Bajwa A. S. , Villar R. N.
Published: June 2011

Arthroscopy of the native hip is an established diagnostic and therapeutic procedure. Its application in the symptomatic replaced hip is still being explored. We describe the use of arthroscopy of the hip in 24 symptomatic patients following total hip replacement, resurfacing arthroplasty of the hip and partial resurfacing (study group), and compared it with arthroscopy of the native hip in 24 patients (control group). A diagnosis was made or confirmed at arthroscopy in 23 of the study group and a therapeutic arthroscopic intervention resulted in relief of symptoms in ten of these. In a further seven patients it led to revision hip replacement. In contrast, arthroscopy in the control group was diagnostic in all 24 patients and the resulting arthroscopic therapeutic intervention provided symptomatic relief in 21.

The mean operative time in the study group (59.7 minutes (35 to 93)) was less than in the control group (71 minutes (40 to 100), p = 0.04) but the arthroscopic approach was more difficult in the arthroplasty group. We suggest that arthroscopy has a role in the management of patients with a symptomatic arthroplasty when other investigations have failed to provide a diagnosis.
Soft-tissue changes in hip abductor muscles and tendons after total hip replacement
Authors: Bremer A. K. , Kalberer F. , Pfirrmann C. W. A. , Dora C.
Published: June 2011

The direct anterior approach in total hip replacement anatomically offers the chance to minimise soft-tissue trauma because an intermuscular and internervous plane is explored. This motivated us to abandon our previously used transgluteal approach and to adopt the direct anterior approach for total hip replacement. Using MRI, we performed a retrospective comparative study of the direct anterior approach with the transgluteal approach. There were 25 patients in each group. At one year post-operatively all the patients underwent MRI of their replaced hips. A radiologist graded the changes in the soft-tissue signals in the abductor muscles. The groups were similar in terms of age, gender, body mass index, complexity of the reconstruction and absence of symptoms.

Detachment of the abductor insertion, partial tears and tendonitis of gluteus medius and minimus, the presence of peri-trochanteric bursal fluid and fatty atrophy of gluteus medius and minimus were significantly less pronounced and less frequent when the direct anterior approach was used. There was no significant difference in the findings regarding tensor fascia lata between the two approaches.

We conclude that use of the direct anterior approach results in a better soft-tissue response as assessed by MRI after total hip replacement. However, the impact on outcome needs to be evaluated further.
The biomechanical performance of locking plate fixation with intramedullary fibular strut graft augmentation in the treatment of unstable fractures of the proximal humerus
Authors: Bae J.-H. , Oh J.-K. , Chon C.-S. , Oh C.-W. , Hwang J.-H. , Yoon Y.-C.
Published: June 2011

We evaluated the biomechanical properties of two different methods of fixation for unstable fractures of the proximal humerus. Biomechanical testing of the two groups, locking plate alone (LP), and locking plate with a fibular strut graft (LPSG), was performed using seven pairs of human cadaveric humeri. Cyclical loads between 10 N and 80 N at 5 Hz were applied for 1 000 000 cycles. Immediately after cycling, an increasing axial load was applied at a rate of displacement of 5 mm/min. The displacement of the construct, maximum failure load, stiffness and mode of failure were compared.

The displacement was significantly less in the LPSG group than in the LP group (p = 0.031). All maximum failure loads and measures of stiffness in the LPSG group were significantly higher than those in the LP group (p = 0.024 and p = 0.035, respectively). In the LP group, varus collapse and plate bending were seen. In the LPSG group, the humeral head cut out and the fibular strut grafts fractured. No broken plates or screws were seen in either group.

We conclude that strut graft augmentation significantly increases both the maximum failure load and the initial stiffness of this construct compared with a locking plate alone.
Scheuermann’s kyphosis; current controversies
Authors: Tsirikos A. I. , Jain A. K.
Published: June 2011

This review of the literature presents the current understanding of Scheuermann’s kyphosis and investigates the controversies concerning conservative and surgical treatment. There is considerable debate regarding the pathogenesis, natural history and treatment of this condition. A benign prognosis with settling of symptoms and stabilisation of the deformity at skeletal maturity is expected in most patients. Observation and programmes of exercise are appropriate for mild, flexible, non-progressive deformities. Bracing is indicated for a moderate deformity which spans several levels and retains flexibility in motivated patients who have significant remaining spinal growth.

The loss of some correction after the completion of bracing with recurrent anterior vertebral wedging has been reported in approximately one-third of patients. Surgical correction with instrumented spinal fusion is indicated for a severe kyphosis which carries a risk of progression beyond the end of growth causing cosmetic deformity, back pain and neurological complications. There is no consensus on the effectiveness of different techniques and types of instrumentation. Techniques include posterior-only and combined anteroposterior spinal fusion with or without posterior osteotomies across the apex of the deformity. Current instrumented techniques include hybrid and all-pedicle screw constructs.
The Andersson lesion in ankylosing spondylitis
Authors: Park Y.-S. , Kim J.-H. , Ryu J.-A. , Kim T.-H.
Published: June 2011

A number of causes have been advanced to explain the destructive discovertebral (Andersson) lesions that occur in ankylosing spondylitis, and various treatments have been proposed, depending on the presumed cause. The purpose of this study was to identify the causes of these lesions by defining their clinical and radiological characteristics.

We retrospectively reviewed 622 patients with ankylosing spondylitis. In all, 33 patients (5.3%) had these lesions, affecting 100 spinal segments. Inflammatory lesions were found in 91 segments of 24 patients (3.9%) and traumatic lesions in nine segments of nine patients (1.4%). The inflammatory lesions were associated with recent-onset disease; a low modified Stoke ankylosing spondylitis spine score (mSASSS) due to incomplete bony ankylosis between vertebral bodies; multiple lesions; inflammatory changes on MRI; reversal of the inflammatory changes and central bony ankylosis at follow-up; and a good response to anti-inflammatory drugs. Traumatic lesions were associated with prolonged disease duration; a high mSASSS due to complete bony ankylosis between vertebral bodies; a previous history of trauma; single lesions; nonunion of fractures of the posterior column; acute kyphoscoliotic deformity with the lesion at the apex; instability, and the need for operative treatment due to that instability.

It is essential to distinguish between inflammatory and traumatic Andersson lesions, as the former respond to medical treatment whereas the latter require surgery.
Neuritis ossificans of the tibial, common peroneal and lateral sural cutaneous nerves
Authors: Katz L. D. , Lindskog D. , Eisen R.
Published: June 2011

We describe a 23-year-old woman with neuritis ossificans involving the tibial, common peroneal and lateral sural nerves. She presented with chronic debilitating posterior knee pain. An MRI scan showed masses in these nerves, biopsy of which revealed a histological diagnosis of neuritis ossificans. Treatment with OxyContin and Neurotin for two years resulted in resolution of symptoms. Follow-up MRI demonstrated a resolution of two of the three masses. There was a persistent area of ossification without associated oedema in the common peroneal nerve. Neuritis ossificans has the histological appearance of myositis ossificans and follows a similar clinical course. The success of conservative treatment in this case suggests that the potential complications of surgical excision can be avoided.
Is a fracture of the transverse process of L5 a predictor of pelvic fracture instability?
Authors: Starks I. , Frost A. , Wall P. , Lim J.
Published: June 2011

In the management of a pelvic fracture prompt recognition of an unstable fracture pattern is important in reducing mortality and morbidity. It is believed that a fracture of the transverse process of L5 is a predictor of pelvic fracture instability. However, there is little evidence in the literature to support this view. The aim of this study was to determine whether a fracture of the transverse process of L5 is a reliable predictor of pelvic fracture instability.

We reviewed our hospital trauma database and identified 80 patients who sustained a pelvic fracture between 2006 and 2010. There were 32 women and 48 men with a mean age of 40 years (10 to 96). Most patients were injured in a road traffic accident or as a result of a fall from a height. A total of 41 patients (51%) had associated injuries. The pelvic fractures were categorised according to the Burgess and Young classification. There were 45 stable and 35 unstable fractures. An associated fracture of the transverse process of L5 was present in 17 patients; 14 (40%) of whom had an unstable fracture pattern. The odds ratio for an unstable fracture of the pelvis in the presence of a fracture of the transverse process of L5 was 9.3 and the relative risk was 2.5.

A fracture of the transverse process of L5 in the presence of a pelvic fracture is associated with an increased risk of instability of the pelvic fracture. Its presence should alert the attending staff to this possibility.
Analysis-By-Synthesis of Timbre, Timing, and Dynamics in Expressive Clarinet Performance
Authors: Barthet Mathieu , Depalle Philippe , Kronland-Martinet Richard , Ystad Sølvi
Published: June 2011

In a Previous Study, Mechanical and Expressive clarinet performances of Bach's Suite No. II and Mozart's Quintet for Clarinet and Strings were analyzed to determine whether some acoustical correlates of timbre (e.g., spectral centroid), timing (intertone onset interval), and dynamics (root mean square envelope) showed significant differences depending on the expressive intention of the performer. In the present companion study, we investigate the effects of these acoustical parameters on listeners' preferences. An analysis-by-synthesis approach was used to transform previously recorded clarinet performances by reducing the expressive deviations from the spectral centroid, the intertone onset interval and the acoustical energy. Twenty skilled musicians were asked to select which version they preferred in a paired comparison task. The results of statistical analyses showed that the removal of the spectral centroid variations resulted in the greatest loss of musical preference.
A Comparison of Rhythm in English Dialects and Music
Authors: McGowan Rebecca W. , Levitt Andrea G.
Published: June 2011

Informal Observations have Often been Made That a country's language is reflected in its instrumental music. Limited research exists studying similarities between the rhythmic characteristics of French music and language on the one hand and British music and language on the other. Our research compares the rhythmic characteristics of the music and English dialects of the Shetland Islands in Scotland, County Donegal in Ireland, and the state of Kentucky, examining spontaneous speech and unscored musical recordings from the same people. We found that rhythmic characteristics are correlated in the speech and music in each dialect area.
The Tonic as Triad: Key Profiles as Pitch Salience Profiles of Tonic Triads
Authors: Parncutt Richard
Published: June 2011

Major and minor triads emerged in western music in the 13th to 15th centuries. From the 15th to the 17th centuries, they increasingly appeared as final sonorities. In the 17th century, music-theoretical concepts of sonority, root, and inversion emerged. I propose that since then, the primary perceptual reference in tonal music has been the tonic triad sonority (not the tonic tone or chroma) in an experiential (not physical or notational) representation. This thesis is consistent with the correlation between the key profiles of Krumhansl and Kessler (1982; here called chroma stability profiles) and the chroma salience profiles of tonic triads (after Parncutt, 1988). Chroma stability profiles also correlate with chroma prevalence profiles (of notes in the score), suggesting an implication-realization relationship between the chroma prevalence profile of a passage and the chroma salience profile of its tonic triad. Convergent evidence from psychoacoustics, music psychology, the history of composition, and the history of music theory suggests that the chroma salience profile of the tonic triad guided the historical emergence of major-minor tonality and continues to influence its perception today.
Probing the Minor Tonal Hierarchy
Authors: Vuvan Dominique T. , Prince Jon B. , Schmuckler Mark A.
Published: June 2011

one facet of tonality perception that has been fairly understudied in the years since Krumhansl and colleagues' groundbreaking work on tonality (Krumhansl & Kessler, 1982; Krumhansl & Shepard, 1979) is the music theoretical notion that the minor scale can have one of three distinct forms: natural, harmonic, or melodic. The experiment reported here fills this gap by testing if listeners form distinct mental representations of the minor tonal hierarchy based on the three forms of the minor scale. Listeners heard a musical context (a scale or a sequence of chords) consisting of one of the three minor types (natural, harmonic, or melodic) and rated a probe tone according to how well it belonged with the preceding context. Listeners' probe tone ratings corresponded well to the minor type that had been heard in the preceding context, regardless of whether the context was scalar or chordal. These data expand psychological research on the perception of tonality, and provide a convenient reference point for researchers investigating the mental representation of Western musical structure.
A selective estrogen receptor α agonist ameliorates hepatic steatosis in the male aromatase knockout mouse
Authors: Chow Jenny D Y , Jones Margaret E E , Prelle Katja , Simpson Evan R , Boon Wah Chin
Published: June 2011

Male aromatase knockout mice (ArKO; an estrogen-deficient model) present with male-specific hepatic steatosis that is reversible upon 17β-estradiol replacement. This study aims to elucidate which estrogen receptor (ER) subtype, ERα or ERβ, is involved in the regulation of triglyceride (TG) homeostasis in the liver. Nine-month-old male ArKO mice were treated with vehicle, ERα- or ERβ-specific agonists via s.c. injection, daily for 6 weeks. Male ArKO mice treated with ERα agonist had normal liver histology and TG contents compared with vehicle-treated ArKO; omental (gonadal) and infra-renal (visceral) fat pad weights were normalized to those of vehicle-treated wild-type (WT). In contrast, ERβ agonist treatment did not result in the similar reversal of these ArKO phenotypes. In vehicle-treated ArKO mice, hepatic transcript expression of fatty acid synthase (Fasn) and stearoyl-coenzyme A desaturase 1 (key enzymes inde novoFA synthesis) were significantly elevated compared with vehicle-treated WT, but onlyFasnexpression was lowered to WT level after ERα agonist treatment. There were no significant changes in the transcript levels of carnitine palmitoyl transferase 1 (required for transfer of FA residues into the mitochondria for β-oxidation) and sterol regulatory element-binding factor 1c (the upstream regulator ofde novoFA synthesis). We also confirmed by RT-PCR that only ERα is expressed in the mouse liver. There were no changes in hepatic androgen receptor transcript level across all treatment groups. Our data suggest that estrogens act via ERα to regulate TG homeostasis in the ArKO liver. Since the liver, adipose tissue and arcuate nucleus express mainly ERα, estrogens could regulate hepatic functions via peripheral and central pathways.
A Flexible Estimating Equations Approach for Mapping Function-Valued Traits
Authors: Xiong Hao , Goulding Evan H , Carlson Elaine J , Tecott Laurence H , McCulloch Charles E , Sen Śaunak
Published: June 2011

In genetic studies, many interesting traits, including growth curves and skeletal shape, have temporal or spatial structure. They are better treated as curves or function-valued traits. Identification of genetic loci contributing to such traits is facilitated by specialized methods that explicitly address the function-valued nature of the data. Current methods for mapping function-valued traits are mostly likelihood-based, requiring specification of the distribution and error structure. However, such specification is difficult or impractical in many scenarios. We propose a general functional regression approach based on estimating equations that is robust to misspecification of the covariance structure. Estimation is based on a two-step least-squares algorithm, which is fast and applicable even when the number of time points exceeds the number of samples. It is also flexible due to a general linear functional model; changing the number of covariates does not necessitate a new set of formulas and programs. In addition, many meaningful extensions are straightforward. For example, we can accommodate incomplete genotype data, and the algorithm can be trivially parallelized. The framework is an attractive alternative to likelihood-based methods when the covariance structure of the data is not known. It provides a good compromise between model simplicity, statistical efficiency, and computational speed. We illustrate our method and its advantages using circadian mouse behavioral data.
The Joint Effects of Background Selection and Genetic Recombination on Local Gene Genealogies
Authors: Zeng Kai , Charlesworth Brian
Published: June 2011

Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data.
Role of plasmapheresis in immunological kidney diseases. Experience from 1050 completed plasmapheresis treatment sessions
Authors: Haris Ágnes , Arányi József , Braunitzer Henrik , Kálmán Éva , Merán Zoltán , Soltész Mariann , Polner Kálmán
Published: June 2011

Plasmapheresis is an effective treatment modality in several immunological kidney diseases. It is also indicated in certain neurological and hematological abnormalities, and some other diseases. Aims: In this study the indications and outcomes of the plasma exchange treatments performed in the Plasmapheresis Unit of the authors during the last 12 years are summarized, and the findings are compared to those published in the literature. The procedure, mechanisms of action and adverse effects are also briefly discussed. Methods: Between 1999 and 2010 authors completed 1050 plasma exchanges in 195 patients with an average 5.4 (1-20) treatments/person. In the 78 males and 117 females (age 57±16 years) the indications were as follows: 47% anti-cytoplasmic antibody-associated vasculitis, 4% anti-glomerular basement membrane disease, 3% rapidly progressing immunocomplex glomerulonephritis, 11% severe complications of systemic lupus erythematosus, 1% treatment resistant focal segmental glomerular sclerosis, 5% hemolytic uremic syndrome, 13% complications of multiple myeloma, 4% HELLP syndrome, 10% neurological diseases, and 2% other abnormalities. Results: Plasmapheresis, completed as part of combined immunosuppressive treatment, resulted in remarkable improvements in patients with anti-cytoplasmic antibody-associated vasculitis. Out of the 91 patients, 54 needed urgent dialysis on admission, and renal replacement therapy could be discontinued in 44% of them. Renal functions in those patients who did not need dialysis also improved significantly, and pulmonary hemorrhage ceased in all affected subjects. Survival of the patients with anti-glomerular basement membrane diseases was 100%. The treatment significantly improved the renal function in rapidly progressive lupus nephritis, and all the 5 cases of lupus cerebritis were successfully cured. The results showed less effectiveness in therapy resistant focal segmental glomerular sclerosis and in rapidly progressing immunocomplex glomerulonephritis. Plasmapheresis proved to be very efficient in cases with the primary hemolytic uremic syndrome, and each patient with HELLP syndrome recovered completely. The outcome of those with multiple myeloma was less favorable, although hyperviscosity was rapidly and effectively decreased by the plasmapheresis. The treatment improved the conditions of almost all patients with neurological diseases. Discussion: According to these findings plasmapheresis treatment, introduced by proper indications, effectively improves the outcomes of several diseases. Early diagnosis and immediate introduction of the plasmapheresis are very important – in conjunction with the appropriate therapy of the underlying diseases. Orv. Hetil., 2011, 152, 1110–1119.
Incidence of Clostridium difficile Infections in Patients Receiving Antimicrobial and Acid‐Suppression Therapy
Authors: King Rachel N. , Lager Stephanie L.
Published: June 2011

Study Objectives. To determine the incidence of Clostridium difficile infection (CDI) at one community hospital by identifying patients with stool samples positive for C. difficile toxin A or B, and to compare the incidence with a 2008 national estimate; and to determine which patient characteristics and concomitant antimicrobial and acid‐suppression drugs are risk factors for the development of CDI.

Design. Retrospective, single‐center, medical record review.

Setting. 350‐bed community hospital.

Patients. A total of 11,010 admissions between January 1, 2009, and December 31, 2009; 115 of these patients had stool samples positive for C. difficile toxin A or B.

Measurements and Main Results. All C. difficile toxin A and B enzyme immunoassay tests were performed by a central laboratory. The incidence of CDI was 10.4 cases/1000 patient admissions, which was significantly lower than the overall incidence reported in a 2008 national survey of 13.1 CDI cases/1000 patient admissions (p=0.021). Demographic and clinical data of the patients with CDI were collected by using electronic medical records. Patients were more likely to be elderly and female, and to have developed CDI during hospitalization. Of the 115 patients, 95 (82.6%) received acid‐suppression therapy and 91 (79.1%) received antimicrobials. Of the patients receiving acid‐suppression therapy, 72 (75.8%) received a proton pump inhibitor during their hospitalization, and 49 (51.6%) received both a proton pump inhibitor and an antibiotic. The most frequently used antibiotics in this population were fluoroquinolones, cephalosporins, and carbapenems, with a significantly larger proportion of patients who received carbapenems developing CDI compared with the other classes of antibiotics (p<0.05 for both comparisons). Patients receiving antimicrobial and acid‐suppression therapy were more likely to develop CDI than those who did not receive these drugs.

Conclusion. The incidence of CDI in 2009 at one community hospital was significantly lower than a 2008 national estimate. Antimicrobial and acid‐suppression therapies—in particular, combinations of fluoroquinolones, cephalosporins, carbapenems, and proton pump inhibitors—were found to be risk factors for the development of CDIs in hospitalized patients.
Dosing and Monitoring of Low‐Molecular‐Weight Heparin in High‐Risk Pregnancy: Single‐Center Experience
Authors: Shapiro Nancy L. , Kominiarek Michelle A. , Nutescu Edith A. , Chevalier Aimee B. , Hibbard Judith U.
Published: June 2011

Study Objective. To evaluate dosing requirements and monitoring patterns of low‐molecular‐weight heparin (LMWH) when usedinhigh‐risk pregnancy.

Design. Retrospective, observational, cohort study.

Setting. University‐affiliated medical center.

Patients. Forty‐nine women treated with LMWH between 2001 and 2005 for either prophylaxis or treatment of venous thromboembolism during pregnancy and monitored with antifactor Xa activity.

Measurements and Main Results. Data were obtained on 53 pregnancies in the 49 women. The primary outcome was change in dosing requirements of LMWH throughout pregnancy as determined by the corresponding antifactor Xa activity peak levels. Mean starting doses of twice‐daily enoxaparin and doses most proximate to delivery were 39.2 mg (range 30–60 mg) and 55.0 mg (range 30–100 mg, p=0.06), respectively, for the prophylaxis group and 83.0 mg (range 30–180 mg) and 85.7 mg (range 30–160 mg, p=0.41), respectively, for the therapeutic group. Weight‐based mean starting doses and doses most proximate to delivery were 0.46 and 0.62 mg/kg (p=0.03), respectively, for the prophylaxis group and 0.90 and 0.87 mg/kg (p=0.29), respectively, for the therapeutic group. Dose changes were required in 9 (69%) of 13 pregnancies and 21 (55%) of 38 pregnancies (data from two of the 40 pregnancies were excluded—one in a patient receiving dalteparin, and one in a patient with mitral valve replacement who had higher antifactor Xa goals) in the prophylaxis and therapeutic groups, respectively, to achieve target antifactor Xa activity. The weight‐based prophylactic dose was consistently 0.6 mg/kg in all three trimesters, achieving a mean ± SD target antifactor Xa activity of 0.39 ± 0.18 units/ml, whereas the therapeutic dose was 0.9 mg/kg to maintain antifactor Xa activity of 0.71 ± 0.22 units/ml.

Conclusion. Dose changes for LMWH throughout pregnancy as guided by antifactor Xa activity were common. A significant increase in the LMWH dose requirements in the prophylactic group suggests that more frequent monitoring of antifactor Xa activity may be appropriate in pregnant patients to maintain target anticoagulant levels.
Safety and Effectiveness of U‐500 Insulin Therapy in Patients with Insulin‐Resistant Type 2 Diabetes Mellitus
Authors: Quinn Suzanne L. , Lansang M. Cecilia , Mina Deanna
Published: June 2011

Study Objective. To assess the safety and effectiveness of highly concentrated U‐500 regular insulin in patients with insulin‐resistant type 2 diabetes mellitus who were switched from U‐100 insulin.

Design. Retrospective cohort study.

Setting. Outpatient diabetes management clinic.

Patients. Twenty‐one adults with poorly controlled type 2 diabetes and insulin resistance who were referred to the clinic between July 1, 2007, and June 30, 2008, and whose therapy was changed from large doses of U‐100 insulin to U‐500 insulin.

Measurements and Main Results. Demographic and clinical data were collected through a computerized medical record system. Insulin resistance was defined as a requirement of more than 200 units/day of insulin and more than 100 units/injection. The primary outcome was the change in hemoglobin A1c (A1C) after switching from any type of U‐100 insulin to stabilization with U‐500 highly concentrated regular insulin. Secondary outcomes were the changes in number of daily insulin injections, daily insulin dose, and body weight. With use of U‐500 insulin, patients were able to achieve an average reduction in A1C of 1.7% (p<0.001). The mean number of daily injections decreased from 4.3 with U‐100 insulin to 2.7 after using U‐500 insulin (p<0.001), but changes in body weight after the change in insulin were not statistically significant (279.8 vs 279.2 lbs, p=0.429). No patient discontinued U‐500 insulin during the study, and none experienced hypoglycemia severe enough to require the assistance of another individual.

Conclusion. In patients with insulin‐resistant diabetes who have requirements of more than 200 units/day or 100 units/injection, use of U‐500 regular insulin provided the same or better glucose control compared with U‐100 insulin, with fewer daily injections and reduced injection volume. Although this drug represents an excellent treatment option, its safe use requires an experienced physician, a motivated and cooperative patient, and a dynamic diabetes management team.
Tenets for Developing Quality Measures for Ambulatory Clinical Pharmacy Services
Authors: McBane Sarah , Trewet CoraLynn B. , Havican S. Nadra , Kiser Katie , Klingel Christine , Riche Daniel M. , Sease Julie M. , Nau David P. , Zillich Alan J.
Published: June 2011

During the past several years, the emphasis on quality in health care has been evolving. Alongside this evolution of change has been the advancement of clinical pharmacy services in ambulatory care settings. Although they share importance, both health care quality and ambulatory clinical pharmacy services have progressed and moved in their own directions. Nevertheless, in today's evolving health care landscape, collaboration among providers, including pharmacists, must occur to enhance quality. Pharmacy services must improve quality to be a sustainable health care service. This White Paper provides a rationale and structure that unite health care quality and ambulatory clinical pharmacy services. By applying national principles of quality measurement, this paper proposes five tenets to consider when developing measures for clinical pharmacy services in the ambulatory care setting: comprehensive, accountable, scientifically sound, feasible, and usable. Definitions of each tenet are presented. This paper uses exemplary literature on ambulatory clinical pharmacy services including diabetes mellitus, dyslipidemia, chronic lung disease, hypertension, anticoagulation, and heart failure to provide a context for the tenets and a discussion of their use. This paper also describes issues pertaining to health care quality and related costs using similar exemplary literature. Finally, a discussion is presented on both the opportunities and the challenges of measuring quality for ambulatory clinical pharmacy services. Issues related to the tenets, including shared accountability for health care quality, availability of comprehensive data to assess quality outcomes, feasibility of collecting and reporting quality, and the need for additional rigorous scientific evaluation of ambulatory clinical pharmacy services, are described.
Current Targeted Therapies in Breast Cancer: Clinical Applications in the Elderly Woman
Authors: Spano Jean-Philippe , Falandry Claire , Chaibi Pascal , Freyer Gilles
Published: June 2011

Learning Objectives

After completing this course, the reader will be able to: Include geriatric assessment into oncologic practice to describe patients and to evaluate the real benefit/risk ratio of any adjuvant treatment.Describe the actual risk of association of erythropoiesis-stimulating agents with bevacizumab.

This article is available for continuing medical education credit at CME.TheOncologist.com

The incidence of breast cancer is two to three times higher in women aged ≥65 years than in the whole population, whereas their mortality rate is threefold to fourfold higher. Targeted therapies allow significantly longer disease-free survival times. Nevertheless, in an elderly population, these treatments need to be prescribed with caution. This paper reviews the treatments of breast cancer in the elderly, and the issues of targeted therapies and their toxicities.

Patients with human epidermal growth factor receptor (HER)-2+ breast cancer benefit from trastuzumab; although cardiotoxic effects are observed in <5% of patients when given alone, they affect ∼25% of patients when combined with anthracyclines. Bevacizumab leads to a longer progression-free survival time and lower risk for progression in patients with metastatic breast cancer when added to paclitaxel or docetaxel. Although generally well tolerated, it is associated with a higher risk for arterial thromboembolism and hypertension. Lapatinib is approved for the treatment of advanced or metastatic breast cancer in patients not responding to trastuzumab, combined with capecitabine chemotherapy. The most frequent side effects concern the gastrointestinal system and dermatologic symptoms.

The life expectancy of breast cancer patients should be taken into account to determine the appropriateness of treatments. The quality of life of elderly cancer patients must be assessed with an appropriate tool. Older patients exhibit greater vulnerability, suggesting identification and exclusion of patients at high cardiac risk.

Future recommendations for the treatment of elderly women with breast cancer should include a multidisciplinary approach and a global geriatric assessment before treatment with anti–HER-2 therapy or bevacizumab.
Determination of Artificial Sweeteners in Beverages and Special Nutritional Products Using High Performance Liquid Chromatography
Authors: Serdar Maja , Knežević Zorka
Published: June 2011

Determination of Artificial Sweeteners in Beverages and Special Nutritional Products Using High Performance Liquid Chromatography

This paper presents two high performance liquid chromatographic (HPLC) methods used for the separation and determination of artificial sweeteners aspartame, acesulphame K, sodium saccharin, and sodium cyclamate in beverages and special nutritional products (special food intended for specific population groups). All four compounds are soluble in aqueous solutions and can easily be separated and determined by HPLC with a diode array detector (DAD). The first method involved separation of aspartame, acesulphame K, and sodium saccharin on a C18 column with an isocratic elution of phosphate buffer and acetonitrile as mobile phase. The second method was used to separate sodium cyclamate on a C18 column with methanol and water as mobile phase. Under optimum conditions, both methods showed good analytical performance, such as linearity, precision, and recovery. The methods were successfully applied for the analysis of real samples of soft drinks and special nutritional products.
Biomonitoring of Human Exposure to Triazine Herbicides
Authors: Mendaš Gordana
Published: June 2011

Biološki Monitoring Izloženosti Ljudi Triazinskim Herbicidima Analizom Metabolita u Urinu

Triazinski herbicidi jedni su od najčešće rabljenih herbicida. Sudbina triazinskih herbicida nakon dospijevanja u okoliš ovisi o njihovu kretanju u zraku, vodi i tlu, kao i o brzini kojom se razgrađuju ili transformiraju. Triazinski spojevi mogu se transformirati reakcijom s vodom, djelovanjem mikroorganizama i utjecajem Sunčeva svjetla. Široka i često nekontrolirana primjena triazinskih herbicida tijekom nekoliko proteklih desetljeća rezultirala je kontaminacijom pitke vode i hrane postajući rizik za opću populaciju. Metabolizam i djelovanje triazinskih herbicida proučavani su na pokusnim životinjama i u uvjetima in vitro, dok je o njihovu metabolizmu i izlučivanju kod ljudi malo objavljenih radova. Djelovanju triazinskih herbicida osobito su izloženi radnici zaposleni u njihovoj proizvodnji i primjeni. Izloženost ljudi prati se i dokazuje određivanjem izvornih spojeva i njihovih metabolita u urinu. Kako se triazinski spojevi u urinu profesionalno izloženih ljudi pojavljuju u niskim koncentracijama, za njihovo dokazivanje i praćenje profesionalne izloženosti potrebno je primijeniti analitičke metode visoke djelotvornosti, osjetljivosti i selektivnosti. U ovom radu opisani su struktura i svojstva simetričnih triazinskih herbicida, njihov metabolizam i djelovanje u organizmu čovjeka i životinja te razine metabolita tih spojeva određene u urinu ispitanika iz profesionalno izložene populacije.
Work Ability Assessment in a Patient with Wilson's Disease
Authors: Popević Martin , Kisić Gordana , Đukić Milenko , Bulat Petar
Published: June 2011

Work Ability Assessment in a Patient with Wilson's Disease

Wilson's disease (WD) is a rare, progressive autosomal recessive disorder characterised by impaired transport and excessive accumulation of copper in the liver, brain, and other tissues. The disease is diagnosed based on clinical manifestations and screening tests results. Work ability assessment of patients with WD is based on the analysis of liver, kidney, neurological, and cognitive impairments, and takes into account patient's level of education.

This article presents a case with a 48-year-old male patient, who was admitted for work ability assessment due to polymorphic symptoms. The patient had been working as a salesman for 28 years. A detailed interview and examination by occupational health and other medical specialists revealed that the patient had been suffering from Wilson's disease from the age of 13, and had now developed hepatic manifestations (compensated liver cirrhosis with portal hypertension), neurological manifestations (dystonia, dysarthria, muscle weakness, vertigo), and psychiatric manifestations (depression, insomnia, cognitive impairment) of the disease, including problems partially caused by long-lasting treatment with copper chelating agents (neurological and haematological manifestations). There were no ocular manifestations of Wilson's disease (Kayser-Fleischer rings or sunflower cataract).

The patient was assessed as having drastically diminished general work ability, dominantly due to neurological and psychiatric impairments caused by Wilson's disease.
Cholinesterases: Structure, Role, and Inhibition
Authors: Bosak Anita , Katalinić Maja , Kovarik Zrinka
Published: June 2011

Kolinesteraze: struktura, uloga, inhibicija

Acetilkolinesteraza (AChE; E.C. 3.1.1.7) i butirilkolinesteraza (BChE; E.C. 3.1.1.8) enzimi su koji se zbog svoje uloge u organizmu intenzivno istražuju unutar područja biomedicine i toksikologije. Iako strukturno homologni, ovi enzimi razlikuju se prema katalitičkoj aktivnosti, odnosno specifičnosti prema supstratima koje mogu hidrolizirati te selektivnosti za vezanje mnogih liganada. U ovom radu dan je pregled dosadašnjih istraživanja kolinesteraza i njihovih interakcija s ligandima i inhibitorima te su izdvojene aminokiseline aktivnog mjesta koje sudjeluju u tim interakcijama.
The relationship between intraseasonal tropical variability and ENSO and its modulation at seasonal to decadal timescales
Authors: Gushchina Daria , Dewitte Boris
Published: June 2011

The intraseasonal tropical variability (ITV) patterns in the tropical troposphere are documented using double space-time Fourier analysis. Madden and Julian oscillations (MJO) as well as equatorial coupled waves (Kelvin and Rossby) are investigated based on the NCEP/NCAR Reanalysis data for the 1977–2006 period and the outputs of an intermediate ocean-atmosphere coupled model named LODCA-OTCM. A strong seasonal dependence of the ITV/ENSO relationship is evidenced. The leading relationship for equatorial Rossby waves (with the correlation of the same order than for the MJO) is documented; namely, it is shown that intensification of Rossby waves in the central Pacific during boreal summer precedes by half a year the peak of El Niño. The fact that MJO activity in spring-summer is associated to the strength of subsequent El Niño is confirmed. It is shown that LODCA-QTCM is capable of simulating the convectively coupled equatorial waves in outgoing long wave radiation and zonal wind at 850 hPa fields with skill comparable to other Coupled General Circulation Models. The ITV/ENSO relationship is modulated at low frequency. In particular the periods of low ENSO amplitude are associated with weaker MJO activity and a cancellation of MJO at the ENSO development phase. In opposition, during the decaying phase, MJO signal is strong. The periods of strong ENSO activity are associated with a marked coupling between MJO, Kelvin and equatorially Rossby waves and ENSO; the precursor signal of MJO (Rossby waves) in the western (central) Pacific is obvious. The results provide material for the observed change in ENSO characteristics in recent years and question whether the characteristics of the ITV/ENSO relationship may be sensitive to the observed warming in the central tropical Pacific.
P-T data of Ky-St-Grt gneisses hosting HP amphibolites and eclogites from the Austroalpine Polinik complex, Kreuzeck Mountains, Eastern Alps, Austria
Authors: Michálek Martin , Putiš Marián , Hauzenberger Christoph
Published: June 2011

This study focuses on metapelites of the Polinik complex in the Kreuzeck Mts. southeast of the Tauern Window, Eastern Alps, where kyanite — staurolite — garnet gneisses host eclogites and high pressure (HP) amphibolites of the Austroalpine basement. The stable mineral assemblage is garnet — staurolite — biotite — kyanite — quartz. Estimated metamorphic conditions from conventional geothermobarometry are 654±30 °C and 0.9±0.08 GPa, and Average P-T values calculated by THERMOCALC, are 665±15 °C at 0.77±0.09 GPa. Formation of the present mineral association in gneisses is related to the exhumation (D2) stage of hosted eclogites/HP amphibolites within a lateral strike-slip zone.
The Occurrence of Major Potato Viruses in Poland
Authors: Kostiw Michał
Published: June 2011

The Occurrence of Major Potato Viruses in Poland

The research was carried out in field conditions in Bonin in the north of Poland, in 1996-2009, and additionally in Bonin, Przechlewo (also in the north of Poland) and Stare Olesno located in the southern part of Poland, in 2008 and 2009. The outcome showed thatPotato virus Yposed the most serious threat to potatoes. The share of progeny tubers infected by this pathogen was 32.5% (mean of 1996-2009) and was considerably higher in comparison to PVM (18.2%) and PVS (22.1%), and in particular to PLRV (15.3%). The additional research carried out in the years 2008 and 2009 in three places: Bonin, Przechlewo (located in the north of Poland) and Stare Olesno (south of Poland) included three potato cultivars of low resistance to PLRV. The results also showed a very low pressure of this virus in both years and in all places of the research. In Przechlewo, PLRV was not detected at all in progeny tubers. While in Stare Olesno and particularly in Bonin, the percentage of PLRV-infected tubers was very small. The average for years and the average for localities amounted to 2.1 and 0.3%, respectively. Whereas the share of tubers infected by PVY, PVM and PVS was considerably higher and ranged from 11.8% to 59.8% depending on the cultivar, year and place. The progeny tubers infected by PVY and PVM were mostly detected in the very early term of exposure(from the 21st of May to the 1st of June). Whereas PVS posed the most serious threat in a somewhat later term i.e. during the exposure of plants which lasted from the 1st of June to 11th of June.