bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Tearing the Intact Anterior Cruciate Ligament in the Contralateral Knee and Rupturing the Anterior Cruciate Ligament Graft during the First 2 Years after Anterior Cruciate Ligament Reconstruction
Authors: Wright Rick W. , Dunn Warren R. , Amendola Annunziato , Andrish Jack T. , Bergfeld John , Kaeding Christopher C. , Marx Robert G. , McCarty Eric C. , Parker Richard D. , Wolcott Michelle , Wolf Brian R. , Spindler Kurt P.
Published: April 2007

Background

The risk of tear of the intact anterior cruciate ligament in the contralateral knee after anterior cruciate ligament reconstruction of the opposite knee and the incidence of rupturing the anterior cruciate ligament graft during the first 2 years after surgery have not been extensively studied in a prospective manner. Clinicians have hypothesized that the opposite normal knee is at equal or increased risk compared with the risk of anterior cruciate ligament graft rupture in the operated knee.

Hypothesis

The risk of anterior cruciate ligament graft rupture and contralateral normal knee anterior cruciate ligament rupture at 2-year follow-up is equal.

Study Design

Cohort study; Level of evidence, 2.

Methods

The Multicenter Orthopaedic Outcome Network (MOON) database of a prospective longitudinal cohort of anterior cruciate ligament reconstructions was used to determine the number of anterior cruciate ligament graft ruptures and tears of the intact anterior cruciate ligament in the contralateral knee at 2-year follow-up. Two-year follow-up consisted of a phone interview and review of operative reports.

Results

Two-year data were obtained for 235 of 273 patients (86%). There were 14 ligament disruptions. Of these, 7 were tears of the intact anterior cruciate ligament in the contralateral knee (3.0%) and 7 were anterior cruciate ligament graft failures (3.0%).

Conclusion

The contralateral normal knee anterior cruciate ligament is at a similar risk of anterior cruciate ligament tear (3.0%) as the anterior cruciate ligament graft after primary anterior cruciate ligament reconstruction (3.0%).
The Effects of Common Anti-Inflammatory Drugs on the Healing Rat Patellar Tendon
Authors: Ferry Scott T. , Dahners Laurence E. , Afshari Hessam M. , Weinhold Paul S.
Published: April 2007

Background

Tendon injuries that occur at the osteotendinous junction are commonly seen in clinical practice and range from acute strain to rupture. Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of these conditions, but the effect that these agents may have on the healing response at the bone-tendon junction is unclear.

Hypothesis

In response to an acute injury at the osteotendinous junction, the healing patellar tendon will have inferior biomechanical properties with administration of anti-inflammatory drugs as compared with acetaminophen and control.

Study Design

Controlled laboratory study.

Methods

A total of 215 Sprague-Dawley rats underwent transection of the patellar tendon at the inferior pole of the patella, which was subsequently stabilized with a cerclage suture. The animals were then randomized into 7 groups and administered 1 of the following analgesics for 14 days ibuprofen, acetaminophen, naproxen, piroxicam, celecoxib, valdecoxib, or control. At 14 days, all animals were sacrificed, and the extensor mechanism was isolated and loaded to failure. Biochemical analysis of the repair site tissue was performed. Animal activity throughout the study was monitored using a photoelectric sensor system.

Results

The control group demonstrated greater maximum load compared with the celecoxib, valdecoxib, and piroxicam groups (P < .05). The acetaminophen and ibuprofen groups were also significantly stronger than the celecoxib group (P < .05) but not statistically different than the control group. A total of 23 specimens had failure of the cerclage suture with the following distribution control (0/23), ibuprofen (0/23), acetaminophen (0/24), naproxen (3/24), piroxicam (4/24), celecoxib (6/22), and valdecoxib (10/24). The difference in distribution of the failures was significant (P < .001).

Conclusions

Anti-inflammatory drugs, with the exception of ibuprofen, had a detrimental effect on healing strength at the bone-tendon junction as demonstrated by decreased failure loads and increased failures of the cerclage suture. Acetaminophen had no effect on healing strength. The biomechanical properties paralleled closely with the total collagen content at the injury site, suggesting that these agents may alter healing strength by decreasing collagen content.

Clinical Relevance

Selective and nonselective cyclooxygenase (COX) inhibitors should be used judiciously in the acute period after injury or surgical repair at the bone-tendon junction.
Can a Double-Row Anchorage Technique Improve Tendon Healing in Arthroscopic Rotator Cuff Repair?
Authors: Charousset Christophe , Grimberg Jean , Duranthon Louis Denis , Bellaiche Laurance , Petrover David
Published: April 2007

Background

Increasing the rate of watertight tendon healing has been suggested as an important criterion for optimizing clinical results in rotator cuff arthroscopic repair.

Hypothesis

A double-row anchorage technique for rotator cuff repair will produce better clinical results and a better rate of tendon healing than a single-row technique.

Study Design

Cohort study; Level of evidence, 2.

Methods

We compared 31 patients undergoing surgery with a double-row anchorage technique using Panalok anchors and Cuff Tack anchors and 35 patients with rotator cuff tear undergoing surgery with a single-row anchorage arthroscopic technique using Panalok anchors. We compared pre- and postoperative Constant score and tendon healing, as evaluated by computed tomographic arthrography 6 months after surgery, in these 2 groups.

Results

The Constant score increased significantly in both groups, with no difference between the 2 groups (P = .4). Rotator cuff healing was judged anatomic in 19 patients with double-row anchorage and in 14 patients with single-row anchorage; this difference between the groups was significant (P = .03).

Conclusion

In this first study comparing double- and single-row anchorage techniques, we found no significant difference in clinical results, but tendon healing rates were better with the double-row anchorage. Improvements in the double-row technique might lead to better clinical and tendon healing results.
Cellular Mechanisms in Sepsis
Authors: Jean-Baptiste Eddy
Published: April 2007

Mortality remains very high among septic patients despite the advanced treatments rendered in intensive care units. The development of septic shock is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Cytokines (tumor necrosis factor, interleukin-1, interleukin-6, interleukin-8, high-mobility group box-1 protein, macrophage migratory inhibitory factor) and noncytokines (nitric oxide, platelet-activating factor, complements, and eicosonoids) may inflict tissue injury and contribute to multiple organ dysfunction and cell death (or apoptosis). Gram-negative bacteria are the most common organisms identified in septic patients. The pathological effects of gram-negative bacteria are conveyed through lipopolysaccharide derived from the bacterial cell membrane. Lipopolysaccharide activates the nuclear factor κ B, which triggers the release of inflammatory mediators. Protein components from gram-positive bacteria, fungi, or viruses may evoke the activation of nuclear factor κ B in a similar fashion as lipopolysaccharide. Endogenous anti-inflammatory mediators are released in response to the infection and act to control the overwhelming systemic inflammatory response. The fragile balance between negative and positive feedback on the inflammatory mediators is the key factor that modulates the cellular damage and influences the clinical outcome.
Critical Care Issues in the Patient After Major Joint Replacement
Authors: Memtsoudis Stavros G. , Rosenberger Peter , Walz J. Matthias
Published: April 2007

Admission rates of orthopedic patients to intensive care units are increasing. Thus, an intensivist's familiarity with specific problems associated with major joint replacement surgery is of utmost importance in order to meet the needs of this particular patient population. In this article, the authors review the most commonly encountered complications after major hip and knee arthroplasty. Perioperative risk factors for morbidity and mortality and the epidemiology, diagnosis, and treatment of cardiopulmonary complications in this patient population are discussed. Procedure-specific complications such as fat embolism and acrylic bone cement—related issues are reviewed.
The Practice of Platelet Transfusion in the Intensive Care Unit
Authors: Salman Salam S. , Fernández Pérez Evans R. , Stubbs James R. , Gajic Ognjen
Published: April 2007

The practice of platelet transfusion in the intensive care unit varies, and liberal use may not be associated with improved outcome. This study reviewed the medical records of 117 patients with moderate-to-severe thrombocytopenia and without active bleeding who were admitted to intensive care unit beds during a 6-month period. The primary outcome measures were new bleeding episodes and platelet transfusion complications. Ninety (77%) received a platelet transfusion. Significant new bleeding developed in 1 patient who received a transfusion. Six patients (8%) developed transfusion complications: 2 transfusion-related acute lung injury, 2 allergic, and 2 febrile reactions. Patients who did not receive platelet transfusion had a higher severity of illness than transfused patients. Predictors of platelet transfusion were platelet count and postoperative status, but not invasive procedure. The practice of platelet transfusion in critically ill patients with thrombocytopenia varies. Prospective studies evaluating restrictive versus liberal platelet transfusion strategies are warranted.
Acute Adrenal Insufficiency After a Single Dose of Etomidate
Authors: Lundy Jonathan B. , Slane Matthew L. , Frizzi James D.
Published: April 2007

Acute adrenocortical insufficiency is a critical care emergency characterized by hemodynamic instability, lethargy, and cardiovascular collapse. Acute adrenal insufficiency has many etiologies, from rapid withdrawal of exogenous glucocorticoids to adrenocortical destruction to poor adrenal reserve after administration of steroid synthesis inhibitors. Etomidate, a parenteral hypnotic agent, is a steroid synthesis inhibitor. Although the use of continuous etomidate infusion in the intensive care unit fell from favor secondary to reports of adrenal crisis, single-dose etomidate for induction of anesthesia is common for the hemodynamically unstable patient or in patients who may not tolerate wide variance in heart rate or blood pressure. A case is presented of acute adrenocortical insufficiency and crisis after a standard induction dose of etomidate. Acute adrenal insufficiency should be suspected in intensive care unit patients who have undergone general anesthesia with etomidate induction and present with hypotension refractory to standard vasopressor administration.
The Morning After
Authors: Damphousse Kelly R. , Shields Chris
Published: April 2007

A major terrorism event has several important consequences for officials involved in the investigation and prosecution of terrorist activities. Such events are likely to bring increased scrutiny by both public policy officials and the media. The article uses data from the American Terrorism Study to compare the period before and after two of the most dramatic terrorist events on U.S. soil: the Oklahoma City bombing and the 9/11 attacks. The results suggest that whether intentional or not, major terrorism events result in the government's pursuing cases that are generally less serious and less complicated, and those cases are treated much more like “traditional” crimes by the prosecution. Following the aftermath of a major event, terrorist defendants are more likely to behave like traditional offenders and are less likely to be convicted as a result of a trial than are terrorists who are indicted before major events.
Respiratory Periodicity and Electroencephalogram Arousals During Sleep in Older Adults
Authors: Waag Carlson Barbara , Neelon Virginia J. , Carlson John R. , Hartman Marilyn , Dogra Sunil
Published: April 2007

The aim of this exploratory study was to examine the relationship of electroencephalogram (EEG) arousals to breathing patterns and the relationship of both arousals and breathing patterns to arterial oxygenation during sleep in older adults. Five older adults were monitored using standard polysomnography. Records were divided into 5-min segments and breathing patterns identified based on the level of respiratory periodicity and the variability in the frequency of breathing cycles. Standard criteria were used to determine sleep states and occurrence of EEG arousals. High respiratory periodicity was seen in 23% of the segments, whereas 24% had low respiratory periodicity with minimal variability in the frequency of breathing (Type A low respiratory periodicity) and 53% had low respiratory periodicity with high variability in the frequency of breathing (Type B low respiratory periodicity). Nearly all (97%) segments with high respiratory periodicity had EEG arousals, whereas fewer segments (33%) with low respiratory periodicity had arousals, regardless of the stage of sleep. Desaturations occurred more often in segments with high respiratory periodicity, F (2,4) = 57.3, p < .001, but overall, the mean SaO2 of segments with high respiratory periodicity did not differ from levels seen in segments with low respiratory periodicity, F( 2,4) = 0.77, ns. Our findings suggest that high respiratory periodicity is a common feature of EEG arousals and, in older adults, may be important for maintaining oxygen levels during desaturations during sleep.
Fetal Development: Voice Processing in Normotensive and Hypertensive Pregnancies
Authors: Lee C.T. , Brown C.A. , Hains S.M.J. , Kisilevsky B.S.
Published: April 2007

Recent observation of maternal voice recognition provides evidence of rudimentary memory and learning in healthy term fetuses. However, such higher order auditory processing has not been examined in the presence of maternal hypertension, which is associated with reduced and/or impaired uteroplacental blood flow. In this study, voice processing was examined in 40 fetuses (gestational ages of 33 to 41 weeks) of hypertensive and normotensive women. Fetuses received 2 min of no sound, 2 min of a tape-recorded story read by their mothers or by a female stranger, and 2 min of no sound while fetal heart rate was recorded. Results demonstrated that fetuses in the normotensive group had heart rate accelerations during the playing of their mother's voice, whereas the response occurred in the hypertensive group following maternal voice offset. Across all fetuses, a greater fetal heart rate change was observed when the amniotic fluid index was above compared to below the median (i.e., 150 mm), indicating that amniotic fluid volume may be an independent moderator of fetal auditory sensitivity. It was concluded that differential fetal responding to the mother's voice in pregnancies complicated by maternal hypertension may reflect functional elevation of sensorineural threshold or a delay in auditory system maturation, signifying functional differences during fetal life or subtle differences in the development of the central nervous system.
Heart Rate Variability in Premature Infants During Feeding
Authors: Brown Lisa
Published: April 2007

Early mother-infant interaction, a potentially major contributor to the development of a premature infant's behavioral and physiologic regulation, has received very little research attention. This study examined the development of physiologic regulation in relation to maternal-infant feeding interaction for 43 premature infants, from the time caregiving responsibility was transferred to the mother through each infant's 4th postterm month. Infants and mothers were seen in a special care nursery just before discharge and in home at 1 and 4 months postterm age. General linear mixed models were used to examine the changes in infant heart rate variability (HRV) and Positive Affective Involvement and Sensitivity/Responsiveness scores over time and infant HRV over feeding conditions (prefeeding, feeding, and postfeeding). Significant differences were found for high-frequency and low-frequency HRV over time (p < .001 and p = .014, respectively). However, maternal feeding behavior did not show a significant effect of time (p = .24). The feeding condition effect on high-frequency HRV was significant (p < .001), with HRV lower during feeding compared to both prefeeding and postfeeding. Maternal feeding behavior was not associated with infant HRV. Discovering the ways in which maternal feeding behavior contributes to infant physiologic regulation may require study of the relationship of HRV to infant feeding behavior.
The Effect of Kappa Opioid Receptor Antagonism on Energy Expenditure in the Obese Zucker Rat
Authors: Jarosz Patricia A.
Published: April 2007

Food intake and, subsequently, body weight are influenced by endogenous opioids acting in the central nervous system. Agonists for the opioid receptor increase food intake, whereas antagonists reduce food intake. Body weight, however, is the result of food consumed and energy expended. Although much has been reported about the effect of opioid antagonism on food intake, less has been reported about its effect on energy expended. This study investigated the effect of selective antagonism of the kappa opioid receptor on food intake, body weight, and indicators of energy expenditure in male obese Zucker rats (n= 10). Energy expenditure was measured by indirect calorimetry, whereas general activity and body temperature were measured by implanted radio frequency telemetry. Central administration of 30 µg of the kappa opioid receptor (KOR) antagonist norbinaltorphamine resulted in a significant 34% reduction in food intake (p = .001), a small reduction in body weight, a reduction in resting energy expenditure (p = .06), a reduction in respiratory quotient (p = .06), a 14% reduction in general activity, and a reduction in core body temperature. Reduction in body weight as a result of KOR inhibition in this study was related to a decrease in food intake but not related to an increase in energy expended or activity.
Methods of Measuring Insulin Sensitivity
Authors: Trout Kimberly K. , Homko Carol , Tkacs Nancy C.
Published: April 2007

Insulin resistance is a component of several health disorders, most notably impaired glucose tolerance and type 2 diabetes mellitus. Insulin-resistant individuals have an impaired biological response to the usual action of insulin; that is, they have reduced insulin sensitivity. Various methods are used to assess insulin sensitivity both in individuals and in study populations. Validity, reproducibility, cost, and degree of subject burden are important factors for both clinicians and researchers to consider when weighing the merits of a particular method. This article describes several in vivo methods used to assess insulin sensitivity and presents the advantages and disadvantages of each.
Local Claims to Fame
Authors: Bell Claudia
Published: April 2007

Throughout New Zealand, giant roadside objects—sheep, cows, dogs—and murals depicting local history denote local claims to fame. As a collection, these artifacts tell the rural sector's story of agriculture and productivity. The 1980s rural downturn led to a declining rural population and a perceived declining status of rural dwellers. The ongoing construction of place markers indicates that the need to express identity is a continuous project. In the face of the huge competition for markets and for media attention, as a consequence of globalization, local residents draw from what they know best: versions of their own history and of local character.
Mobile Homes
Authors: Bell David , Hollows Joanne
Published: April 2007

This article considers the relationships between mobility and immobility in the context of food and cooking. It focuses on the construction of the domestic as a gendered, ethnicized, and classed space of immobility through which others experience “real” or “virtual” travel. These themes are explored through three examples: Vicky Bhogal's recipe book Cooking like Mummyji , the TV series by celebrity chef Jamie Oliver, Jamie's Great Escape , and the Slow Food movement. In each case, the authors discuss who is mobile and who is fixed and show how ideas of home, tradition, local, and authentic are located through the cooking practices of particular figures. Through this discussion, the authors aim to highlight how immobility operates as a crucial reference point in contemporary images and discourses of globalized culinary culture.
Remembering Laredo
Authors: Momen Mehnaaz
Published: April 2007

This article explores the public spaces of Laredo, a city situated on the border of the United States and Mexico along the Rio Grande. The construction of urban history is shaped by changes in public space—its physical settings, access to residents, and utilization by people. The author analyzes the transformation of public spaces and public events of Laredo to trace how amnesia and remembering are reflected in the cityscape. Public events reproduce assorted versions of urban history and help scholars to locate what part of history is preserved and what part is erased in the collective psyche of the community. The visual history of public spaces and events thus conserves a narration of the past, one that shapes collective memory and self-image.
Food Mobilities
Authors: Gibson Sarah
Published: April 2007

This article explores how food is good to think mobilities with. Food, taste, and eating are all implicated in differing mobilities, whether corporeal, technological, imaginative, or virtual. The space of the dining car brings together the corporeal mobility of passengers, the technological mobility of the railways, and the mobility of food. Through the reflections of eating in the dining car by E. M. Forster and Roland Barthes, this article explores this particular experience of eating on the move, before examining how cultures of food and eating are central to experiences of “traveling-indwelling” and “dwelling-in-traveling” through the wider connections of food mobilities.
Socialization and the Business School
Authors: Harney Stefano
Published: April 2007

There is a new phase in the generalization of management capacities, but contrary to the assumptions of critical management educators, the investment in the business school has not been to socialize more students into this generalized management, but to seek the principle of generalization in these students themselves as part of a struggle between capital and labour. Using the insights of autonomist feminist theorists, this article attempts to analyse why critical management education has been unable to find a new object appropriate to this new generalization of management, and speculates on what the critical and political benefits might be of escaping older notions of the business school as a site of socialization for a social categor y of managers.
Researching Situated Learning
Authors: Handley Karen , Clark Timothy , Fincham Robin , Sturdy Andrew
Published: April 2007

Situated learning theory has emerged as a radical alternative to conventional cognitivist theories of knowledge and learning, emphasizing the relational and structural aspects of learning as well as the dynamics of identity construction. However, although many researchers have embraced the theoretical strengths of this perspective, methodological and operational issues remain undeveloped in the literature. This article seeks to address these deficiencies by developing a conceptual framework informed by situated learning theory and by investigating the methodological implications. The framework is applied in the context of an empirical study of how management consultants learn the practices and identities appropriate to client—consultant projects. By presenting two vignettes and interpreting them using the conceptual framework, we show how learning is regulated by the consulting firm as well as individuals themselves, and that, paradoxically, `failure to learn' may be an outcome of consultants' efforts to construct a coherent sense of self.
Space, Vision and Organizational Learning
Authors: Edenius Mats , Yakhlef Ali
Published: April 2007

The concept `open-plan office' has captured the corporate imagination. Most research in the area assumes that spatial layouts of work places enhance social interaction and communication among individuals, thereby facilitating learning, sharing and transfer of knowledge. However, absent from these discussions is the significance of visual aspects of space. Drawing on case studies, the article attempts to highlight the link between the visual, perceptual features of space and effects on organizational learning. Whereas Foucauldian vision models over-emphasize inscribing practices in the learning process, this article argues for the significance of incorporating spatial practices, suggesting that organizational learning is the outcome of an interplay of incorporating and inscribing practices. Incorporating practices, as responses to a body in a perceptual space, produce inscriptions that congeal into organizational learning, organizational rules, procedures and routines, and involve an intertwining of vision and movement, of active engagement of the body with the physical environment.
Simulating Entrepreneurial Learning
Authors: Pittaway Luke , Cope Jason
Published: April 2007

Theorizing about entrepreneurial learning is examined in this article to determine key learning processes within this body of research. It explores how these processes might be simulated in a student-learning environment and highlights the role of emotional exposure, situated learning, action-orientation and discontinuity. An argument is made for experiential, work-based learning when seeking to simulate contexts similar to those in which entrepreneurs learn. A conceptual framework is introduced that highlights a course design based on the factors identified. In the analysis, formal course assessments are reviewed and narrative coding based on student reflections is evaluated. The article illustrates that it is possible to simulate aspects of entrepreneurial learning, such as emotional exposure and situated learning, but not others. It also demonstrates a range of learning benefits linked to experiential learning. In conclusion, the article explains why entrepreneurship education can play an important role in encouraging management learning.
Continuing Professional Development in the Legal Profession
Authors: Gold Jeff , Thorpe Richard , Woodall Jean , Sadler-Smith Eugene
Published: April 2007

Continuing professional development is often seen as a means of protecting professional autonomy and maintaining privileged status. This article explores recent debates. A missing perspective on how professional learning occurs is explored using practice-based learning. The purposeful practice of professionals is considered with particular attention to instances of `hot' action, situations where professionals are required to make on-the-spot decisions with little time for deliberation. We demonstrate that it is at such moments that, through articulation and in dialogic relations, professionals can arrive at new understandings of their work; this we term `CPD-on-the-run'. Our research findings are from a collaborative study of lawyers and we report some of the significant ways in which these professionals learn and the context. Our findings suggest there is a need to shift policies away from the predominant focus on individuals towards a concern with informal and spontaneous collective interaction in practice.
Mindfulness-Based Cognitive Attitude Training for Primary Care Staff: A Pilot Study
Authors: Schenström Anna , Rönnberg Sten , Bodlund Owe
Published: April 2007

This pilot study explores feasibility and outcomes of a newly developed mindfulness-based cognitive attitude training program for health care personnel. The program was designed as an intervention to reduce the negative effects of stress on health care personnel, on both a personal and professional level, as well as to encourage personal well-being and improved management of the caregiver-patient relationship. The study group ( n = 52) consisted of individuals from various categories of caregivers within a primary care setting. The study includes pre- and postintervention assessments and a 3-month follow-up assessment of levels of mindfulness (Mindfulness Attention Awareness Scale), quality of life (the WHO-5 Well-Being Questionnaire), and perceived stress (two VAS scales). As a group, course participants demonstrated significant positive changes reflected in all assessment scales after completing the course. These positive changes persisted at a 3-month follow-up assessment. The study results indicate the feasibility of this program and a need for continued research with a more powerful study design, possibly supplemented with a qualitative survey.
A Proposal for a Mindfulness-Based Trauma Prevention Program for Social Work Professionals
Authors: Berceli David , Napoli Maria
Published: April 2007

The pervasiveness of traumatic events and the increasing awareness of their persistent and sometimes devastating effects on individuals and populations has repositioned trauma from a peripheral topic of interest for social workers to a mainstream subject of study. This article explores the personal and professional challenges that mass trauma presents to social workers and provides a rationale for, and description of, a proposed mindfulness-based trauma prevention program. This program is designed to guide social workers and other health professionals in learning effective self-directed techniques to maintain equanimity in the face of danger and human suffering, thereby reducing the incidence of secondary trauma and posttraumatic stress disorder. Components of the program include mindfulness of breathing, body scan, and trauma-releasing exercises.
Acupuncture for Birth Preparation and Delivery: How Investigating Mechanisms of Action Can Generate Research
Authors: Curtis Peter , Coeytaux Remy R. , Hapke Patrice
Published: April 2007

Acupuncture has become an accepted and validated part of Western mainstream medicine and is increasingly used by clinicians, midwives, and acupuncturists for reproductive care, induction of labor, and analgesia. Most studies of the effects of obstetrical acupuncture are descriptive, many in foreign languages. Only a few have evaluated efficacy. Results suggest that acupuncture ripens the cervix, initiates labor, reduces labor pain, and shortens the first stage of labor. There is some evidence suggesting that certain acupuncture points have very specific effects on the fetus and uterus, which may be mediated through the hypopituitary-thalamic axis or by local neurovascular stimulation. The substantial maternal hormonal changes occurring just before and during labor offer a unique opportunity to clarify the mechanisms of action of acupuncture. Using a conceptual model based on possible mechanisms of action of the use of acupuncture in obstetrics, the authors propose specific research questions into the physiology of acupuncture administered before and at parturition.
Cost-effectiveness in clinical trials: using multiple imputation to deal with incomplete cost data
Authors: Burton Andrea , Billingham Lucinda Jane , Bryan Stirling
Published: April 2007

Background Cost-effectiveness has become an important outcome in many clinical trials and has resulted in the collection of resource use data and the calculation of costs for individual patients. A specific example is a Cancer Research UK phase III trial comparing chemotherapy (CT) against standard palliative care in patients with advanced non-small cell lung cancer. Resource usage from trial entry until death were collected and costs obtained on a subset of 115 trial patients. For some patients, however, the unavailability of medical notes resulted in some cost components, and hence total cost, being missing. The 82 patients with complete data were not representative of all trial patients in terms of effectiveness and thus it was necessary to address the missing data problem.

Methods Multiple imputation (MI) was used to impute values for the unobserved individual cost components, allowing total cost to be calculated and cost-effectiveness carried out for all patients in the cost sub-study. The results are compared with those from a complete case analysis.

Results After MI, the results indicated that CT had a high probability of being cost-effective for a societal willingness to pay over £20 000 per life-year gained. This was in stark contrast with the complete case analysis, which suggested that CT was not a cost-effective use of resources at any reasonable level of willingness to pay for a life-year.

Limitations Our findings are based on a relatively small retrospective study with all events observed.

Conclusion In conclusion, cost-effectiveness analysis of the complete cases only may give biased results, and therefore, in situations where there are missing costs, MI is recommended. Clinical Trials 2007; 4: 154—161. http://ctj.sagepub.com
A decision rule for sequential monitoring of clinical trials with a primary and supportive outcome
Authors: Zhao Yanli , Grambsch Patricia M. , Neaton James D.
Published: April 2007

Background Many clinical trials have multiple outcomes. Formal interim monitoring guidelines that take account of multiple outcomes can be useful to Data Monitoring Committees (DMC). Previous research has focused on marginal criteria that control the overall type I error for bivariate endpoints corresponding to efficacy and safety. Usually, an `or' decision rule is used, that is, the trial is stopped when either the safety or the efficacy endpoint crosses a boundary.

Purpose In many trials there is not a clear difference between what is considered a safety and an efficacy endpoint. Likewise, in some studies there is interest in more than one disease outcome and while there may be a primary efficacy endpoint, interim monitoring might also involve a measure of overall health. For these situations, an `and' decision rule might be more appropriate; that is, the trial is stopped only when both endpoints cross a boundary. Formulation of this new decision rule at the design stage would encourage more discussion among trial investigators of monitoring guidelines and would result in improved guidelines for DMCs.

Methods In this paper, we propose stopping guidelines for such trials with two major outcomes that control the overall type I error and stop early only if both endpoints indicate superiority for the same treatment. Trials with two treatments are considered and we develop sets of paired two-sided boundaries, permitting one endpoint to be primary and the other supportive, with or without pre-specifying which one is primary.

Results The results show that the boundaries depend on the correlation between the two outcomes. The critical values increase as the correlation increases in most cases. For low to moderate correlation and before the last stage, critical values based on the O'Brien Fleming (or Pocock) error spending function that consider the correlation are lower than those which do not.

Limitations Investigators might not want to stop a trial early with the small size of the critical values that result from this decision rule for some situations. For a trial in which the treatment effect for one outcome is large, while for the other it is small, the proposed decision rule has low power to accept this treatment for its superiority on both outcomes. Also, we do not provide a separate P-value for each outcome since type I error is not controlled for individual null hypotheses.

Conclusions For trials involving two major health outcomes these stopping guidelines may be appropriate for DMCs when the trial investigators and sponsor recommend that early termination not be considered unless the findings are consistent for both outcomes. Clinical Trials 2007; 4: 140—153. http://ctj.sagepub.com
Statistical design of THRio: a phased implementation clinic-randomized study of a tuberculosis preventive therapy intervention
Authors: Moulton Lawrence H. , Golub Jonathan E. , Durovni Betina , Cavalcante Solange C. , Pacheco Antonio G. , Saraceni Valeria , King Bonnie , Chaisson Richard E.
Published: April 2007

Background Tuberculosis (TB) is a major public health problem in Rio de Janeiro, where a high proportion of HIV-infected adults are co-infected with latent TB. Health officials in Brazil have recommended that HIV patients be tested for TB infection and given TB prophylaxis (isoniazid) if positive. In practice, although Brazil is a model for provision of antiretroviral therapy to patients with advanced HIV disease, relatively few such patients receive TB testing and prevention services.

Purpose We initiated a randomized study of a health services intervention to train health personnel in implementation of the recommended routine of TB testing and isoniazid prophylaxis. The primary goal is to reduce incident TB disease in the HIV clinic population.

Methods The clinic-level intervention will be phased in gradually over the study period until all clinics have received the intervention. The clinics' order of initiation of intervention was randomized and subjected to constraints based on clinic-level covariates. This phased intervention cluster-randomized trial required special attention to power/sample size calculation and randomization procedures, of which we provide the relevant details.

Results Special design considerations accounted for within-clinic correlation, variation in the clinic size, time-varying ratio of intervention to control clinics and guaranteed post-randomization covariate balance. These were successfully implemented for the estimation of power and execution of the randomization strategy.

Limitations Although the design features of randomization by clinic and phased implementation of the intervention meet logistic and local needs, they substantially lower the statistical power of the study.

Conclusions Studies with cluster-randomized order of intervention introduction can provide useful information on intervention effects. Their design and analysis are more complicated than for individually randomized parallel design trials. The methods we describe represent practical approaches to the challenges raised in the course of designing this study. Clinical Trials 2007; 4: 190—199. http://ctj.sagepub.com
Eliciting and using expert opinions about dropout bias in randomized controlled trials
Authors: White Ian R , Carpenter James , Evans Stephen , Schroter Sara
Published: April 2007

Background The analysis of clinical trials with dropout usually assumes the missing data are `missing at random', i.e. given an individual's past observed data, their probability of dropout does not depend on their present outcome. However, in many settings this assumption is implausible, so it is sensible to assess the robustness of conclusions to departures from missing at random.

Purpose To develop a practical, accessible, approach that allows expert opinions about the degree of departure from missing at random in the analysis of a clinical trial to be meaningfully and accurately elicited and incorporated in sensitivity analysis.

Methods We elicit experts' prior beliefs about the mean difference between missing and observed outcomes in each trial arm. Then we perform a Bayesian synthesis of the information in the trial data with that in the experts' prior, using (i) a full Bayesian analysis for which we give WinBUGS code, and (ii) a simple approximate formula for the estimated treatment effect and its standard error. We illustrate our approach by re-analysing a recent trial of interventions to improve the quality of peer review.

Results In the peer review trial, the approximate formula agreed well with the full Bayesian analysis, and both showed substantially larger standard errors than an analysis assuming missing at random.

Limitations Strictly, the method is only applicable if the outcome is normally distributed. We did not elicit the full bivariate prior distribution, and instead used a sensitivity analysis. Our approach is not designed to incorporate prior beliefs about the intervention effect itself.

Conclusions Our proposed approach allows for the greater uncertainty introduced by missing data that are potentially informatively missing. It can therefore claim to be a truly conservative method, unlike methods such as `last observation carried forward'. It is practical and accessible to non-statisticians. It should be considered as part of the design and analysis of future clinical trials. Clinical Trials 2007; 4: 125—139. http:/ctj.sagepub.com
Contrasts in gem corundum characteristics, eastern Australian basaltic fields: trace elements, fluid/melt inclusions and oxygen isotopes
Authors: Zaw Khin , Sutherland F. L. , Dellapasqua F. , Ryan C. G. , Yui Tzen-Fu , Mernagh T. P. , Duncan D.
Published: April 2007

Corundum xenocrysts from alkaline basalt fields differ in characteristics and hence lithospheric origins. Trace element, fluid/melt inclusion and oxygen isotope studies on two eastern Australian corundum deposits are compared to consider their origins. Sapphires from Weldborough, NE Tasmania, are magmatic (high-Ga, av. 200 ppm) and dominated by Fe (av. 3300 ppm) and variable Ti (av. 400 ppm) as chromophores. They contain Cl, Fe, Ga, Ti and CO2-rich fluid inclusions and give δ18O values (5.1–6.2‰) of mantle range. Geochronology on companion zircons suggests several sources (from 290 Ma to 47 Ma) were disrupted by basaltic melts (47 ± 0.6 Ma). Gem corundums from Barrington, New South Wales, also include magmatic sapphires (Ga av. 170 ppm; δ18O (4.6–5.8‰), but with more Fe (av. 9000 ppm) and less Ti (av. 300 ppm) as chromophores. Zircon dating suggests that gem formation preceded and was overlapped by Cenozoic basaltic melt generation (59–4 Ma). In contrast, a metamorphic sapphire-ruby suite (low-Ga, av. 30 ppm) here incorporates greater Cr into the chromophores (up to 2250 ppm). Fluid inclusions are CO2-poor, but melt inclusions suggest some alkaline melt interaction. The δ18O values (5.1–6.2‰) overlap magmatic sapphire values. Interactions at contact zones (T= 780–940°C) between earlier Permian ultramafic bodies and later alkaline fluid activity may explain the formation of rubies.
JAK2 617V>F–positive polycythemia rubra vera maintained by approximately 18 stochastic stem-cell divisions per year, explaining age of onset by a single rate-limiting mutation
Authors: Vickers Mark A.
Published: April 2007

As the rates of most cancers are proportional to the fourth to fifth power of age (“log-log” behavior), it is widely believed that 5 to 6 independent mutations are necessary for malignant transformation. Conversely, the peak incidences of most cancers are similar to stem-cell mutation rates at single loci, implying only one rate-limiting mutation. Here, flow cytometrically measured red blood cells mutated at a selectively neutral locus, glycophorin A, allow observation of individual stem-cell differentiation events in a log-log malignancy, polycythemia rubra vera. Contrary to predictions from multistep models, the clone is driven by infrequent (< annual) and rare (∼ 18 per year) differentiation events. These parameters imply that malignant stem cells have a modest selective advantage. Correspondingly minor, typically less than 20%, increases in stochastic self-renewal ratios are modeled to show that single mutations can result in the observed fourth power relationship with age. The conundrum between log-log behavior and mutation rate is thereby reconcilable, with the age of onset arising not from the requirement for multiple, independent mutations but from infrequent, stochastic stem-cell division rates and single mutations causing initially minor effects, but initiating a clone whose expected number increases successively with age—an “exponential phenotype.”
TREM-1 ligand expression on platelets enhances neutrophil activation
Authors: Haselmayer Philipp , Grosse-Hovest Ludger , von Landenberg Philipp , Schild Hansjörg , Radsak Markus P.
Published: April 2007

The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leukocyte (PMN) effector functions (provoked by LPS). However, TREM-1 interaction with its ligand is not required for platelet/PMN complex formation, which is dependent on integrins and selectins. Taken together, the results indicate that the TREM-1 ligand is expressed by platelets, and the TREM-1/ligand interaction contributes to the amplification of LPS-induced PMN activation. Our results shed new light on our understanding of TREM-1 and its role in the innate inflammatory response in infections and might contribute to the development of future concepts to treat sepsis.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study
Authors: Nash Richard A. , McSweeney Peter A. , Crofford Leslie J. , Abidi Muneer , Chen Chien-Shing , Godwin J. David , Gooley Theodore A. , Holmberg Leona , Henstorf Gretchen , LeMaistre C. Fred , Mayes Maureen D. , McDonagh Kevin T. , McLaughlin Bernadette , Molitor Jerry A. , Nelson J. Lee , Shulman Howard , Storb Rainer , Viganego Federico , Wener Mark H. , Seibold James R. , Sullivan Keith M. , Furst Daniel E.
Published: April 2007

More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, −22.08; P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, −1.03; P < .001) at final evaluation. Importantly, for the first time, biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial.