Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients

Summary. Background: Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out‐of‐range International Normalized Ratio (INR) values and adverse events are common. Methods: In orthopedic patients beginning warfarin therapy, we developed and prospectively validated pharmacogenetic and clinical dose refinement algorithms to revise the estimated therapeutic dose after 4 days of therapy. Results: The pharmacogenetic algorithm used the cytochrome P450 (CYP) 2C9 genotype, smoking status, peri‐operative blood loss, liver disease, INR values and dose history to predict the therapeutic dose. The R² was 82% in a derivation cohort (n = 86) and 70% when used prospectively (n = 146). The R² of the clinical algorithm that used INR values and dose history to predict the therapeutic dose was 57% in a derivation cohort (n = 178) and 48% in a prospective validation cohort (n = 146). In 1 month of prospective follow‐up, the percent time spent in the therapeutic range was 7% higher (95% CI: 2.7–11.7) in the pharmacogenetic cohort. The risk of a laboratory or clinical adverse event was also significantly reduced in the pharmacogenetic cohort (Hazard Ratio 0.54; 95% CI: 0.30–0.97). Conclusions: Warfarin dose adjustments that incorporate genotype and clinical variables available after four warfarin doses are accurate. In this non‐randomized, prospective study, pharmacogenetic dose refinements were associated with more time spent in the therapeutic range and fewer laboratory or clinical adverse events. To facilitate gene‐guided warfarin dosing we created a non‐profit website, http://www.WarfarinDosing.org .     

Computer simulation of clinical electrophysiological study

Background: Computer simulation is an important method for the basic researches of cardiac electrophysiology to prove the mechanisms and hypotheses of cardiac arrhythmias by reproducing body surface electrocardiograms. In this research, we extend the researches of heart models to the computer simulation of clinical electrophysiological study (EPS) as a clinical application of heart models. Method: Through setting the standard EPS pacing protocols, including extrastimuli and incremental pacing in the heart models, we simulated the corresponding excitation propagations in the heart and the intracardiac electrograms that would be measured with catheter electrodes. Results: Examples of complicated cases observed during EPS are reproduced in this research, including the induction of a Wenckebach pattern, the induction and termination of supraventricular tachycardia due to the reentry loop of antidromic atrioventricular reentrant tachycardia for the Wolff‐Parkinson‐White (WPW) syndrome (Type A), and the localization of an accessory pathway for the WPW syndrome (Type A). Conclusion: This study demonstrates an application of whole‐heart modeling and computer simulation to clinical EPS. (PACE 2012; 35:718–729)     

Student–clinician agreement in clinical competence as a predictor of clinical placement performance in Australian undergraduate physiotherapy students

Objectives: The opportunity for student self-reflection and the accuracy of that reflection are critical to the acquisition of professional competencies. The relationship between student–clinician agreement and clinical performance in physiotherapy students has not yet been investigated. The aim was to determine whether a simple measure of student–clinician agreement assessed midway during a clinical placement predicts final placement score. Participants: 100 undergraduate Monash University Bachelors of Physiotherapy students and their clinical educators. Main outcome measures: Assessment of Physiotherapy Practice (APP). Method: Clinician and student ratings of student performance across all clinical placements from January 2012–June 2013 at two time-points (midway and final) were entered into a purpose-built, web-based platform, and then averaged across the number of placements undertaken. The relationship between midway student–clinician agreement (student minus clinician APP score) and final APP score (determined by the clinician) was analyzed via forward regression. Sub-group comparisons were performed investigating the stability of the relationship across placements. Results: On average, midway agreement was associated with a ?0.50 (95% CI ?0.67 to ?0.33) unit decrease in final placement APP% score. This model was highly statistically significant (p < 0.001) but only explained 24% of the total variance (based on the adjusted r-squared statistic). This relationship was similar in early and late placements. Conclusions: Student–clinician agreement is related to clinical performance. A midway evaluation may provide an important opportunity to identify students “at risk” of poor clinical outcomes enabling timely implementation of support strategies. Further work is required to improve the predictive accuracy of the proposed model.     

Mesenchymal stem cells: biological properties and clinical applications

Importance of the field: In the last decade, knowledge of mesenchymal stem cells (MSCs) has evolved rapidly; their immunomodulatory properties and paracrine interactions with specific cell types in damaged tissues and promising results in some clinical applications have made these cells an attractive option for the treatment of certain diseases.

Areas covered in this review: We present some relevant methodological issues and biological properties of MSCs, as well as clinical applications of MSC therapies with particular emphasis in the treatment of graft versus host disease (GVHD), complex perianal fistula and refractory metastatic neuroblastoma. Other topical aspects relevant to the application of cellular therapies such as biosafety studies and cellular production of MSCs are also discussed in this review.

What the reader will gain: The growing optimism regarding MSCs research is based on the promising results obtained in in vitro and in vivo studies. The rapid translational research with MSCs necessitated standardization of methodology and terminology and greater focus on other aspects such as biosafety and cellular production, especially for clinical use of MSCs.

Take home message: Much has been learned about the biology and applications of MSCs and much remains to be learned.     

Differences in clinical presentation of deep vein thrombosis in men and women

Summary. Background: As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women. Objectives: To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT. Methods: A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients. Results: The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P = 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%; P = 0.025) or moderate (16.9% vs. 8.7%; P = 0.04), but similar in patients in the high category (40.2% vs. 44.0%; P = 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%; P < 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men. Conclusions: In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.     

Pharmacology and clinical applications of human recombinant antithrombin

Importance of the field: Antithrombin therapy (AT) has been tested in various medical applications. With advances in genetics and biotechnology, large-scale production of human recombinant antithrombin (rhAT) is now feasible. The prospect of administering a recombinant protein rather than a pooled blood component, has rekindled interest in antithrombin therapy. However, many known properties of human pooled antithrombin (hpAT) still need to be investigated and established for rhAT.

Areas covered in this review: The manufacture and clinical pharmacology of antithrombin. The literature, evidence and our own views about the future of this drug and its potential clinical applications.

What the reader will gain: The reader will appreciate the biological rationale underpinning antithrombin administration in various clinical settings. The potential benefits and harms of the intervention are addressed. Novel future applications of recombinant antithrombin are broached.

Take home message: rhAT has been approved for its use in congenital antithrombin deficiency. rhAT has also been used off-label to treat heparin-resistance in cardiac surgery and sepsis. It is a promising adjuvant for immunosuppression in organ transplantation, and may have role as an anti-angiogenic, anti-tumor and anti-viral agent. rhAT has clear safety advantages over phAT, such as the avoidance of infection transmission.     

Practice nurses' sources of clinical support: observations from a citywide survey

Objectives: The survey aimed to identify present sources, and perceived adequacy, of clinical support amongst local practice nurses.Design: Telephone survey and focus group.Setting: Practice Nurses employed in a General Practice setting supported by reimbursement from the Manchester Health Authority.Participants: Telephone survey—75 practice nurses, ten data collectors. Focus group—6 Practice Nurses, Primary Care Nurse Advisor and a Researcher.Main outcome measures: Survey results aimed to identify frequency of and sources of clinical support amongst all local practice nurses and their understanding of the term Clinical Supervision. Focus group explored fine detail and ‘puzzlements’ arising from survey.Findings:General practitioners are the main source of clinical support for practice nurses. The practice nurses preferred an informal approach to clinical support with the nurse remaining in control of the process, seeking support when needed. All respondents expressed strong concerns that the professional autonomy that they associate with practice nursing should be protected. Most practice nurses seemed unaware of the growth and development elements of clinical supervision. One third of respondents were very vociferous and saw clinical supervision as a threat, the word ‘supervision’ being interpreted as introducing hierarchical management by stealth.Conclusions: There is support that Clinical Supervision has the potential to develop nurses' clinical effectiveness and contribute to clinical governance. It also appears that practice nurses, who work in comparative professional isolation from other nurses, have much to gain personally and professionally from the supportive elements of this initiative. However, this study highlights values and organizational issues that must be considered before implementing this initiative in this particular nursing group.     

Saccharomyces boulardii CNCM I-745 in different clinical conditions

Introduction: Saccharomyces boulardii is a well-known probiotic worldwide, and there are numerous studies including experimental and clinical trials in children and adults by the use of S. boulardii.

Areas covered: The objective of the present report is to provide an update on the evidence for the efficacy of S. boulardii CNCM I-745 in different clinical conditions. Saccharomyces boulardii is one of the best-studied probiotics in acute gastroenteritis (AGE) and is shown to be safe and to reduce the duration of diarrhea and hospitalization by about 1 day. Saccharomyces boulardii is one of the recommended probiotics for AGE in children by European Society of Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Saccharomyces boulardii is also a recommended probiotic for the prevention of antibiotic-associated diarrhea (AAD), and a recent study showed promising results for the treatment of AAD in children. There is insufficient evidence to recommend the long-term use of S. boulardii in patients with irritable bowel syndrome. Although some clinical studies showed positive effects of S. boulardii on inflammation, there is no clinical evidence that S. boulardii is useful in inflammatory bowel disease. Saccharomyces boulardii could be used in patients needing Helicobacter pylori eradication because the S. boulardii improves compliance, decreases the side effects and moderately increases the eradication rate. There are new promising results (improving feeding tolerance, shorten the course of hyperbilirubinemia), but we do still not recommend the routine use of S. boulardii in newborns.

Expert opinion: Saccharomyces boulardii CNCM I-745 is a good example for the statement that each probiotic needs to be taxonomically characterized and its efficacy and safety should be documented individually in different clinical settings.     

CT assessment of abdominal hemorrhage in coagulopathic patients: impact on clinical management

Background: To assess how computed tomography (CT) affected clinical management in coagulopathic patients with suspected spontaneous abdominal hemorrhage. Methods: Fifty-four patients with coagulopathy underwent CT for possible abdominal hemorrhage. Medical records were reviewed retrospectively for pre-CT management strategy, degree of clinical suspicion for abdominal hemorrhage, CT findings, and post-CT management strategy. Results: Abdominopelvic CT demonstrated hemorrhage in 31/54 (57%) of patients; 20/54 (37%) of patients had retroperitoneal hemorrhage, 2/54 (4%) had hemoperitoneum, and 9/54 (17%) had hemorrhage confined to the thigh, groin, and/or abdominal wall. CT directly affected clinical management in 28/54 (54%) cases; 17/31 (55%) CT scans that were positive for hemorrhage had a clinical impact versus 11/23 (48%) negative CT scans. This difference was not statistically significant (p= 0.61). CT scans with a higher pretest suspicion for abdominal hemorrhage were more likely to have hemorrhage detected (p= 0.0046) but not more likely to have a clinical impact (p= 0.73). Conclusions: CT to assess for abdominal hemorrhage had a direct impact on clinical management in about one-half of coagulopathic patients. Positive and negative CT studies were equally likely to affect management. Received: 24 February 1998/Accepted: 8 April 1998     

Disc displacement without reduction with limited opening: A clinical diagnostic accuracy study

Purpose: The purpose of this study is to explore the diagnostic accuracy and clinical utility of an examination by a physical therapist using a clinical patient population for diagnosing a specific sub-type of disc displacement (DDWoR wLO) compared to the imaged disc position. Methods: Data from 46 patients with a clinical diagnosis of DDWoR wLO (92 clinical examinations and MRI records) were collected. Clinical diagnosis was made based on predefined diagnostic criteria, and the MRI diagnosis was made based on the MRI radiology report obtained from the dental provider. A McNemar test was used to determine whether the outcomes of the clinical and MRI diagnoses differed significantly, and sensitivity, specificity, likelihood ratios, predicative values, 95% confidence intervals, and the overall diagnostic accuracy were computed. Results: There was high sensitivity (85%), moderate but unacceptable specificity (73%), and acceptable overall diagnostic accuracy (80%) for using predefined criteria in the diagnosis of DDWoR wLO. The likelihood ratios and predictive values supported the clinical utility of the criteria used for diagnosing DDWoR wLO. Conclusion: This is the first study to characterize diagnostic accuracy by a physical therapist of a specific sub-type of TMD in a clinical patient population rather than a research based population. The results suggest that while sensitivity and the overall diagnostic accuracy were acceptable, specificity was lower than acceptable and these findings are discussed in relation to clinical utility of using diagnostic criteria in a clinical setting against a gold standard of MRI.     

Adipose tissue-derived stem cells in clinical applications

Introduction: In the past decade human adipose tissue has been identified as a source of multipotent stem cells. Adipose tissue derived stem cells (ASCs) are characterised by immunosuppressive properties and low immunogenicity. Therefore, they can be used in regenerative medicine, as well as applied to induce graft tolerance or prevent autoimmunity. ASCs can be easily harvested with low morbidity, which is their main advantage over mesenchymal stem cells (MSCs) derived from other sources.

Areas covered: The review focuses on reported clinical applications of ASCs and discusses technical approaches of their isolation and processing. The differences in phenotype and differentiation preferences between ASCs and other MSCs that may affect the choice of a particular cell type for the future therapy are also described.

Expert opinion: ASCs seem to be the perfect tool for regenerative medicine and immunosuppressive cellular therapies. Nevertheless, there are some tasks that should be addressed by the future studies: i) ASCs require better characterisation; a set of markers determining ASCs should be clearly defined; ii) there is need for more studies on safety of reconstructive therapies with ASCs in cancer patients (e.g., after mastectomy); iii) release criteria should be determined for freshly isolated and ex vivo expanded ASCs designed for clinical applications.     

Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study

Objective: To evaluate the incidence, clinical features, and prognosis of pulmonary complications associated with toxic epidermal necrolysis Design: Prospective study. Setting: Dermatology intensive care unit in Mondor Hospital, France. Patients: 41 consecutive patients. Interventions: On admission, then daily, respiratory evaluation was based on clinical examination, chest X-ray, and arterial blood gas analysis. When clinical symptoms, X-ray abnormalities, or hypoxemia [partial pressure of oxygen (PO₂) < 80 mm Hg] were present, fiberoptic bronchoscopy was performed. Results: 10 patients presented early manifestations: dyspnea (n = 10), bronchial hypersecretion (n = 7), marked hypoxemia (n = 10) (PO₂ = 59 ± 8 mm Hg). Chest X-ray was normal (n = 8) or showed interstitial infiltrates (n = 2). In these 10 patients, fiberoptic bronchoscopy demonstrated sloughing of bronchial epithelium in proximal airways. Delayed pulmonary complications occurred in 6 of these 10 patients from day 7 to day 15: pulmonary edema (n = 2), atelectasis (n = 1), bacterial pneumonitis (n = 4). Mechanical ventilation was required in 9 patients. A fatal outcome occurred in 7 patients. Seven patients did not develop early pulmonary manifestations (PO₂ on admission 87 ± 6 mm Hg) but only delayed pulmonary symptoms related to atelectasis (n = 1), pulmonary edema (n = 4), and bacterial pneumonitis (n = 3); bronchial epithelial detachment was not observed. None of them required mechanical ventilation and all recovered with appropriate therapy. Conclusions:“Specific” involvement of bronchial epithelium was noted in 27 % of cases and must be suspected when dyspnea, bronchial hypersecretion, normal chest X-ray, and marked hypoxemia are present during the early stages of toxic epidermal necrosis. Bronchial injury seems to indicate a poor prognosis, as mechanical ventilation was required for most of these patients and was associated with a high mortality. Received: 3 June 1997 Accepted: 18 October 1997     

Assessment of spasticity after stroke using clinical measures: a systematic review

Abstract

Purpose: To identify and appraise the literature on clinical measures of spasticity that has been investigated in people after stroke. Methods: The literature search involved four databases (PubMed, CINAHL, Embase and The Cochrane Library) up to February 2014. The selected studies included those that aimed to measure spasticity using a clinical assessment tool among adult patients post-stroke. Two independent raters reviewed the included articles using a critical appraisal scale and a structured data extraction form. Results: A total of 40 studies examining 15 spasticity assessment tools in patients post-stroke were reviewed. None of the reviewed measurement tools demonstrated satisfactory results for all psychometric properties evaluated, and the majority lacked evidence concerning validity and absolute reliability. Conclusion: This systematic review found limited evidence to support the use of most of clinical measures of spasticity for people post-stroke. Future research examining the application and psychometric properties of these measures is warranted.

• Implications for Rehabilitation

• There is a need for objective clinical tools for measuring spasticity that are clinically feasible and easily interpreted by clinicians.

• This review identified various clinical measures of spasticity that have been investigated in people after stroke.

• Insufficient evidence of psychometric properties precludes recommending one tool over the others.

• Future research should focus on investigating the psychometric properties of clinical measures of spasticity.

     

Segmental chronic cholecystitis: sonographic findings and clinical manifestations

Background: In chronic cholecystitis, the gallbladder (GB) wall is usually evenly involved, whereas marked segmental thickening of the GB wall (segmental cholecystitis) seldom is reported. We wanted to define its clinical manifestations and sonographic (US) findings. Methods: We reviewed the clinical and US data of 13 cases and compared these results with those of 30 patients with chronic cholecystitis with evenly thickened GB walls (usual-cholecystitis group). Results: (a) All cases of segmental cholecystitis showed the portion distal to the kinking to be markedly thickened. (b) The thickened portion corresponded to the fundus in three cases, the body and fundus in seven cases, and the fundus, body, and infundibulum in three cases; and the thickened distal portion contained many stones in 11 cases. (c) There was no difference in the maximal diameters of the GB walls between the segmental-cholecystitis group and the usual-cholecystitis group. However, there was a significant difference in the minimal diameters of the GB walls between groups. Conclusion: Knowledge of the US findings and clinical presentations of segmental cholecystitis can help in the development of appropriate diagnostic and therapeutic strategies. Received: 22 February 2001/Accepted: 21 March 2001     

Using simulation pedagogy to teach clinical education skills: A randomized trial

Introduction: Supervision of students is a key role of senior physiotherapy clinicians in teaching hospitals. The objective of this study was to test the effect of simulated learning environments (SLE) on educators’ self-efficacy in student supervision skills. Methods: A pilot prospective randomized controlled trial with concealed allocation was conducted. Clinical educators were randomized to intervention (SLE) or control groups. SLE participants completed two 3-hour workshops, which included simulated clinical teaching scenarios, and facilitated debrief. Standard Education (StEd) participants completed two online learning modules. Change in educator clinical supervision self-efficacy (SE) and student perceptions of supervisor skill were calculated. Between-group comparisons of SE change scores were analyzed with independent t-tests to account for potential baseline differences in education experience. Results: Eighteen educators (n = 18) were recruited (SLE [n = 10], StEd [n = 8]). Significant improvements in SE change scores were seen in SLE participants compared to control participants in three domains of self-efficacy: (1) talking to students about supervision and learning styles (p = 0.01); (2) adapting teaching styles for students’ individual needs (p = 0.02); and (3) identifying strategies for future practice while supervising students (p = 0.02). Conclusions: This is the first study investigating SLE for teaching skills of clinical education. SLE improved educators’ self-efficacy in three domains of clinical education. Sample size limited the interpretation of student ratings of educator supervision skills. Future studies using SLE would benefit from future large multicenter trials evaluating its effect on educators’ teaching skills, student learning outcomes, and subsequent effects on patient care and health outcomes.     

The evolution of biomarkers in rheumatoid arthritis: From clinical research to clinical care

Background: Treatment efficacy in rheumatoid arthritis (RA) has been measured by clinical response, gross radiological results and some biochemical markers. With the new biologic treatments, markers for disease development, progress, severity and therapy response have evolved. Objectives: This review focuses on a selection of current markers and the need for better markers for determining RA treatment susceptibility and success. Methods: A review of the literature was conducted and expert opinions expressed. Results/conclusion: Current biomarkers mainly focus on disease activity and severity. Biomarkers for treatment response and susceptibility that help clinicians make initial treatment decisions are lacking or insufficient, yet required for optimal control of RA. A combination of biomarkers is necessary to classify a complex immune disease, such as RA.     

Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair

ABSTRACT

Introduction: Articular cartilage is renowned for its poor intrinsic capacity for repair. Current treatments for osteoarthritis are limited in their ability to reliably restore the native articular cartilage structure and function. Mesenchymal stem cells (MSCs) present an attractive treatment option for articular cartilage repair, with a recent expansion of clinical trials investigating their use in patients.

Areas covered: This paper provides a current overview of the clinical evidence on the use of MSCs in articular cartilage repair.

Expert opinion: The article demonstrates robust clinical evidence that MSCs have significant potential for the regeneration of hyaline articular cartilage in patients. The majority of clinical trials to date have yielded significantly positive results with minimal adverse effects. However the clinical research is still in its infancy. The optimum MSC source, cell concentrations, implantation technique, scaffold, growth factors and rehabilitation protocol for clinical use are yet to be identified. A larger number of randomised control trials are required to objectively compare the clinical efficacy and long-term safety of the various techniques. As the clinical research continues to evolve and address these challenges, it is likely that MSCs may become integrated into routine clinical practice in the near future.     

Proximal small bowel intussusceptions in adults: CT appearance and clinical significance

Background: According to the clinical literature, intestinal intussusception in adults is rare, is associated with a pathologic lead point, and is usually treated surgically. Nonobstructing small bowel intussusception has been reported as a transient finding on computed tomographic (CT) studies.Methods: We evaluated the radiographic and clinical findings in 24 patients who were found to have 26 proximal small bowel intussusceptions on abdominal CT scans performed for a variety of indications.Results: Twenty patients with intussusceptions had no evidence of small bowel obstruction. The transient and clinically insignificant nature of 22 intussusceptions in these 20 patients was proven radiologically (n = 14), surgically (n = 1), or by clinical follow-up (n = 7). These patients demonstrated a bowel-within-bowel pattern on multiple contiguous images and absence of strangulation or intestinal dilatation. No lead points were demonstrated in these patients. Three other patients had symptoms of low-grade small bowel obstruction and were treated conservatively. Extensive follow-up investigations showed no recurrence of intussusception or a lead point. One patient had high-grade obstructive intussusception with intestinal ischemia and required surgical resection of necrotic bowel.Conclusions: Proximal small bowel intussusceptions are likely to be transient and nonobstructive and unlikely to have a significant lead point.     

Differences in clinical presentation of pulmonary embolism in women and men

Summary. Background: The risk of recurrence of pulmonary embolism (PE) is higher in men than in women. Differences in clinical presentation of deep vein thrombosis (DVT) have been reported between the two genders but comparative data on PE are lacking. Objectives:  To compare clinical characteristics between women and men with suspected and confirmed PE and their impact on clinical probability prediction scores and on diagnostic work‐up of PE, and to assess whether differences at presentation could account for the increased recurrence rate in men. Methods:  Combined data from three prospective cohort studies including a total of 3414 outpatients with suspected PE were analyzed retrospectively. Clinical characteristics, pretest probability of PE, diagnostic yield of non‐invasive tests and VTE recurrence rate were compared between genders. Results:  The overall prevalence of PE was similar among women and men (22.3% vs. 23.1%; P = 0.55). The clinical probability prediction scores (Geneva score and Wells score) performed equally well in both genders. A non‐invasive diagnostic work‐up was possible more often in men than in women. The proportion of PE‐associated proximal DVT was higher in men than in women (43% vs. 33%; P = 0.009). VTE recurrence rate was also higher in men than women with PE (5.0% vs. 2.3%; P = 0.045). Conclusion:  In spite of some differences in the clinical presentation of PE between women and men, clinical probability prediction scores perform equally in both genders. A higher prevalence of PE‐associated proximal DVT in men could possibly indicate greater severity of PE episodes and partly account for the higher VTE recurrence rate in men.     

From lab to bedside: emerging clinical applications of thymosin α1

Background: Thymosin α₁ (Tα₁), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Tα₁ is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Tα₁ is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. Objective/methods: Novel applications and other recently completed trials point to much broader clinical applications of Tα₁ in the treatment of life-threatening and chronic diseases, and are the subject of this review. Result/conclusions: The most recent reports of clinical trials with Tα₁ are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection agent in patients undergoing chemotherapy.