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Conservative treatment for whiplash.

BACKGROUND: Many treatments are available for whiplash-patients, but to date, no evidence exists for their effectiveness. OBJECTIVES: The objective of this systematic review was to assess the efficacy of conservative treatment in patients with whiplash-injuries (rated as Whiplash-Associated Disorders [WAD] I or II). SEARCH STRATEGY: A computerized literature search of Medline, Embase, Cinahl, Psychlit and the Cochrane Controlled Trial Register through June 1998 was carried out. We also screened reference lists of publications of identified randomized trials and relevant systematic reviews. SELECTION CRITERIA: Studies were selected for inclusion if they fit the following criteria: design was a (randomized) clinical trial (RCT); all patients had suffered a whiplash-injury; the type of intervention was a conservative one; pain, global perceived effect, or participation in daily activities was used as one of the outcome measures; and the publication was written in English, French, German or Dutch. DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was independently assessed by two reviewers using the Maastricht-Amsterdam list. Three quality scores were calculated using this criteria list: the Overall methodological Quality Score, the Internal Validity Score and the Delphi Quality Score. The conclusion of the review was based on articles that scored a quality score of at least 50 percent of the maximum available score on two out of three quality scores. MAIN RESULTS: Eleven studies met the inclusion criteria. A broad variety of conservative interventions were evaluated, and only one study was performed in chronic whiplash patients. Only three studies satisfied at least 50 percent on two out of three quality scores indicating poor overall methodological quality. A high rank correlation was observed among the three methods of quality. Because of the heterogeneity of patient selection, interventions and outcome measures, no statistical pooling was performed. This review indicates that active treatments show a beneficial effect on at least one of the primary outcome measures, preferably pain. REVIEWER'S CONCLUSIONS: It appears that "Rest makes rusty." In other words, rest and immobilization using collars are not recommended for the treatment of whiplash, while active interventions, such as advice to 'maintain usual activities' might be effective in whiplash-patients. Nevertheless, caution is needed when attempting to draw conclusions regarding the efficacy of conservative treatments in whiplash-patients, because of the paucity of high-quality studies. No conclusions can be drawn about the most effective therapy for chronic whiplash-patients because only one low quality trial was identified.

Activities of Daily Living↗

Conservative treatments for whiplash.

BACKGROUND: Our previous review examining conservative treatments for whiplash was published in 2001. Since then, new trials have been published.Whiplash-associated disorders (WAD) can be classified by the severity of signs and symptoms: WAD Grade 0 indicates no complaints or physical signs; Grade 1 indicates neck complaints but no physical signs; Grade 2 indicates neck complaints and musculoskeletal signs; Grades 3 and 4 indicate neck complaints and neurological signs or fracture/dislocation, respectively. OBJECTIVES: To assess the effectiveness of conservative treatment in patients with WAD Grades 1 or 2. SEARCH STRATEGY: We completed a computerised search of CENTRAL, MEDLINE, EMBASE, CINAHL, PsycLIT, and PEDro, to April 2003. We also screened references of identified trials and relevant systematic reviews. SELECTION CRITERIA: Studies were selected if they were a (randomised) clinical trial, examined patients with a WAD, examined conservative treatments, measured one of: pain, global perceived effect or participation in daily activities, and were published in English, French, German or Dutch. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality using the Delphi list and extracted the data using standardised forms. Because the population, interventions and outcome measures were heterogeneous, we used a rating system with levels of evidence rather than statistical pooling for the analysis. Clinically relevant improvement was defined as a 15% improvement relative to a control. A pre-planned stratified analysis was performed in three groups. MAIN RESULTS: We found four new studies since the previous review, resulting in 15 studies that met the inclusion criteria. Just one study evaluated patients with chronic WAD. Only three studies satisfied one of our criteria of high quality, indicating overall a poor methodological quality. The broad array of conservative interventions were divided into passive and active interventions and were compared with each other, no treatment, or a placebo group. There was limited evidence that both passive and active interventions seemed to be more effective than no treatment. Contrary to our earlier review, we found conflicting evidence about the effectiveness of active interventions compared to passive ones. All but one study mentioned positive results, but the actual data of the high quality studies were conflicting. REVIEWER'S CONCLUSIONS: When looking at the actual data presented in the current included trials, our conclusion from the previous version of this review, that 'rest makes rusty', can no longer be justified. There is a trend suggesting that active interventions are more effective than passive ones, but no clear conclusion can be drawn. We can draw no conclusion about the most effective therapy for patients with chronic WAD, because only one low quality trial was found.

Chronic Disease↗

Ergonomic and physiotherapeutic interventions for treating upper extremity work related disorders in adults.

BACKGROUND: Conservative interventions such as physiotherapy and ergonomic adjustments play a major part in the treatment of most work-related musculoskeletal disorders (WRMD). OBJECTIVES: The objective of this systematic review is to determine whether conservative interventions have a significant impact on short and long-term outcomes for upper extremity WRMD in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (January 2002) and Cochrane Rehabilitation and Related Therapies Field specialised register (January 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), PubMed (1966 to November 2001), EMBASE (1988 to November 2001), and CINAHL (1982 to November 2001). We also searched the Physiotherapy Index (1988 to November 2001) and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA: Only randomised controlled trials and concurrent controlled trials studying conservative interventions for adults suffering from upper extremity WRMD were included. Conservative interventions may include exercises, relaxation, physical applications, biofeedback, myofeedback and work place adjustments. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials from the search yield and assessed the clinical relevance and methodological quality using the Delphi list. In the event of clinical heterogeneity or lack of data we used a rating system to assess levels of evidence. MAIN RESULTS: We included 15 trials involving 925 people. Twelve trials included people with chronic non-specific neck or shoulder complaints, or non-specific upper extremity disorders. Over 20 interventions were evaluated; seven main subgroups of interventions could be determined: exercises, manual therapy, massage, ergonomics, multidisciplinary treatment, energised splint and individual treatment versus group therapy. Overall, the quality of the studies appeared to be poor. In 10 studies a form of exercise was evaluated, and there is limited evidence about the effectiveness of exercises only when compared to no treatment. Concerning manual therapy (1 study), massage (4 studies), multidisciplinary treatment (1 study) and energised splint (1 study) no conclusions can be drawn. Limited evidence is found concerning the effectiveness of specific keyboards for patients with carpal tunnel syndrome. REVIEWER'S CONCLUSIONS: This review shows limited evidence for the effectiveness of keyboards with an alternative force-displacement of the keys or an alternative geometry, and limited evidence for the effectiveness of individual exercises. The benefit of expensive ergonomic interventions (such as new chairs, new desks etc) in the workplace is not clearly demonstrated.

Adult↗

Ergonomic and physiotherapeutic interventions for treating work-related complaints of the arm, neck or shoulder in adults.

BACKGROUND: Conservative interventions such as physiotherapy and ergonomic adjustments (such as keyboard adjustments or ergonomic advice) play a major role in the treatment of most work-related complaints of the arm, neck or shoulder (CANS). OBJECTIVES: This systematic review aims to determine whether conservative interventions have a significant impact on outcomes for work-related CANS in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2005) and Cochrane Rehabilitation and Related Therapies Field Specialised Register (March 2005), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2005), PubMed, EMBASE, CINAHL, AMED and reference lists of articles. The date of the last search was March 2005. No language restrictions were applied. SELECTION CRITERIA: We included randomised and non-randomised controlled trials studying conservative interventions (e.g. exercises, relaxation, physical applications, biofeedback, myofeedback and work-place adjustments) for adults suffering CANS. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials from the search yield, assessed the methodological quality using the Delphi list, and extracted relevant data. We pooled data or, in the event of clinical heterogeneity or lack of data, we used a rating system to assess levels of evidence. MAIN RESULTS: For this update we included six additional studies; 21 trials in total. Seventeen trials included people with chronic non-specific neck or shoulder complaints, or non-specific upper extremity disorders. Over 25 interventions were evaluated; five main subgroups of interventions could be determined: exercises, manual therapy, massage, ergonomics, and energised splint. Overall, the quality of the studies was poor. In 14 studies a form of exercise was evaluated, and contrary to the previous review we now found limited evidence about the effectiveness of exercises when compared to massage and conflicting evidence when exercises are compared to no treatment. In this update there is limited evidence for adding breaks during computer work; massage as add-on treatment on manual therapy, manual therapy as add-on treatment on exercises; and some keyboard designs when compared to other keyboards or placebo in participants with carpal tunnel syndrome. AUTHORS' CONCLUSIONS: There is limited evidence for the effectiveness of keyboards with an alternative force-displacement of the keys or an alternative geometry, and limited evidence for the effectiveness of exercises compared to massage; breaks during computer work compared to no breaks; massage as an add-on treatment to manual therapy; and manual therapy as an add-on treatment to exercises.

Adult↗

Braces and orthoses for treating osteoarthritis of the knee.

BACKGROUND: Patients with osteoarthritis of the knee can be treated with a brace or orthosis (shoe insole). The main purpose of these aids is to reduce pain, improve physical function and, possibly, to slow disease progression. OBJECTIVES: To assess the effectiveness of a brace or orthosis in the treatment of osteoarthritis of the knee. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE (Current contents, Health STAR) up to October 2002. The reference lists of the publications in the identified trials were also screened. SELECTION CRITERIA: Extracted studies were included in the final analysis if they met the pre-defined inclusion criteria: 1) a randomised controlled clinical trial or a controlled clinical trial, 2) all patients had osteoarthritis of the knee, 3) the intervention in one of the studied groups was a brace or an orthosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials and assessed the methodological quality using the Delphi-list and one additional question about care programs. Three reviewers independently extracted the data on the intervention, type of outcome measures, follow-up, loss to follow-up, and results, using a pre-tested standardized form. Study authors were contacted for additional information. MAIN RESULTS: Four trials involving a total of 444 people were included in this review. One study investigated a knee brace and three studies examined different types of orthoses for medial compartment osteoarthritis of the knee. Two studies were of high methodological quality while the other two studies were low. Notably, the randomisation and the blinding procedures were either insufficient or not described. The follow-up period (six weeks to six months) was too short to demonstrate long-term results. Pooling was difficult primarily due to the heterogeneity of the data and the way the information was presented. The pain, stiffness and physical function (WOMAC and MACTAR) scores of a brace group showed greater improvement at six months compared with a neoprene sleeve group, which showed greater improvement compared with a control group. The numbers of days of non-steroidal anti-inflammatory drug (NSAID) intake decreased significantly (relative percentage difference 23.9%) compared with baseline in a group with laterally wedged insoles,and remained unchanged in the neutrally wedged group. Patient compliance with the laterally wedged insole was significantly better compared with the neutrally wedged insole. In one study, the Visual Analogue Pain (VAS) pain score was significantly decreased from baseline in a strapped insole group (RPD - 24%), but not in the traditional lateral wedge group, but this strapped insole showed more adverse effects (popliteal pain, low back pain, and foot sole pain) compared with the traditional lateral wedge insole. Pain during bed rest, after getting up, after getting up from seated position and walking distance was significantly improved in a subtalar strapped group compared with baseline, and no improvement was found in a sock type group. No studies were found that assessed the effectiveness of a brace or orthosis to treat lateral compartment osteoarthritis or general osteoarthritis of the knee, or that compared a knee brace with a wedge insole, or that compared a brace or orthosis with operative treatment. AUTHORS' CONCLUSIONS: Based on one brace study we conclude there is limited evidence that: a brace has additional beneficial effect (WOMAC, MACTAR, function tests) for knee osteoarthritis compared with medical treatment alone.(Silver) a sleeve has additional beneficial effect (WOMAC, function tests) for knee osteoarthritis compared with medical treatment alone.(Silver) a brace is more effective (WOMAC, function tests) than a neoprene sleeve.(Silver) Based on 3 orthoses studies, of which 2 were high quality, (n=2) we conclude there is limited evidence that: a laterally wedged insole decreases NSAID intake compared with a neutral insole. (Silver) patient compliance is better in the laterally wedged insole compared with a neutral insole. (Silver) a strapped insole has more adverse effects than a lateral wedge insole. (Silver).

Braces↗

The AIMS2-SF: a short form of the Arthritis Impact Measurement Scales 2. French Quality of Life in Rheumatology Group.

OBJECTIVE: To develop a short form of the Arthritis Impact Measurement Scales 2 (AIMS2) questionnaire, preserving content validity as the priority criterion. METHODS: A 2-step reduction procedure was used: 1) Delphi technique, with 1 panel of patients and 1 panel of experts each selecting 1 set of items independently; and 2) nominal group technique, where members of both panels reached consensus on the final selection of items, using information derived from item analysis. Psychometric properties of the AIMS2-Short Form (AIMS2-SF) and AIMS2 were compared using data from a cohort of 127 rheumatoid arthritis patients who completed the AIMS2 twice prior to the initiation of methotrexate (MTX) treatment and 3 months post-initiation of MTX treatment. RESULTS: The 2 panels reached consensus on a 26-item AIMS2-SF (54.4% reduction from the AIMS2). Factor analysis showed preservation of the 5-component structure. Convergent validity (Physical and Symptom components with clinical variables: r = 0.24-0.59), test-retest reproducibility (intraclass correlation coefficient >0.7), and sensitivity to change at 3 months (standardized response mean 0.36-0.8, except Social Interaction component [0.08]) were very close to the values for the original AIMS2. CONCLUSION: The AIMS2-SF is a shorter version of the AIMS2 (i.e., available in 2-page format) and has psychometric properties similar to those of the AIMS2.

Activities of Daily Living↗

National Stroke Association guidelines for the management of transient ischemic attacks.

OBJECTIVE: Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks. METHODS: Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest. RESULTS: Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management. INTERPRETATION: The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

Health Planning Guidelines↗

Studies on the fetal development of the gubernaculum in cetacea.

BACKGROUND: Adult cetacean males, like non-mammalian vertebrates and other testicond mammals, have intra-abdominal testes. There is no evidence of a processus vaginalis in them. Testicondia in cetaceans is considered secondary as they are judged, evolutionarily, the descendants of terrestrial mammals (ungulates) with testis descent. A possible argument in support of the latter contention would be that cetacean fetuses develop gubernacula which are the primordia of the processus vaginalis and other structures associated with testis descent in other placental mammals. The present study intended to analyse cetacean fetuses in this respect. METHODS: Serial sections of 25 fetuses (total body length between 39.5 and 160 mm) of 4 cetacean species (Delphinus delphis, Phocoena phocoena, Eschrichtius robustus, Physeter catodon) were examined with special attention to the presence or absence of structures homologous to the gubernaculum of other placental mammals (rats and humans). RESULTS: Gubernacular primordia were observed in fetuses from about the time of onset of sexual differentiation. Their shape and anatomical relationship with the surrounding structures were similar as those in mammals with testis descent. The gubernaculum in males developed into a large mass of dense connective tissue in the ventral-caudal abdominal region at the site of the insertion of the mesonephric inguinal ligament and associated to the tip of the internal abdominal oblique muscle. No (or only very little) development of a processus vaginalis was noticed. CONCLUSIONS: The results demonstrate initial emergence of mammalian-like gubernacular primordia in cetacean fetuses without their further development to elaborate structures required for testis descent. The findings support the view that cetaceans are secondarily testicond. It is suggested that (1) absence of the pelvic girdle together with (2) the development of structures in and beyond the caudal abdominal region, particularly the caudal hypaxial musculature, precludes the outgrowth, into caudal direction, of hollow organs (such as the processus vaginalis) from the abdominal cavity.

Animals↗

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗

Violation of the intent-to-treat principle and rate of missing data in superiority trials assessing structural outcomes in rheumatic diseases.

OBJECTIVE: To evaluate the methodologic quality of and identify methodologic issues in superiority trials assessing structural outcomes in rheumatic diseases. METHODS: We searched Medline and the Cochrane Central Register of Controlled Trials for reports of randomized controlled trials assessing structural outcomes in osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) published between January 1994 and December 2003 in high-impact factor general medical and specialty journals. One reader extracted data (quality assessment, intent-to-treat analysis [ITT analysis], rate of missing data, and methods of handling missing data), using a standardized form. RESULTS: A total of 81 reports were included in the analysis (37 on OP, 34 on RA, and 10 on OA). The mean +/- SD methodologic quality scores on the Jadad scale (possible range 0-5) and the Delphi list (possible range 0-9) were 2.9 +/- 1.2 and 6.4 +/- 1.3, respectively. Although it was reported in 54 articles (66.7%) that the analysis was done on an ITT basis, full ITT analysis was performed in only 6 of the studies (7.4%), modified ITT analysis in 11 (13.6%), and case-complete analysis in 48 (59.3%); the analysis was unclear in 16 articles (19.8%). The rate of missing data on structural outcomes could be determined in only 63 articles (77.8%) and was >20% in approximately one-third of these reports. Methods for handling missing data on structural outcomes were described in 19 articles (23.5%) and were, in general, inappropriate. CONCLUSION: Lack of ITT analysis and a high rate of missing data in superiority trials assessing structural outcomes may bias results from such trials. Our recommendations for improving these shortcomings may help researchers plan, analyze, and report the results of such trials.

Arthritis, Rheumatoid↗

Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen.

OBJECTIVE: To develop and validate a musculoskeletal screening examination applicable to school-age children based on the adult Gait, Arms, Legs, Spine (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children attending pediatric rheumatology clinics and was compared with an examination conducted, on the same day, by a pediatric rheumatologist who classified children as having abnormal or normal joints. Adult GALS was tested for validity compared with the pediatric rheumatologist's assessment and deficiencies in adult GALS were identified. Experts proposed amendments to adult GALS, achieving consensus by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was tested (methodology identical to the testing of adult GALS) in an additional group of children. RESULTS: Adult GALS was tested in 50 children (median age 11 years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult GALS missed important abnormalities in 18% of children, mostly at the ankle, foot, and temporomandibular joints. The pGALS was tested in 65 children (median age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%) and specificity (98-100%) at all joints, with high acceptability scored by child and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3 minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent validity, is quick to perform, and is acceptable to school-age children and parents/guardians. We propose that pGALS be incorporated into undergraduate and postgraduate medical training to improve pediatric musculoskeletal clinical skills and facilitate diagnosis and referral to specialists.

Adolescent↗

Conformational analysis of endothelin-1: effects of solvation free energy.

In order to investigate conformational preferences of the 21-residue peptide hormone endothelin-1 (ET-1), an extensive conformational search was carried out in vacuo using a combination of high temperature molecular dynamics/annealing and a Monte Carlo/minimization search in torsion angle space. Fully minimized conformations from the search were grouped into families using a clustering technique based on rms fitting over the Cartesian coordinates of the atoms of the peptide backbone of the ring region. A wide range of local energy mining were identified even though two disulfide bridges (Cys1-Cys15 and Cys3-Cys11) constrain the structure of the peptide. Low energy conformers of ET-1 as a nonionized species in vacuo are stabilized by intramolecular interaction of the ring region (residues 1-15) with the tail (residues 16-21). Strained conformations for individual residues are observed. Conformational similarity to protein loops is established by matching to protein crystal structures. In order to assess the influence of aqueous environment on conformational preference, the electrostatic contribution to the solvation energy was calculated for ET-1 as a fully ionized species (Asp8, Lys9, Glu10, Asp18, N- and C-terminus) using a continuum electrostatics model (DelPhi) for each of the conformers generated in vacuo, and the total solvation free energy was estimated by adding a hydrophobic contribution proportional to solvent accessible surface area. Solvation dramatically alters the relative energetics of ET-1 conformers from that calculated in vacuo. Conformers of ET-1 favored by the electrostatic solvation energy in water include conformers with helical secondary structure in the region of residues 9-15. Perhaps of most importance, it was demonstrated that the contribution to solvation by an individual charge depends not only on its solvent accessibility but on the proximity of other charges, i.e., it is a cooperative effect. This was shown by the calculation of electrostatic solvation energy as a function of conformation with individual charges systematically turned "on" and "off". The cooperative effect of multiple charges on solvation demonstrated in this manner calls into question models that relate solvation energy simply to solvent accessibility by atom or residue alone.

Amino Acid Sequence↗

Antiplatelet therapy in the prevention of ischemic vascular events: literature review and evidence-based guidelines for drug selection.

BACKGROUND: New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in patients with atherosclerotic vascular disease have been performed. HYPOTHESIS: An updated systematic review and evidence-based guidelines for the appropriate selection of antiplatelet drugs may be beneficial to physicians and healthcare organizations attempting to create or update current clinical practice guidelines or clinical pathways aimed at caring for these patients. METHODS: (1) A systematic review of the recent literature on the relative efficacy and safety of aspirin, ticlopidine, and clopidogrel was undertaken; (2) an evidence-based, expert panel approach using a modified Delphi technique to create explicit guidelines for prescribing antiplatelet therapy was instituted; and (3) the recommendations of an expert panel were summarized. RESULTS: Consensus guidelines were developed for the utilization of aspirin, ticlopidine, or clopidogrel for the prevention of ischemic events in patients with manifestations of atherosclerotic vascular disease (prior myocardial infarction, prior ischemic stroke, or established peripheral arterial disease) who are at increased risk for recurrent ischemic events. Based on efficacy and safety, clopidogrel was recommended as the drug of choice for patients with established peripheral arterial disease; aspirin or clopidogrel should be considered in patients with prior myocardial infarction (with clopidogrel favored for patients who have had a recurrent event while on aspirin or in whom aspirin is contraindicated); aspirin or clopidogrel should be considered as first-line treatment in patients with prior ischemic (nonhemorrhagic) stroke--however, clopidogrel is the favored drug in patients in whom other antiplatelet drugs are either contraindicated or who have had recurrent events while on therapy. CONCLUSIONS: Myocardial infarction, ischemic stroke, and peripheral arterial disease are all clinical manifestations of the same underlying disease process (atherosclerosis), with thrombus formation on the disrupted atherosclerotic plaque (atherothrombosis) being a common precipitating factor of ischemic events in patients suffering from these disorders. An evidence-based approach was used to develop a practice guideline, based on available published evidence, for the appropriate utilization of antiplatelet agents (aspirin, ticlopidine, or clopidogrel). These guidelines may be of use to multidisciplinary teams wishing to create or update clinical guidelines or clinical pathways which address the care of patients with atherosclerotic vascular disease. New antiplatelet agents such as clopidogrel may be more effective and associated with lower risk of selected adverse effects (such as gastrointestinal distress, gastrointestinal hemorrhage, and neutropenia) than those previously used to prevent thrombus formation in the setting of atherosclerotic arterial disease. Combination antiplatelet therapy is being evaluated as an option for those patients who experience recurrent events on a single antiplatelet agent.

Algorithms↗

Assessing the health care needs of adolescent and young adult cancer patients and survivors.

BACKGROUND: Improvements in cancer outcomes observed for the United States population as a whole are not experienced as such by adolescent and young adult (AYA) patients. The objective of this study was to identify important health and supportive care needs for AYA patients and survivors. METHODS: Forty oncology health professionals and 37 young adults (ages 18 years to 44 years; diagnosed between ages 15 years and 39 years) participated on a modified Delphi panel. Over 3 iterative rounds of mailed surveys, participants identified, rank ordered, and rated the importance of various items. RESULTS: Overall, there was general agreement among health care providers and young adult survivors, with some notable exceptions. Providers and young adult survivors agreed on the relative importance of having adequate health insurance and oncology care that addresses the unique developmental characteristics of this population. Compared with health professionals, young adults ranked the importance of opportunities to meet other young adult survivors at a relatively higher level, and they also ranked those opportunities higher than the importance of support from family and friends. CONCLUSIONS: These findings provide oncology professionals and young adults with insight into the others' values and perspectives. These findings also suggest areas in which to target investments of resources to promote quality health care and appropriate informational and supportive care services and to overcome the deficit in survival improvement that has occurred in young adults and older adolescents with cancer.

Adolescent↗

Attribution for successful relationships between severely disabled adults and personal care attendants.

This study explored the mutual perceptions of a convenience sample of 22 pairs of severely disabled adults and their personal care attendants regarding their definitions of the relationship and causal explanations for the relationship outcome (either success or failure). A semistructured interview and Delphi instrument were used to collect data. Attribution theory was used to shape the study design. The most frequently cited causal explanations for a successful outcome were mutual effort, skill, and commitment of the personal care attendant and disabled employer. The majority of subjects defined their relationship as productive and friendly. The data support previous findings and provide direction for programs to prepare disabled people and personal care attendants for their respective roles.

Adult↗

Rotation of middle ear ossicles during cetacean development.

Cetacean middle ears are unique among mammals in that they have an elongated tympanic membrane, a greatly reduced manubrium mallei, and an incudal crus longum that is shorter than the crus breve. Elongation of the tympanic membrane and reduction of the manubrium is thought to be related to an evolutionary rotation of the incus and malleus out of the plane of the tympanic membrane. We examined if rotation also occurs during ontogeny by comparing the middle ears of two species of dolphins (Delphinus delphis, Stenella attenuata) at different stages of development. We observed that: the incus has the body and crural proportions as in terrestrial mammals early in development; the incudomallear complex rotates approximately 90 degrees following ossification; the tympanic membrane is not elongated until relatively late in development. Therefore, some of the unique characteristics of the cetacean middle ear develop as modifications of an initially terrestrial-like morphology.

Animals↗

Head morphology in perinatal dolphins: a window into phylogeny and ontogeny.

In this paper on the ontogenesis and evolutionary biology of odontocete cetaceans (toothed whales), we investigate the head morphology of three perinatal pantropical spotted dolphins (Stenella attenuata) with the following methods: computer-assisted tomography, magnetic resonance imaging, conventional X-ray imaging, cryo-sectioning as well as gross dissection. Comparison of these anatomical methods reveals that for a complete structural analysis, a combination of modern imaging techniques and conventional morphological methods is needed. In addition to the perinatal dolphins, we include series of microslides of fetal odontocetes (S. attenuata, common dolphin Delphinus delphis, narwhal Monodon monoceros). In contrast to other mammals, newborn cetaceans represent an extremely precocial state of development correlated to the fact that they have to swim and surface immediately after birth. Accordingly, the morphology of the perinatal dolphin head is very similar to that of the adult. Comparison with early fetal stages of dolphins shows that the ontogenetic change from the general mammalian bauplan to cetacean organization was characterized by profound morphological transformations of the relevant organ systems and roughly seems to parallel the phylogenetic transition from terrestrial ancestors to modern odontocetes.

Animals↗

On how the periosteal bone of the delphinid humerus becomes cancellous: ontogeny of a histological specialization.

In cetaceans, the bones of the flippers lack a free medullary cavity and have a cancellous texture, with compact cortices reduced or absent. The present work discusses the ontogenetic basis of these characters in terms of the ontogeny of the structure and textural bone compactness (TBC) of the humeral diaphysis in a growth series of common dolphins (Delphinus delphis). The texture of the primary periosteal deposits is compact; soon after their accretion, the deposits undergo an extensive erosion that turns them into a cancellous tissue. A diffuse endosteal front of resorption expands in parallel with the growth of the cortex and acts as small units scattered within the cortices. Starting soon after birth and continuing throughout the life of the animals, the compactness of the periosteal cortex decreases at both general and local levels. This trend correlates strongly with the increase in size of the diaphyseal section and reflects the fact that relatively more bone is eroded than deposited during growth in the cancellous parts of the cortex. In the broad sense, this is basically an osteoporotic process, which is not identical, however, to senile or disuse osteoporoses.

Animals↗