The broad-spectrum antiemetic effects ETI-385 result from stimulation of 5-HT1A and 5-HT1D receptors.

In the present study, we describe how a nonstoichiometric ratio of the isomers of 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT) produce a broad-spectrum of antiemetic effects in cats and shrews. Determination of the receptor profile of the isomers and testing them separately in cats revealed superior antiemetic effects but severe defensive behavior with the R isomer compared with the S isomer. Differing ratios yielded the best results with the 1:8 (R-S) ratio producing a drug more potent than DPAT and with negligible defensive behavior side effects. Studies with selective 5-HT1D ligands led to the conclusion that this site contributes antiemetic efficacy but is not related to defensive behavior, which is most likely a consequence of 5-HT7 receptor activation. ETI-385 was effective in preventing emetic responses to provocative motion, drugs acting at the chemical trigger zone and cisplatin in both cats and shrews. The results support a clinical trial of this drug for antiemetic effects.

Evidence supporting nutritional interventions for persons in early stage Alzheimer's disease (AD).

The purpose of this paper is to grade research evidence supporting nutritional interventions for persons with early stage dementias and to report the recommendations of a consensus panel. Thirty four studies were reviewed in the areas of dietary restriction, antioxidants, and Mediterranean diet with strong support from epidemiological studies found in all three areas. The body of evidence to support nutritional interventions in the prevention and treatment of AD is growing and has potential as a treatment modality following translational studies.

Extended duration regional analgesia for total knee arthroplasty: a randomised controlled trial comparing five days to three days of continuous adductor canal ropivacaine infusion.

There is a growing body of evidence in favour of continuous adductor canal block (CACB) for total knee arthroplasty. However, there are no studies describing the optimal duration of the infusion. At our institution the usual practice was to stop the infusion on day three. Our hypothesis was that extending the infusion to five days would improve analgesia and quality of recovery. A prospective, non-blinded, randomised trial was undertaken. Patients received a continuous infusion of 0.2% ropivacaine via an adductor canal catheter for either three or five days. Primary outcome was pain while walking during the 24-hour period up to day five (numeric rating scale from 0 to 10). The minimum clinically important difference was set at 1.5 on the numeric rating scale. Secondary outcome measures included quality of recovery, mobility, pain while walking on postoperative day six, Oxford Knee Scores, and complications. Eighty-six patients were recruited with 43 randomised to each group. Seventy-eight were analysed. Median pain scores reported on day five were significantly better in the intervention group (1 versus 3, P=0.003). Furthermore, quality of recovery (QOR-15) scores were significantly better in the intervention group (133.6 versus 123.4, P=0.017). No statistically significant difference between groups was identified for other secondary outcome measures. CACB prolonged to five days provides superior analgesia and a higher quality of recovery on postoperative days four and five compared to a three-day infusion. This benefit did not extend beyond the period of infusion.

MRI and clinical evaluation of collagen-covered autologous chondrocyte implantation (CACI) at two years.

We present our experience with the collagen-covered autologous chondrocyte implantation (CACI) technique. Thirty two implantations were performed in 31 patients. Clinical outcome was measured using the KOOS score and the 6-minute walk test, as well as an MRI scoring protocol (75% of patients had a complete data set for MRI follow-up) to describe the repair tissue generated by CACI. We have also correlated our MRI results with our clinical outcome. To the authors knowledge there are no comparative studies of MRI and clinical outcome following CACI in the current literature. Patients demonstrated an increased walk distance that improved significantly from 3 months to 24 months postoperatively (p<0.05). Analysis of the KOOS results demonstrated a significant (p<0.05) improvement in four of the five subscales from 3 months to 24 months after CACI, with the most substantial gains made in the first 12 months. Patients demonstrated an increased MRI outcome score over time that improved significantly from 3 months to 24 months postoperatively (p<0.05). We observed an 8% incidence of hypertrophic growth following CACI. We report one partial graft failure, defined by clinical, MRI and histological evaluation, at the one year time point. In contrast to the current literature we report no incidence of manipulation under anesthesia (MUA) following CACI. This research demonstrates that autologous chondrocytes implanted under a type I/III collagen patch regenerates a functional infill material, and as a result of this procedure, patients experienced improved knee function and MRI scores. Whilst our results indicated a statistically significant relationship between the MRI and functional outcome following CACI, MRI cannot be used as surrogate measure of functional outcome following CACI, since the degree of association was only low to moderate. That is, functional outcome following CACI cannot be predicted by the morphological MRI assessment of the repair tissue at the post-surgery time points to 24 months.

Operative and non-operative treatment options for dislocation of the hip following total hip arthroplasty.

BACKGROUND: Dislocation following hip replacement is associated with significant morbidity and functional cost. The cause is usually multifactorial. A variety of treatment options are available which can broadly be classified into operative and non-operative. OBJECTIVES: To determine the best methods of treatment of recurrent dislocation following total hip replacement. SEARCH STRATEGY: The following databases were searched until August 2006: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Health Technology Assessment database (HTA), Database of Abstracts of Reviews of Effectiveness (DARE), International Standard Randomised Controlled Trial Number Register (ISRCTN), and MetaRegister of Controlled Trials (mRCT). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing operative and non-operative treatments for recurrent dislocation following total hip replacement. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied the inclusion criteria to identified studies. MAIN RESULTS: Searches identified 269 studies. None fulfilled the inclusion criteria. AUTHORS' CONCLUSIONS: The authors invite researchers to perform RCTs comparing different treatment options for recurrent dislocation of the hip. The heterogeneity of the population and variety of underlying causes would favour a multi-centre study to achieve an adequate sample size.

A comparison of three methods of wound closure following arthroplasty: a prospective, randomised, controlled trial.

We carried out a blinded prospective randomised controlled trial comparing 2-octylcyanoacrylate (OCA), subcuticular suture (monocryl) and skin staples for skin closure following total hip and total knee arthroplasty. We included 102 hip replacements and 85 of the knee.OCA was associated with less wound discharge in the first 24 hours for both the hip and the knee. However, with total knee replacement there was a trend for a more prolonged wound discharge with OCA. With total hip replacement there was no significant difference between the groups for either early or late complications. Closure of the wound with skin staples was significantly faster than with OCA or suture. There was no significant difference in the length of stay in hospital, Hollander wound evaluation score (cosmesis) or patient satisfaction between the groups at six weeks for either hips or knees. We consider that skin staples are the skin closure of choice for both hip and knee replacements.

Compartment syndrome following total knee arthroplasty: a report of seven cases.

Compartment syndrome is a rare complication of total knee arthroplasty that requires early recognition and prompt decompression in order to prevent long-term disability. We have found only one previous case report in the literature. We present a series of seven cases from four hospitals and five surgeons. Six of the cases resulted in the loss of at least one compartment, and one resulted in amputation. Four of the cases resulted in legal action. We suggest that important risk factors contributing to the development of this condition include complex surgery, soft-tissue compromise, previous surgery, and possibly vascular disease. Delay in the diagnosis and hence delay in decompression was common in our series, and in five cases appeared to be related to the use of a postoperative epidural infusion for pain relief. The presence of associated neurological compromise may have also been a significant factor in the delay to diagnosis in two cases.

A constrained acetabular component for recurrent dislocation.

We treated 34 patients with recurrent dislocation of the hip with a constrained acetabular component. Roentgen stereophotogrammetric analysis was performed to assess migration of the prosthesis. The mean clinical follow-up was 3.0 years (2.2 to 4.8) and the radiological follow-up was 2.7 years (2.0 to 4.8). At the latest review six patients had died and none was lost to follow-up. There were four acetabular revisions, three for aseptic loosening and one for deep infection. Another acetabular component was radiologically loose with progressive radiolucent lines in all Gruen zones and was awaiting revision. The overall rate of aseptic loosening was 11.8% (4 of 34). Roentgen stereophotogrammetric analysis in the non-revised components confirmed migration of up to 1.06 mm of translation and 2.32 degrees of rotation at 24 months. There was one case of dislocation and dissociation of the component in the same patient. Of the 34 patients, 33 (97.1%) had no further episodes of dislocation. The constrained acetabular component reported in our study was effective in all but one patient with instability of the hip, but the rate of aseptic loosening was higher than has been reported previously and requires further investigation.

Component alignment and clinical outcome following total knee arthroplasty: a randomised controlled trial comparing an intramedullary alignment system with patient-specific instrumentation.

AIMS: We conducted a randomised controlled trial to assess the accuracy of positioning and alignment of the components in total knee arthroplasty (TKA), comparing those undertaken using standard intramedullary cutting jigs and those with patient-specific instruments (PSI). PATIENTS AND METHODS: There were 64 TKAs in the standard group and 69 in the PSI group. The post-operative hip-knee-ankle (HKA) angle and positioning was investigated using CT scans. Deviation of > 3° from the planned position was regarded as an outlier. The operating time, Oxford Knee Scores (OKS) and Short Form-12 (SF-12) scores were recorded. RESULTS: There were 14 HKA-angle outliers (22%) in the standard group and nine (13%) in the PSI group (p = 0.251). The mean HKA-angle was 0.5° varus in the standard group and 0.2° varus in the PSI group (p = 0.492). The accuracy of alignment in the coronal and axial planes and the proportion of outliers was not different in the two groups. The femoral component was more flexed (p = 0.035) and there were significantly more tibial slope outliers (29% versus 13%) in the PSI group (p = 0.032). Operating time and the median three-month OKS were similar (p = 0.218 and p = 0.472, respectively). Physical and mental SF-12 scores were not significantly different at three months (p = 0.418 and p = 0.267, respectively) or at one year post-operatively (p = 0.114 and p = 0.569). The median one-year Oxford knee score was two points higher in the PSI group (p = 0.049). CONCLUSION: Compared with standard intramedullary jigs, the use of PSI did not significantly reduce the number of outliers or the mean operating time, nor did it clinically improve the accuracy of alignment or the median Oxford Knee Scores. Our data do not support the routine use of PSI when undertaking TKA. Cite this article: Bone Joint J 2016;98-B:1043-9.

Interventions for treating acute Achilles tendon ruptures.

BACKGROUND: There is lack of consensus on the best management of the acute Achilles tendon (TA) rupture. Treatment can be broadly classified into operative (open or percutaneous) and non-operative (cast immobilisation or functional bracing). Post-operative splintage can be with a rigid cast (above or below the knee) or a more mobile functional brace. OBJECTIVES: To identify and summarise the evidence from randomised controlled trials of the effectiveness of different interventions in the treatment of acute Achilles tendon ruptures. SEARCH STRATEGY: We searched multiple databases including the Cochrane Musculoskeletal Injuries Group specialised register (to September 2003), reference lists of articles and contacted trialists. Keywords included Achilles Tendon, Rupture, and Tendon Injuries. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing different treatment regimens for acute Achilles tendon ruptures. DATA COLLECTION AND ANALYSIS: Three reviewers extracted data and independently assessed trial quality by use of a ten-item scale. MAIN RESULTS: Fourteen trials involving 891 patients were included. Several of the studies had poor methodology and inadequate reporting of outcomes. Open operative treatment compared with non-operative treatment (4 trials, 356 patients) was associated with a lower risk of rerupture (relative risk (RR) 0.27, 95% confidence interval (CI) 0.11 to 0.64), but a higher risk of other complications including infection, adhesions and disturbed skin sensibility (RR 10.60, 95%CI 4.82 to 23.28). Percutaneous repair compared with open operative repair (2 studies, 94 patients) was associated with a shorter operation duration, and lower risk of infection (RR 10.52, 95% CI 1.37 to 80.52). These figures should be interpreted with caution because of the small numbers involved. Patients splinted with a functional brace rather than a cast post-operatively (5 studies, 273 patients) tended to have a shorter in-patient stay, less time off work and a quicker return to sporting activities. There was also a lower complication rate (excluding rerupture) in the functional brace group (RR 1.88 95%CI 1.27 to 2.76). Because of the small number of patients involved no definitive conclusions could be made regarding different operative techniques (1 study, 51 patients), different non-operative treatment regimes (2 studies, 90 patients), and different forms of post-operative cast immobilisation (1 study, 40 patients). REVIEWERS' CONCLUSIONS: Open operative treatment of acute Achilles tendon ruptures significantly reduces the risk of rerupture compared to non-operative treatment, but produces a significantly higher risk of other complications, including wound infection. The latter may be reduced by performing surgery percutaneously. Post-operative splintage in a functional brace appears to reduce hospital stay, time off work and sports, and may lower the overall complication rate.

Management of concussion in collision sports. Guidelines for the sidelines.

During high-risk sports events, it is important for team physicians to be alert to the possibility of concussion in athletes who may not realize they have been injured or may want to conceal their injury. If concussion is suspected and the player is conscious, history taking should include inquiries about loss of consciousness, loss of memory of events before and after the impact, headache, visual abnormalities, motor and sensory changes, and back, neck, and extremity pain. In an unconscious player, the airway, breathing, circulation, and cervical spine should be checked. The cervical spine must be stabilized before the player is moved if injury to it is suspected. Athletes with such an injury and those who have lost consciousness require hospital evaluation. If there is no cervical spine injury, a complete neurologic evaluation should be carried out on the sidelines and the player checked for signs of skull fracture. The Colorado Medical Society guidelines for grading concussions and deciding when athletes may return to competition are an excellent aid to clinical judgment.

Consequences of not recognizing delirium superimposed on dementia in hospitalized elderly individuals.

OBJECTIVE: The purpose of this study was to describe the recognition and management of delirium in hospitalized patients with and without dementia. DESIGN: A descriptive, exploratory design was used with a convenience sample of 20 hospitalized older patients who were observed indepth using qualitative interviews and observations of 13 family members and 11 staff members. SETTING: This research was conducted on the medical-surgical units of a 550-bed, nonprofit, state-supported teaching hospital in the southeastern United States. The facility provides primary and tertiary care with five intensive care units and eight medical-surgical units. PARTICIPANTS: This study did not exclude individuals with dementia or pre-existing delirium. Subjects were not excluded on the basis of race or gender. Twenty patients in the sample underwent observation and mental and functional status testing. Thirteen family members and 11 staff members were interviewed and observed. MEASUREMENTS: In Phase 1 of the study, patients had daily mental status testing performed by the investigator. In Phase 2, family members and staff members were interviewed about the confusion event. For each patient, demographics and information regarding their health status and current diagnosis and treatment were obtained. The Mini-Mental State Examination (MMSE) and the Confusion Assessment Method were completed on each subject within 36 hours of being admitted to the hospital. The Cornell Depression Scale and Katz Activities of Daily Living scale were completed within 48 hours of admission. RESULTS: The prevalence of delirium in this study was 60%. The incidence, or new onset of delirium, was 30%. The presence of delirium was associated with new onset incontinence, lower baseline MMSE scores, depression, weight loss, and comorbidity. Of the eight individuals with delirium superimposed on dementia, 63% (n = 5) were re-admitted to the hospital within 30 days, compared to none of the individuals with delirium in the absence of dementia. Delirium superimposed on dementia also was less likely to be recognized by nurses and physicians. CONCLUSIONS: Delirium in individuals with dementia should be assessed and treated routinely because the failure to recognize delirium superimposed on dementia promptly has significant negative personal, social and financial consequences.

Diagnosing left lower lobe pneumonia: usefulness of the 'spine sign' on lateral chest radiographs.

BACKGROUND: Left lower lobe pneumonia may be obscured by the heart on the postero-anterior (PA) chest radiograph. In such cases, the lateral projection may be helpful, especially if it exhibits the "spine sign", which is an interruption in the progressive increase in lucency of the vertebral bodies from superior to inferior. We investigated whether the spine sign would help family physicians diagnose left lower lobe pneumonia on chest radiographs. METHODS: We selected the chest radiographs of all patients with left lower lobe pneumonia who were seen between 1983 and 1995 at a family practice training program (N = 78) and an equal number of chest radiographs of patients without pneumonia. Six family physicians read these radiographs under two viewing conditions: PA only vs PA and lateral. We used receiver operating characteristic (ROC) curve methodology to compare the two viewing conditions. RESULTS: There was no significant difference in performance between the two viewing conditions. The lateral view was helpful in some patients but misleading in others. Among patients with pneumonia, the lateral view was helpful when the spine sign was present, but it was misleading when the spine sign was absent. CONCLUSIONS: In this study of family physicians, the lateral chest radiograph did not improve overall diagnostic accuracy in patients with left lower lobe pneumonia. Among pneumonia patients with the spine sign, however, the lateral view was often helpful.