Viscosupplementation for the treatment of osteoarthritis of the knee (Review)

Background Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. Objectives To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). Search strategy MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. Selection criteria RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). Data collection and analysis Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer. Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). Main results Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Authors' conclusions Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients

Aim To explore relationships between sirolimus dosing, concentration and clinical outcomes. Methods Data were collected from 25 kidney transplant recipients (14 M/11 F), median 278 days after transplantation. Outcomes of interest were white blood cell (WBC) count, platelet (PLT) count, and haematocrit (HCT). A naive pooled data analysis was performed with outcomes dichotomized (Mann-Whitney U-tests). Results Several patients experienced at least one episode when WBC (n = 9), PLT (n = 12), or HCT (n = 21) fell below the lower limits of the normal range. WBC and HCT were significantly lower (P < 0.05) when sirolimus dose was greater than 10 mg day(-1), and sirolimus concentration greater than 12 mu g l(-1). No relationship was shown for PLT and dichotomized sirolimus dose or concentration. Conclusions Given this relationship between sirolimus concentration and effect, linked population pharmacokinetic-pharmacodynamic modelling using data from more renal transplant recipients should now be used to quantify the time course of these relationships to optimize dosing and minimize risk of these adverse outcomes.

Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies

Nitric Oxide (NO) plays a controversial role in the pathophysiology of sepsis and septic shock. Its vasodilatory effects are well known, but it also has pro- and antiinflammatory properties, assumes crucial importance in antimicrobial host defense, may act as an oxidant as well as an antioxidant, and is said to be a vital poison for the immune and inflammatory network. Large amounts of NO and peroxynitrite are responsible for hypotension, vasoplegia, cellular suffocation, apoptosis, lactic acidosis, and ultimately multiorgan failure. Therefore, NO synthase (NOS) inhibitors were developed to reverse the deleterious effects of NO. Studies using these compounds have not met with uniform success however, and a trial using the nonselective NOS inhibitor N-G-methyl-L-arginine hydrochloride was terminated prematurely because of increased mortality in the treatment arm despite improved shock resolution. Thus, the issue of NOS inhibition in sepsis remains a matter of debate. Several publications have emphasized the differences concerning clinical applicability of data obtained from unresuscitated, hypodynamic rodent models using a pretreatment approach versus resuscitated, hyperdynamic models in high-order species using posttreatment approaches. Therefore, the present review focuses on clinically relevant large-animal studies of endotoxin or living bacteria-induced, hyperdynamic models of sepsis that integrate standard day-today care resuscitative measures.

Looking beyond the negatives: A time period analysis of positive cognitions, negative cognitions, and working alliance in cognitive-behavior therapy for panic disorder

Time period analysis was used in an international sample of clients ( N = 106) to demonstrate that cognitive - behavioral therapy (CBT) for panic disorder is associated with specific changes in both negative and positive cognitions during the treatment period. In the first 6 weeks of the treatment phase, working alliance failed to predict changes in panic severity, whereas changes in panic self-efficacy and catastrophic misinterpretation of bodily sensations predicted rapid symptom relief. In the last 6 weeks of treatment, higher doses of CBT were associated with further changes in positive and negative cognitions. The findings can be interpreted as suggesting that the role of the working alliance in CBT for panic disorder is to facilitate cognitive change.

Early combination disease modifying antirheumatic drug treatment for rheumatoid arthritis

Most people presenting with rheumatoid arthritis today can expect to achieve disease suppression, can avoid or substantially delay joint damage and deformities, and can maintain a good quality of life. Optimal management requires early diagnosis and treatment, usually with combinations of conventional disease modifying antirheumatic drugs (DMARDs). If these do not effect remission, biological DMARDs may be beneficial. Lack of recognition of the early signs of rheumatoid arthritis, ignorance of the benefits of early application of modern treatment regimens, and avoidable delays in securing specialist appointments may hinder achievement of best outcomes for many patients. Triage for recognising possible early rheumatoid arthritis must begin in primary care settings with the following pattern of presentation as a guide: involvement of three or more joints; early-morning joint stiffness of greater than 30 minutes; or bilateral squeeze tenderness at metacarpophalangeal or metatarsophalangeal joints.

Normal ranges for automated analysis of global LV function using 2D Strain

Background: Automated measurement of LV function could extend the clinical utility of echo by less expert readers. We sought to define normal ranges of global 2D strain (2DS) and strain-rate (SR) in an international, multicenter study of healthy subjects, and to assess the determinants of variation. Methods: SR and 2DS were measured in 18 myocardial segts in both apical and short axis views of 227 normal subjects (38% men, 48±14y) with no cardiac history, risk factors or drug therapy. The association of age and resting hemodynamics with global strain indices was sought using multiple regression. Differences in variance were expressed as F values. Results: Baseline SBP was 127±18 mmHg, pulse was 76±13/min and ejection fraction 50±20%. Although global longitudinal strain was influenced by endsystolic volume (F=4.2, p

Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial

Background: Currently 1 in 11 women over the age of 60 in Australia are diagnosed with breast cancer. Following treatment, most breast cancer patients are left with shoulder and arm impairments which can impact significantly on quality of life and interfere substantially with activities of daily living. The primary aim of the proposed study is to determine whether upper limb impairments can be prevented by undertaking an exercise program of prolonged stretching and resistance training, commencing soon after surgery. Methods/design: We will recruit 180 women who have had surgery for early stage breast cancer to a multicenter single-blind randomized controlled trial. At 4 weeks post surgery, women will be randomly assigned to either an exercise group or a usual care ( control) group. Women allocated to the exercise group will perform exercises daily, and will be supervised once a week for 8 weeks. At the end of the 8 weeks, women will be given a home-based training program to continue indefinitely. Women in the usual care group will receive the same care as is now typically provided, i.e. a visit by the physiotherapist and occupational therapist while an inpatient, and receipt of pamphlets. All subjects will be assessed at baseline, 8 weeks, and 6 months later. The primary measure is arm symptoms, derived from a breast cancer specific questionnaire (BR23). In addition, range of motion, strength, swelling, pain and quality of life will be assessed. Discussion: This study will determine whether exercise commencing soon after surgery can prevent secondary problems associated with treatment of breast cancer, and will thus provide the basis for successful rehabilitation and reduction in ongoing problems and health care use. Additionally, it will identify whether strengthening exercises reduce the incidence of arm swelling. Trial Registration: The protocol for this study is registered with the Australian Clinical Trials Registry (ACTRN012606000050550).

Stage is not a reliable indicator of tumor volume in non-small cell lung cancer: a preliminary analysis of the trans-tasman radiation oncology group 99-05 database

Background: Tumor volume has been shown to be a prognostic factor for the response of some tumors to radiotherapy. TNM stage has prognostic value for patients treated surgically for non-small cell lung cancer (NSCLC), but its value is less clear for patients treated by nonsurgical means. This may be because tumor size is not a consistent determinant of T stage or stage group. As part of the preliminary analyses for the Trans-Tasman Radiation Oncology Group 99-05 study, the authors performed this analysis to determine to what extent stage reflects tumor volume. Methods: In this prospective multicenter observational study, patients had to have histologically proven NSCLC, no evidence of disease beyond the primary site or thoracic lymph nodes, and been planned for radical radiotherapy with or without chemotherapy. Tumor volume measurements were based on computed tomography-based treatment planning images. Results: Four hundred four patients were available for analysis. There was a strong correlation between (log) maximum tumor diameter and (log) tumor volume (r = 0.93, p < 0.001). Although there was a highly significant trend of increasing volume with increasing T stage and stage group, when tumors were categorized into four groups according to increasing volume, there was only 55% concordance with T stage and 67% concordance with stage group. Conclusions: There is limited correlation between tumor size and disease stage in patients with NSCLC. This justifies documentation and investigation of size as a potential prognostic factor independent of stage. Maximum tumor diameter may be an adequate substitute for volume as a measurement of size.

Head and neck cancer: past, present and future

Head and neck cancer consists of a diverse group of cancers that ranges from cutaneous, lip, salivary glands, sinuses, oral cavity, pharynx and larynx. Each group dictates different management. In this review, the primary focus is on head and neck squamous cell carcinoma (HNSCC) arising from the mucosal lining of the oral cavity and pharynx, excluding nasopharyngeal cancer. Presently, HNSCC is the sixth most prevalent neoplasm in the world, with approximately 900,000 cases diagnosed worldwide. Prognosis has improved little in the past 30 years. In those who have survived, pain, disfigurement and physical disability from treatment have had an enormous psychosocial impact on their lives. Management of these patients remains a challenge, especially in developing countries where this disease is most common. Of all human cancers, HNSCC is the most distressing since the head and neck is the site of the most complex functional anatomy in the human body. Its areas of responsibility include breathing, the CNS, vision, hearing, balance, olfaction, taste, swallowing, voice, endocrine and cosmesis. Cancers that occur in this area impact on these important human functions. Consequently, in treating cancers of the head and neck, the effects of the treatment on the functional outcome of the patient need the most serious consideration. In assessing the success of HNSCC treatment, consideration of both the survival and functional deficits that the patient may suffer as a consequence of their treatment are of paramount importance. For this reason, the modern-day management of head and neck patients should be carried out in a multidisciplinary head and neck clinic.

A prospective assessment of SRS-24 scores after endoscopic anterior instrumentation for scoliosis

Study Design. Prospective clinical case series. Objective. To evaluate the clinical outcome of anterior endoscopic instrumention for scoliosis using the SRS-24 questionnaire and to examine how these scores change over a 2-year follow-up period. Summary of Background Data. Anterior endoscopic instrumentation correction has several advantages compared with open procedures. However, the clinical results of this technique using a validated outcome measure have rarely been reported in the literature. Methods. A total of 83 consecutive patients underwent endoscopic anterior instrumentation performed at a single unit. Patients completed the SRS-24 questionnaire before surgery and at 3, 6, 12, and 24 months after surgery. The SRS-24 scores were compared between each of the follow-up intervals. Results. The pain, general self-image, and function from back condition domains improved after surgery (P < 0.05). Activity level significantly improved between 3 and 6 months, and both function domains improved between 6 and 12 months (P < 0.05). None of the domains increased significantly after 1 year. Conclusions. Endoscopic anterior instrumentation for scoliosis significantly improved pain, self-image, and function. The greatest improvement in function occurred between 6 and 12 months after surgery. The SRS-24 scores at 1 year from surgery may provide a good indicator of patient outcome in the long-term.

Neonatal neurodevelopment outcomes following tocolysis with glycerol trinitrate patches

Objective: The object of this study was to determine the effects of maternal tocolysis with glycerol trinitrate (GTN) patches on the neurodevelopment of infants. Study design: This was a randomized, multicenter, controlled trial comparing the efficacy of GTN patches with standard beta 2 agonist as tocolytic therapy. The previously reported outcomes of this study indicated no difference in neonatal mortality or morbidity to hospital discharge. One hundred fifty-six surviving infants from 2 Australian centers were psychometrically assessed using the Griffiths Mental development Scales (revised) at 18 months of age. Results: There was no difference in psychometric performance between those infants enrolled in either the GTN (81 infants) or beta 2 agonist (75 infants) arm of the study. Conclusion: This randomized trial supports no significant difference between GTN patches in comparison with standard beta 2 agonist for tocolytic therapy. The results underscore the association between premature labor and adverse infant outcomes. (c) 2006 Mosby, Inc. All rights reserved.

Idiopathic sclerosing orbital inflammation

Objective: To perform a multicenter review of the clinical features and treatment of 31 patients with idiopathic sclerosing orbital inflammation. Methods: We included all patients with histologically confirmed idiopathic sclerosing orbital inflammation from 5 regional orbital centers. We reviewed the case notes to determine the clinical presentation, diagnostic features, and response to treatment. The main outcome measures were duration and nature of symptoms, anatomical location of disease, histopathological findings, treatment modalities, treatment efficacy and adverse effects, and final clinical status. Results: We included 13 male and 18 female patients ranging in age from 7 to 83 years. The average duration of symptoms at presentation was 13.4 months. There was a predilection for the lateral and superior quadrants. Thirteen patients had apical disease, and 4 had extraorbital involvement. Histopathological findings invariably showed sclerosis associated with a sparse mixed cellular infiltrate. Twenty- seven patients were treated with oral prednisolone, response to which was good in 9 patients, partial in 11, and poor in 7. Six patients were treated with a second- line immunosuppressive agent, and 6 received radiotherapy. The response to radiotherapy was generally poor. Conclusions: Idiopathic sclerosing orbital inflammation is a rare condition that can be difficult to diagnose and manage. Early intervention with immunosuppression in the form of corticosteroids combinedwith secondline agents can result in control and even regression of the disease.