Hyaluronic Acid for the Treatment of Osteoarthritis in all Joints Except the Knee

Background

The use of intra-articular hyaluronic acid (HA) is a well known treatment in patients with knee osteoarthritis (OA). In other joints, less evidence is available about the efficacy of treatment with intra-articular HA. HA is also used intra-articularly in the metatarsophalangeal-1 joint, the ankle, the hip, the sacroiliac joint, the facet joints, the carpometacarpal-1 joint, the shoulder and the temporo-mandibular joint. In this systematic review we include all prospective studies about the effects of intra-articular HA in the above-mentioned joints. Its use in the knee joint, however, will be discussed in a separate article in this journal.

Methods

A systematic review was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register, and EMBASE.

Results

After performing a solid systematic review using a rigid methodology and trying to pool the outcomes of different studies, we noticed that, compared with baseline, there is statistical evidence for a positive effect of intra-articular HA. However, there is limited evidence HA is superior to placebo and no evidence that intra-articular HA is better than corticosteroids or other conservative therapies.

Conclusion

Our recommendation for future research is that one should focus on adequately powered randomized trials comparing HA treatment with other types of intra-articular or conservative treatment. We think it is useless to further perform and publish (large) non-comparative prospective studies about the use of HA in the treatment of problems caused by OA. It is well perceived that HA exerts positive effects in the treatment of OA, but up to now there is no (strong) evidence available that HA is superior to other treatments of OA such as corticosteroids, physiotherapy or other conservative measures.     

Balancing bistable perception during self-motion

In two experiments we investigated whether bistable visual perception is influenced by passive own body displacements due to vestibular stimulation. For this we passively rotated our participants around the vertical (yaw) axis while observing different rotating bistable stimuli (bodily or non-bodily) with different ambiguous motion directions. Based on previous work on multimodal effects on bistable perception, we hypothesized that vestibular stimulation should alter bistable perception and that the effects should differ for bodily versus non-bodily stimuli. In the first experiment, it was found that the rotation bias (i.e., the difference between the percentage of time that a CW or CCW rotation was perceived) was selectively modulated by vestibular stimulation: the perceived duration of the bodily stimuli was longer for the rotation direction congruent with the subject’s own body rotation, whereas the opposite was true for the non-bodily stimulus (Necker cube). The results found in the second experiment extend the findings from the first experiment and show that these vestibular effects on bistable perception only occur when the axis of rotation of the bodily stimulus matches the axis of passive own body rotation. These findings indicate that the effect of vestibular stimulation on the rotation bias depends on the stimulus that is presented and the rotation axis of the stimulus. Although most studies on vestibular processing have traditionally focused on multisensory signal integration for posture, balance, and heading direction, the present data show that vestibular self-motion influences the perception of bistable bodily stimuli revealing the importance of vestibular mechanisms for visual consciousness.     

The incremental value of brachial flow-mediated dilation measurements in risk stratification for incident cardiovascular events: a systematic review

Abstract Adequate risk assessment for cardiovascular disease (CVD) is essential as a guide to initiate drug treatment. Current methods based on traditional risk factors could be improved considerably. Although brachial flow-mediated dilation (FMD) predicts subsequent cardiovascular events, its predictive value on top of traditional risk factors is unknown. We performed a systematic review to evaluate the incremental predictive value of FMD on top of traditional risk factors in asymptomatic individuals. Using PubMed and reference tracking, three studies were identified that reported on the incremental value of FMD using change in the area under the curve (AUC). Two large cohort studies found no improvement in AUC when FMD was added to traditional risk prediction models, whereas one small case-control study found an improvement. One study used the net reclassification improvement (NRI) to assess whether FMD measurement leads to correct risk stratification in risk categories. Although this study did not find an improvement in AUC, the NRI was statistically significant. Based on the reclassification results of this study, FMD measurement might be helpful in risk prediction. Evidence supporting the use of FMD measurement in clinical practice for risk stratification for CVD on top of traditional risk factors is limited, and future studies are needed.     

T-cell ageing in end-stage renal disease patients: Assessment and clinical relevance

End-stage renal disease (ESRD) patients have a defective T-cell-mediated immune system which is related to excessive premature ageing of the T-cell compartment. This is likely to be caused by the uremia-associated pro-inflammatory milieu, created by loss of renal function. Therefore, ESRD patients are highly susceptible for infections, have an increased risk for virus-associated cancers, respond poorly to vaccination and have an increased risk for atherosclerotic diseases. Three ageing parameters can be used to assess an immunological T-cell age. First, thymic output can be determined by assessing the T-cell receptor excision circles-content together with CD31 expression within the naïve T cells. Second, the telomere length of T cells and third the T-cell differentiation status are also indicators of T-cell ageing. Analyses based on these parameters in ESRD patients revealed that the immunological T-cell age is increased by on average 20 years compared to the chronological age. After kidney transplantation (KTx) the aged T-cell phenotype persists although the pro-inflammatory milieu is diminished. This might be explained by epigenetic modifications at hematopoietic stem cells level. Assessment of an immunological T-cell age could be an important tool to identify KTx recipients who are at risk for allograft rejection or to prevent over-immunosuppression.     

Accelerating vaccine trial conduct in a pandemic with a hot spot‐based inclusion strategy using trial and epidemic simulation

Clinical development of vaccines in a pandemic situation should be rigorous but expedited to tackle the pandemic threat as fast as possible. We explored the effects of a novel vaccine trial strategy that actively identifies and enrolls subjects in local areas with high infection rates. In addition, we assessed the practical requirements needed for such a strategy. Clinical trial simulations were used to assess the effects of utilizing these so‐called “hot spot strategy” compared to a traditional vaccine field trial. We used preset parameters of a pandemic outbreak and incorporated realistic aspects of conducting a trial in a pandemic setting. Our simulations demonstrated that incorporating a hot spot strategy shortened the duration of the vaccine trial considerably, even if only one hot spot was identified during the clinical trial. The active hot spot strategy described in this paper has clear advantages compared to a “wait‐and‐see” approach that is used in traditional vaccine efficacy trials. Completion of a clinical trial can be expedited by adapting to resurgences and outbreaks that will occur in a population during a pandemic. However, this approach requires a speed of response that is unusual for a traditional phase III clinical trial. Therefore, several recommendations are made to help accomplish rapid clinical trial setup in areas identified as local outbreaks. The described model and hot spot vaccination strategy can be adjusted to disease‐specific transmission characteristics and could therefore be applied to any future pandemic threat.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Clinical development of vaccines in a pandemic situation requires a different development paradigm. It should be rigorous but expedited to tackle the pandemic threat as fast as possible. Field trials are considered pivotal, but are also the most time‐consuming stage of clinical vaccine development.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Would a novel vaccine trial strategy that actively identifies and enrolls subjects in local areas with high infection rates shorten the duration of a vaccine field trial compared to the traditional wait‐and‐see approach?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

By using clinical trial simulations it was demonstrated that trial duration can be shortened considerably if local outbreaks are identified and subjects from these outbreaks are enrolled in the clinical trial. Recommendations are made to facilitate this novel approach.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study provides new insight in possible strategies to expedite clinical vaccine development and is in support of a more agile approach to conduct vaccine trials during a pandemic.     

10th International Symposium on Head And Neck Skin Cancer

Since 1993, ten multidisciplinary symposia were organized at The Netherlands Cancer Institute on the diagnosis and treatment of malignancies of the head and neck. The symposia are meant to provide up-to-date teaching for physicians by world-renowned speakers. The previous symposia dealt with sarcomas, reconstruction, cancer in young patients, salivary glands, melanoma, unknown primaries, as well as several other topics. This 10th symposium focused on skin cancer of the head and neck. There are many types of skin cancer and the differential diagnosis can often be difficult. In this symposium, diagnosis, molecular biology, epidemiology, staging and the treatment of various skin cancers were discussed by leaders in the field. There were over 200 participants from many different countries in Europe and overseas, representing specialties in the fields of dermatology, maxillofacial surgery, otolaryngology, head and neck surgery, general surgery, plastic and reconstructive surgery, and radiotherapy.