The vertebral end-plate has been identified as a possible source of discogenic low back pain. MRI demonstrates end-plate (Modic) changes in 20-50% of patients with low back pain. The aim of this ...study was to investigate the association between Modic changes on MRI and discogenic back pain on lumbar discography. The MRI studies and discograms of 58 patients with a clinical diagnosis of discogenic back pain were reviewed and the presence of a Modic change was correlated with pain reproduction at 152 disc levels. Twenty-three discs with adjacent Modic changes were injected, 21 of which were associated with pain reproduction. However, pain was also reproduced at 69 levels where no Modic change was seen. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for a Modic change as a marker of a painful disc were 23.3%, 96.8%, 91.3% and 46.5% respectively. Modic changes, therefore, appear to be a relatively specific but insensitive sign of a painful lumbar disc in patients with discogenic low back pain.
Lymphatic malformations (LMs) are benign abnormalities of the lymphatic system that can be significantly infiltrative and intimately involve critical structures of the head and neck, making their ...management difficult. Historically, LMs have been managed by surgical excision, but this treatment approach results in significant morbidity and a high recurrence rate secondary to subtotal resection. As an alternative to surgery a variety of drugs have been used as intralesional sclerosants and immunotherapeutics. These agents offer improved outcomes with lower morbidity as compared to surgery when targeted to macrocystic LMs. However intralesional therapy is not effective in the treatment of microcystic LMs. The development of treatments that are effective for all types of LMs will require further understanding of lymphangiogenesis and the pathogenesis of LMs. Laryngoscope, 2011
Representativeness of antihypertensive drug trials is uncertain, as many trials recruit few or no older people. Some trials specifically recruit older participants to address this. Here, we assess ...the representativeness of trials focusing on older people by comparing the rates of serious adverse events in these trials with the rates in trials of a general adult population (ie, standard trials), and comparing these findings to the rate of hospitalisations and deaths in people with hypertension starting a similar treatment in routine clinical practice.
For this observational study, we identified randomised controlled trials (phase 2/3, 3, or 4) of renin-angiotensin-aldosterone system (RAAS) drugs for hypertension registered from 1999 onwards with ClinicalTrials.gov. Serious adverse events are routinely included in trial reports and are predominantly accounted for by all-cause hospitalisations and deaths. We compared serious adverse event rates in older-people trials (minimum inclusion age ≥60 years) and standard trials (minimum inclusion age <60 years) using Poisson regression models adjusted for trial characteristics (drug type, comparison type, phase, and outcome type). We identified a community cohort of 56 036 adults with hypertension commencing similar drugs to obtain an expected rate of emergency or urgent hospitalisations or deaths, and compared this rate to observed serious adverse event rates in each trial, adjusted for age and sex. For standard trials and for older-people trials, we calculated the standardised ratio of the expected to the observed rate of serious adverse events using Poisson regression models.
We included 110 trials, of which 11 (10%) were older-people trials and 99 (90%) were standard trials. Older-people trials had a higher rate of serious adverse events than did standard trials (median events per person per year 0·18 IQR 0·12–0·29 vs 0·11 0·08–0·18; adjusted incidence rate ratio 1·76 95% CI 1·01–3·03). The hospitalisation and death rate in the community for those taking RAAS antihypertensives was much greater than the rate of serious adverse events reported in standard trials (standardised ratio SR 4·23, 95% CI 3·51–5·09) and older-people trials (4·76, 2·89–7·86), adjusting for age and sex. The magnitude of risk increase for serious adverse events in community patients taking RAAS did not differ when comparing older-people and standard trials (ratio of SRs 1·13, 95% CI 0·66–1·92).
Trials report substantially fewer serious adverse events than expected from rates of hospitalisations and deaths among similar-aged people receiving equivalent treatments in the community. Serious adverse event rates might be a useful metric to assess trial representativeness. Clinicians should be cautious when applying trial recommendations to older people, even when trials focus on older participants.
Wellcome Trust, Medical Research Council.
Abstract
Introduction
Fewer clinical trials are carried out in older people. It is unclear how representative and applicable clinical trials carried out exclusively in older people are. We compared ...clinical trials recruiting older people exclusively “older trials” to those recruiting adults of all ages “all age trials”, using anti-hypertensives acting on the renin-angiotensin aldosterone system (RAAS drugs) as an exemplar.
Method
We searched the US clinical trials register 1, to identify all trials carried out exclusively in those aged over 60. From these we selected trials of RAAS drugs. These were matched in a 2:1 ratio to trials carried out in adults of all ages. Data regarding baseline characteristics, adverse events and eligibility criteria were collected from clinical trial reports and clinicaltrials.gov. Estimated associations were calculated for age, sex and adverse events. Eligibility criteria were described and ICD- 10 coded, as appropriate.
Results
71 clinical trials were carried out exclusively in older people.13 related to RAAS drugs. Participants in “Older trials” had higher mean age (73.1 and 55.9 respectively), mean difference 16.17 (CI 15.31–17.02). Older trials had fewer male participants. Participants in older trials had lower mean body mass index (BMI). A higher rate of participants in older trials experienced serious adverse events. (2.07, CI 1.55–2.75.) Few older trials had upper age limits (23.1% V 27% all age trials). All trials had exclusion criteria in multiple ICD blocks. Concurrent medications were a more common exclusion criterion in older trials (61.5% v 40.9%).
Conclusions
Clinical trials carried out exclusively in older people are representative in terms of age, serious adverse events and eligibility. Although there are multiple exclusion criteria for clinical trial participation in both groups, this is not prohibitive. This supports carrying out more trials exclusively in older people. References 1. NIH, US national library of medicine.ClinicalTrials.gov Available at https://clinicaltrials.gov/
Improved management of mental illness and substance misuse comorbidity is a National Health Service priority, but little is known about its prevalence and current management.
To measure the ...prevalence of comorbidity among patients of community mental health teams (CMHTs) and substance misuse services, and to assess the potential for joint management.
Cross-sectional prevalence survey in four urban UK centres.
Of CMHT patients, 44% (95% CI 38.1-49.9) reported past-year problem drug use and/or harmful alcohol use; 75% (95% CI 68.2-80.2) of drug service and 85% of alcohol service patients (95% CI 74.2-93.1) had a past-year psychiatric disorder. Most comorbidity patients appear ineligible for cross-referral between services. Large proportions are not identified by services and receive no specialist intervention.
Comorbidity is highly prevalent in CMHT, drug and alcohol treatment populations, but may be difficult to manage by cross-referral psychiatric and substance misuse services as currently configured and resourced.
The determination of the centre-of-mass energies from the LEP1 data for 1993, 1994 and 1995 is presented. Accurate knowledge of these energies is crucial in the measurement of the Z resonance ...parameters. The improved understanding of the LEP energy behaviour accumulated during the 1995 energy scan is detailed, while the 1993 and 1994 measurements are revised. For 1993 these supersede the previously published values. Additional instrumentation has allowed the detection of an unexpectedly large energy rise during physics fills. This new effect is accommodated in the modelling of the beam-energy in 1995 and propagated to the 1993 and 1994 energies. New results are reported on the magnet temperature behaviour which constitutes one of the major corrections to the average LEP energy. The 1995 energy scan took place in conditions very different from the previous years. In particular the interaction-point specific corrections to the centre-of-mass energy in 1995 are more complicated than previously: these arise from the modified radiofrequency-system configuration and from opposite-sign vertical dispersion induced by the bunch-train mode of LEP operation. Finally an improved evaluation of the LEP centre-of-mass energy spread is presented. This significantly improves the precision on the Z width.
The implementation of an Internet-based Virtual Manufacturing facility for the development and optimisation of new manufacturing processes is presented. The facility integrates advanced process ...simulation software, a remote machine monitoring system and multimedia technologies to realise a virtual environment for manufacturing process optimisation. Utilising physics-based process simulations, process parameters and operational sequences are evaluated and optimised with respect to desired product features. Having optimised the operation, a prototype of the part can be created at the facility. During prototyping, process parameters are monitored in real-time. A Case Study is presented, where a 3-axis milling operation is defined, optimised and executed using the facility.
There are a large number of mouthrinse products available to the general public for use as adjuncts to oral hygiene. Many have not been evaluated and relatively few comparisons of products have been ...made. This study compared 4 mouthrinse products containing cetylpyridinium chloride (CPC), chlorhexidine, C31G, or triclosan with saline rinse included as a placebo control. Twenty dentate volunteers took part in this 4-day plaque regrowth study which had a single blind, randomized cross-over design balanced for residual effects. On day 1 of each study period, volunteers were rendered plaque free by a professional prophylaxis, suspended normal oral hygiene measures, and rinsed twice daily for 1 minute with 15 mL of the allocated rinse. On day 5, subjects were scored for disclosed plaque by plaque index and plaque area. By both measures the order of decreasing product efficacy was chlorhexidine, CPC and triclosan, C31G, and saline. All the differences in favor of the chlorhexidine product were highly significant as were those in favor of the other rinses compared to saline. It is concluded that the findings of this study reflect the actual chemical benefits of the products divorced from the indeterminate variable of toothbrushing.
The radiographic fusion rates, graft behaviour and clinical outcome of 41 patient with simultaneous combined anterior lumbar interbody fusion and posterior arthrodesis with translaminar screws were ...reviewed independently. In all patients a femoral cortical allograft (FCA) ring filled with autologous iliac crest cancellous bone was used anteriorly to replace the disc and achieve interbody fusion. The follow-up averaged 30.6 months, with a minimum follow-up of 24 months. All patients had disabling low-back pain with different degrees of radiating leg pain and either discogenic pain (n = 24) or a postdiscectomy syndrome (n = 15) respectively postfusion syndrome (n = 2). The overall fusion rate was 95.2% (59 of 62 segments). Time to radiographic fusion averaged 8.7 months (range 2-34 months), and in 66.1% radiographic fusion occurred without significant subsidence. In 18.6% fusion with subsidence resulted from resorption of the FCA and in 15.3% the FCA had protruded into the vertebral body. The posterior intervertebral disc height (PIVDH) increased postoperatively by 2 mm on average. However, loss of PIVDH was the rule, and occurred within the first 12 postoperative months, resulting in a negligible final gain in height of 0.3 mm on average. The segmental lordosis was increased by 3 degrees; however, loss of lordosis during the first 6 postoperative months led to a final gain in lordosis of 1.3 degrees on average. Graft incorporation occurred in 16 of 62 segments (25.8%) and was observed at an average of 21.9 months postoperatively. Subjectively, 82.4% of the patients were satisfied or highly satisfied with the clinical result of the fusion operation. In conclusion, the described technique has proven to be highly effective in achieving a high fusion rate with a good patient outcome.
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