Cognitive-behavioural therapy-based intervention to reduce fear of falling in older people: therapy development and randomised controlled trial - the Strategies for Increasing Independence, Confidence and Energy (STRIDE) study.

BACKGROUND: Falls cause fear, anxiety and loss of confidence, resulting in activity avoidance, social isolation and increasing frailty. The umbrella term for these problems is 'fear of falling', seen in up to 85% of older adults who fall. Evidence of effectiveness of physical and psychological interventions is limited, with no previous studies examining the role of an individually delivered cognitive-behavioural therapy (CBT) approach. OBJECTIVES: Primary objective To develop and then determine the effectiveness of a new CBT intervention (CBTi) delivered by health-care assistants (HCAs) plus usual care compared with usual care alone in reducing fear of falling. Secondary objectives To measure the impact of the intervention on falls, injuries, functional abilities, anxiety/depression, quality of life, social participation and loneliness; investigate the acceptability of the intervention for patients, family members and professionals and factors that promote or inhibit its implementation; and measure the costs and benefits of the intervention. DESIGN: Phase I CBTi development. Phase II Parallel-group patient randomised controlled trial (RCT) of the new CBTi plus usual care compared with usual care alone. SETTING: Multidisciplinary falls services. PARTICIPANTS: Consecutive community-dwelling older adults, both sexes, aged ≥ 60 years, with excessive or undue fear of falling per Falls Efficacy Scale-International (FES-I) score of > 23. INTERVENTIONS: Phase I Development of the CBTi. The CBTi was developed following patient interviews and taught to HCAs to maximise the potential for uptake and generalisability to a UK NHS setting. Phase II RCT. The CBTi was delivered by HCAs weekly for 8 weeks, with a 6-month booster session plus usual care. MAIN OUTCOME MEASURES: These were assessed at baseline, 8 weeks, 6 months and 12 months. Primary outcome measure Fear of falling measured by change in FES-I scores at 12 months. Secondary outcome measures These comprised falls, injuries, anxiety/depression [Hospital Anxiety and Depression Scale (HADS)], quality of life, social participation, loneliness and measures of physical function. There were process and health-economic evaluations alongside the trial. RESULTS: Four hundred and fifteen patients were recruited, with 210 patients randomised to CBTi group and 205 to the control group. There were significant reductions in mean FES-I [-4.02; 95% confidence interval (CI) -5.95 to -2.1], single-item numerical fear of falling scale (-1.42; 95% CI -1.87 to 1.07) and HADS (-1; 95% CI -1.6 to -0.3) scores at 12 months in the CBTi group compared with the usual care group. There were no differences in the other secondary outcome measures. Most patients found the CBTi acceptable. Factors affecting the delivery of the CBTi as part of routine practice were identified. There was no evidence that the intervention was cost-effective. CONCLUSIONS: Our new CBTi delivered by HCAs significantly improved fear of falling and depression scores in older adults who were attending falls services. There was no impact on other measures. FURTHER WORK: Further work should focus on a joint CBTi and physical training approach to fear of falling, more rational targeting of CBTi, the possibility of mixed group and individual CBTi, and the cost-effectiveness of provision of CBTi by non-specialists. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78396615. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 56. See the NIHR Journals Library website for further project information.

Regionality of disease progression predicts prognosis in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological syndrome in which motor neurons degenerate relentlessly. Although the site of onset and the rate of spread have been studied extensively, little is known about whether focal as opposed to diffuse disease affects prognosis. We therefore tested the hypothesis that regionality of disease burden is a prognostic factor in ALS. We analysed clinical data from two large multicentre, longitudinal trials. Regionality was defined as the difference in progression rates in three domains as measured by the revised ALS Functional Rating Scale, omitting the respiratory domain from analysis. We used death by trial end as the outcome variable and tested this by logistic regression against predictor variables including regionality and overall rate of disease progression. There were 561 patients. Regionality of disease was independently associated with significantly higher chance of death by study end (odds ratio most diffuse against most focal category 0.354 (0.191, 0.657), p = 0.001), with a direct relationship between degree of regionality and odds of death. We have shown using clinical trial data that focal disease is associated with a worse prognosis in ALS. Measures of regionality warrant further independent consideration in the development of future prognostic models.

Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials.

OBJECTIVES: The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages. METHODS: Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated. RESULTS: There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4. DISCUSSION: We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.

Health utility decreases with increasing clinical stage in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease typically causing death within three years. Understanding the impact of disease on patients using health utility at different stages of ALS would allow meaningful cost-benefit analysis of new potential therapies. A common health-related quality of life measurement, developed and validated for the UK, is the EQ-5D. Using clinical trial data from the LiCALS study, we calculated health utility using the EQ-5D for each King's ALS clinical stage from 214 patients. We analysed whether health utility, and other health-related measures, significantly changed between each of the clinical stages. Results showed that mean health utility decreased by 0.487 (the scale runs from 1 to - 0.594) between clinical stages 2A and 4. Emotional states, measured using the Hospital Anxiety and Depression Scale (HADS), showed worsening depression and anxiety scores as ALS progressed. Age of onset, disease onset, gender and treatment group were not predictors of EQ-5D, depression or anxiety. In conclusion, increasing severity of King's ALS Clinical Stage is associated with a progressive decrease in EQ-5D health utility. This is useful for cost-benefit analysis of new therapies and validates this ALS clinical staging system.

Study protocol for the randomised controlled trial: antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study).

BACKGROUND: Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. METHODS/DESIGN: Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. DISCUSSION: Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN45338259; EudraCT Number: 2009-015165-31.

Tonsillectomy: a cost-effective option for childhood sore throat? Further analysis of a randomized controlled trial.

OBJECTIVE: To compare the estimated cost-effectiveness of childhood (adeno)tonsillectomy vs medical therapy for recurrent sore throats from the intention-to-treat (ITT) analysis of a randomized controlled trial (RCT) with that modeled on the recorded timing of surgical interventions as observed in all participants irrespective of their original group allocation. STUDY DESIGN: A pragmatic RCT (trial) with a parallel nonrandomized patient preference group (cohort) of (adeno)tonsillectomy vs medical therapy. SETTING: Five secondary care UK otolaryngology departments. SUBJECTS AND METHODS: Eligible children, aged 4 to 15 years, were enrolled to the trial (268) or cohort (461) groups. Outcomes included sore throat diaries, quality of life, and general practice consultations. The RCT protocol ITT analysis was compared with an as-treated analysis incorporating the cohort group, modeled to reflect the timing of tonsillectomy and the differential switch rates among the original groups. RESULTS: In the RCT ITT analysis, tonsillectomy saved 3.5 sore throats, whereas the as-treated model suggested an average reduction of more than 8 sore throats in 2 years for surgery within 10 weeks of consultation, falling to only 3.5 twelve months later due to the spontaneous improvement in the medical therapy group. CONCLUSION: In eligible UK school-age children, tonsillectomy can save up to 8 sore throats at a reasonable cost, if performed promptly. Further prospective data collection, accounting for baseline and per-trial preferences and choice, is urgently needed.

Abnormal tooth size and morphology in subjects with cleft lip and/or palate in the north of England.

The aim of this study was to investigate tooth size and morphology in subjects with unilateral cleft palate (UCLP), bilateral cleft palate (BCLP), and isolated cleft palate (ICP) living in the north of England and to compare these with a control group. The measurements were undertaken retrospectively using dental study casts. To assess tooth size, the mesiodistal and buccolingual dimensions of each fully erupted permanent tooth were measured using digital Vernier callipers. The following morphological features of the teeth were assessed: upper incisor shovelling and crown form, the presence of Carabelli's tubercle on the upper molars, molar cusp number, and lower molar fissure pattern. Multilevel regression analysis was used to determine differences in tooth size, while chi-square tests and analysis of variance were used to assess differences in tooth morphology between the groups. Tooth size was reduced in all cleft groups in both jaws, with the smallest teeth being found in the ICP group. Upper lateral incisors on the cleft-affected side in UCLP and BCLP patients showed the greatest reduction in size. The upper central and lateral incisors on the cleft-affected side in the UCLP and BCLP groups were frequently hypoplastic or peg-shaped. Molar morphology in all the cleft groups was similar to that in the control group. Reduced tooth dimensions were found in both jaws in subjects with all types of clefts, suggesting a shared genetic basis. Additionally, the upper incisors were abnormal in morphology in UCLP and BCLP subjects with or without a cleft palate, suggesting shared local aetiological factors.

A pilot randomized, controlled trial of treatment for painful arc of the shoulder.

There is a lack of evidence about the efficacy of routinely used interventions in shoulder pain, such as corticosteroid injection and physiotherapy. This pilot study was set up to assess the feasibility of a larger, randomized controlled trial. Patients with the clinical presentation of a painful arc of less than 6 months' duration were recruited through their general practitioners. A total of 112 patients were randomized to 4 groups: control, physiotherapy, a course of subacromial steroid injections, or both physiotherapy and steroid injections. The primary outcome measure was the Oxford Shoulder Score (OSS). Follow-up was 18 weeks and by postal questionnaire at 1 year. No significant differences were found within groups between the OSS scores or the Physical Health total of the Medical Outcomes Study Short Form 36 (SF-36) Health Survey at the beginning and end of the trial or at 1 year. By analysis of covariance, no significant differences were found between treatment groups. Larger studies are needed. A power calculation from our data suggests recruitment of more than 800 patients would be required to achieve a 90% chance of a clinically significant difference being detected between these groups.

A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial.

OBJECTIVE: To determine the efficacy of a computerised decision aid in patients with atrial fibrillation making decisions on whether to take warfarin or aspirin therapy. DESIGN: Two-armed open exploratory randomised controlled trial. SETTING: Two research clinics deriving participants from general practices in Northeast England. PARTICIPANTS: 109 patients with atrial fibrillation aged over 60. INTERVENTIONS: Computerised decision aid applied in shared decision-making clinic compared to evidence-based paper guidelines applied as direct advice. MAIN OUTCOME MEASURES: Primary outcome measure was the decision conflict scale. Secondary outcome measures included anxiety, knowledge, decision-making preference, treatment decision, use of primary and secondary care services and health outcomes. RESULTS: Decision conflict was lower in the computerised decision aid group immediately after the clinic; mean difference -0.18 (95% CI -0.34 to -0.01). Participants in this group not already on warfarin were much less likely to start warfarin than those in the guidelines arm (4/16, 25% compared to the guidelines group 15/16, 93.8%, RR 0.27, 95% CI 0.11 to 0.63). CONCLUSIONS: Decision conflict was lower immediately following the use of a computerised decision aid in a shared decision-making consultation than immediately following direct doctor-led advice based on paper guidelines. Furthermore, participants in the computerised decision aid group were significantly much less likely to start warfarin than those in the guidelines arm. The results show that such an approach has a positive impact on decision conflict comparable to other studies of decision aids, but also reduces the uptake of a clinically effective treatment that may have important implications for health outcomes.

Amnesia for loss of consciousness in carotid sinus syndrome: implications for presentation with falls.

OBJECTIVES: The goal of this study was to compare the clinical characteristics of patients with carotid sinus syndrome who presented with falls with those who presented with syncope. BACKGROUND: Carotid sinus syndrome presents with both falls and syncope. The reasons for this differential presentation are unknown, but amnesia for loss of consciousness may be the underlying cause. METHODS: Two groups of 34 consecutive patients with carotid sinus syndrome as the sole cause of falls and syncope were recruited. Cognitive function and clinical characteristics were compared between the two groups. RESULTS: Syncopal subjects with carotid sinus syndrome were more likely to be older males (18 [53%] vs. 7 [21%] years; p = 0.006) with a longer duration of symptoms (27.9 vs. 13.3 months; p = 0.009) and more soft tissue injuries (19 [56%] vs. 9 [26%]; p = 0.03). Duration of asystole during carotid sinus massage was similar in both groups (5.1 vs. 5.4 s; p = 0.42), but witnessed amnesia for loss of consciousness was more frequent in fallers than those with syncope (21 [95%] vs. 4 [12%]; p < 0.001). Clinical characteristics and cognitive function were otherwise similar in both groups. CONCLUSIONS: Patients with carotid sinus syndrome have similar rates of witnessed loss of consciousness during laboratory testing regardless of symptoms. However, those presenting with falls are far less likely to perceive any disturbance of consciousness than those with syncope, showing for the first time the manner in which such patients manifest symptoms. Cognitive impairment does not explain the amnesia for loss of consciousness seen in fallers with carotid sinus syndrome.