St. Luke's Hospital

BACKGROUND: Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, we hypothesized that activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. METHODS: We sequenced the KCNJ11 gene in 29 patients with permanent neonatal diabetes. The insulin secretory response to intravenous glucagon, glucose, and the sulfonylurea tolbutamide was assessed in patients who had mutations in the gene. RESULTS: Six novel, heterozygous missense mutations were identified in 10 of the 29 patients. In two patients the diabetes was familial, and in eight it arose from a spontaneous mutation. Their neonatal diabetes was characterized by ketoacidosis or marked hyperglycemia and was treated with insulin. Patients did not secrete insulin in response to glucose or glucagon but did secrete insulin in response to tolbutamide. Four of the patients also had severe developmental delay and muscle weakness; three of them also had epilepsy and mild dysmorphic features. When the most common mutation in Kir6.2 was coexpressed with sulfonylurea receptor 1 in Xenopus laevis oocytes, the ability of ATP to block mutant K(ATP) channels was greatly reduced. CONCLUSIONS: Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. Identification of the genetic cause of permanent neonatal diabetes may facilitate the treatment of this disease with sulfonylureas.

OBJECTIVE: To undertake a systematic inquiry into the incidence and consequences of falls in a cohort of elderly patients with stroke after discharge from hospital. DESIGN: Administration of a questionnaire to patients and main carers at discharge from hospital and eight weeks and six months later. SETTING: Bradford Metropolitan District. SUBJECTS: 108 patients recruited to the Bradford community stroke trial. Patients were recruited to the trial if they were 60 years or over and resident at home with some residual disability. MAIN OUTCOME MEASURES: Number of falls, motor club assessment, Barthel index, Frenchay activities index, and Nottingham health profile. Stress in carers was indicated by the general health questionnaire. RESULTS: Of 108 patients, 79 (73%) fell in the six months after discharge from hospital with a total of 270 falls reported. Patients who fell in hospital were significantly more likely to fall at least twice at home after discharge (chi 2 = 8.16; P = 0.004). "Fallers" (two or more falls) were less socially active at six months and more had depressed mood. Carers of these patients were significantly more stressed at six months (53% v 18%; chi 2 = 8.5; P = 0.003). CONCLUSION: Stroke is associated with a risk of falling at home and affects the lives of patients with stroke and their carers. Falling and fear of falling is an important issue which needs to be dealt with by the multidisciplinary team.

Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

BACKGROUND: delirium is a common clinical problem and is associated with adverse health outcomes. Many medications have been associated with the development of delirium, but the strength of the associations is uncertain and it is unclear which medications should be avoided in people at risk of delirium. METHODS: we conducted a systematic review to identify prospective studies that investigated the association between medications and risk of delirium. A sensitivity analysis was performed to construct an evidence hierarchy for the risk of delirium with individual agents. RESULTS: a total of 18,767 studies were identified by the search strategy. Fourteen studies met the inclusion criteria. Delirium risk appears to be increased with opioids (odds ratio [OR] 2.5, 95% CI 1.2-5.2), benzodiazepines (3.0, 1.3-6.8), dihydropyridines (2.4, 1.0-5.8) and possibly antihistamines (1.8, 0.7-4.5). There appears to be no increased risk with neuroleptics (0.9, 0.6-1.3) or digoxin (0.5, 0.3-0.9). There is uncertainty regarding H(2) antagonists, tricyclic antidepressants, antiparkinson medications, steroids, non-steroidal anti-inflammatory drugs and antimuscarinics. CONCLUSION: for people at risk of delirium, avoid new prescriptions of benzodiazepines or consider reducing or stopping these medications where possible. Opioids should be prescribed with caution in people at risk of delirium, but this should be tempered by the observation that untreated severe pain can itself trigger delirium. Caution is also required when prescribing dihydropyridines and antihistamine H1 antagonists for people at risk of delirium and considered individual patient assessment is advocated.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

OBJECTIVE: the Barthel Index (BI) has been recommended for the functional assessment of older people but the reliability of the measure for this patient group is uncertain. To investigate this issue we undertook a systematic review to identify relevant studies from which an overview is presented. METHOD: studies investigating the reliability of the BI were obtained by searching Medline, Cinahl and Embase to January 2003. Screening for potentially relevant papers and data extraction of the studies meeting the inclusion criteria were carried out independently by two researchers. RESULTS: the scope of the 12 studies identified included all the common clinical settings relevant to older people. No study investigated test-retest reliability. Inter-rater reliability was reported as 'fair' to 'moderate' agreement for individual BI items, and a high percentage agreement for the total BI score. However, these findings were difficult to interpret as few studies reported the prevalence of the disability categories for the study populations. There may be considerable inter-observer disagreement (95% CI of +/-4 points). There was evidence that the BI might be less reliable in patients with cognitive impairment and when scores obtained by patient interview are compared with patient testing. The role of assessor training and/or guidelines on the reliability of the BI has not been investigated. CONCLUSIONS: although the BI is highly recommended, there remain important uncertainties concerning its reliability when used with older people. Further studies are justified to investigate this issue.

BACKGROUND: Retention is the phase of orthodontic treatment that attempts to keep teeth in the corrected positions after treatment with orthodontic braces. Without a phase of retention, there is a tendency for teeth to return to their initial position (relapse). To prevent relapse, almost every person who has orthodontic treatment will require some type of retention. OBJECTIVES: To evaluate the effects of different retention strategies used to stabilise tooth position after orthodontic braces. SEARCH METHODS: We searched the following databases: the Cochrane Oral Health Group's Trials Register (to 26 January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 12), MEDLINE via Ovid (1946 to 26 January 2016) and EMBASE via Ovid (1980 to 26 January 2016). We searched for ongoing trials in the US National Institutes of Health Trials Register (ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform. We applied no language or date restrictions in the searches of the electronic databases. We contacted authors of randomised controlled trials (RCTs) to help identify any unpublished trials. SELECTION CRITERIA: RCTs involving children and adults who had had retainers fitted or adjunctive procedures undertaken to prevent relapse following orthodontic treatment with braces. DATA COLLECTION AND ANALYSIS: Two review authors independently screened eligible studies, assessed the risk of bias in the trials and extracted data. The outcomes of interest were: how well the teeth were stabilised, failure of retainers, adverse effects on oral health and participant satisfaction. We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous data and risk ratios (RR) with 95% CI for dichotomous outcomes. We conducted meta-analyses when studies with similar methodology reported the same outcome. We prioritised reporting of Little's Irregularity Index to measure relapse. MAIN RESULTS: We included 15 studies (1722 participants) in the review. There are also four ongoing studies and four studies await classification. The 15 included studies evaluated four comparisons: removable retainers versus fixed retainers (three studies); different types of fixed retainers (four studies); different types of removable retainers (eight studies); and one study compared a combination of upper thermoplastic and lower bonded versus upper thermoplastic with lower adjunctive procedures versus positioner. Four studies had a low risk of bias, four studies had an unclear risk of bias and seven studies had a high risk of bias. Removable versus fixed retainers Thermoplastic removable retainers provided slightly poorer stability in the lower arch than multistrand fixed retainers: MD (Little's Irregularity Index, 0 mm is stable) 0.6 mm (95% CI 0.17 to 1.03). This was based on one trial with 84 participants that was at high risk of bias; it was low quality evidence. Results on retainer failure were inconsistent. There was evidence of less gingival bleeding with removable retainers: RR 0.53 (95% CI 0.31 to 0.88; one trial, 84 participants, high risk of bias, low quality evidence), but participants found fixed retainers more acceptable to wear, with a mean difference on a visual analogue scale (VAS; 0 to 100; 100 being very satisfied) of -12.84 (95% CI -7.09 to -18.60). Fixed versus fixed retainersThe studies did not report stability, adverse effects or participant satisfaction. It was possible to pool the data on retention failure from three trials that compared polyethylene ribbon bonded retainer versus multistrand retainer in the lower arch with an RR of 1.10 (95% CI 0.77 to 1.57; moderate heterogeneity; three trials, 228 participants, low quality evidence). There was no evidence of a difference in failure rates. It was also possible to pool the data from two trials that compared the same types of upper fixed retainers, with a similar finding: RR 1.25 (95% CI 0.87 to 1.78; low heterogeneity; two trials, 174 participants, low quality evidence). Removable versus removable retainersOne study at low risk of bias comparing upper and lower part-time thermoplastic versus full-time thermoplastic retainer showed no evidence of a difference in relapse (graded moderate quality evidence). Another study, comparing part-time and full-time wear of lower Hawley retainers, found no evidence of any difference in relapse (low quality evidence). Two studies at high risk of bias suggested that stability was better in the lower arch for thermoplastic retainers versus Hawley, and for thermoplastic full-time versus Begg (full-time) (both low quality evidence).In one study, participants wearing Hawley retainers reported more embarrassment more often than participants wearing thermoplastic retainers: RR 2.42 (95% CI 1.30 to 4.49; one trial, 348 participants, high risk of bias, low quality evidence). They also found Hawley retainers harder to wear. There was conflicting evidence about survival rates of Hawley and thermoplastic retainers. Other retainer comparisonsAnother study with a low risk of bias looked at three different approaches to retention for people with crowding, but normal jaw relationships. The study found that there was no evidence of a difference in relapse between the combination of an upper thermoplastic and lower canine to canine bonded retainer and the combination of an upper thermoplastic retainer and lower interproximal stripping, without a lower retainer. Both these approaches are better than using a positioner as a retainer. AUTHORS' CONCLUSIONS: We did not find any evidence that wearing thermoplastic retainers full-time provides greater stability than wearing them part-time, but this was assessed in only a small number of participants.Overall, there is insufficient high quality evidence to make recommendations on retention procedures for stabilising tooth position after treatment with orthodontic braces. Further high quality RCTs are needed.

OBJECTIVE: To evaluate an existing tool (the Swedish modification of the Psoriasis Assessment Questionnaire) and to develop a new instrument to screen for psoriatic arthritis in people with psoriasis. DESIGN: The starting point was a community-based survey of people with psoriasis using questionnaires developed from the literature. Selected respondents were examined and additional known cases of psoriatic arthritis were included in the analysis. The new instrument was developed using univariate statistics and a logistic regression model, comparing people with and without psoriatic arthritis. The instruments were compared using receiver operating curve (ROC) curve analysis. RESULTS: 168 questionnaires were returned (response rate 27%) and 93 people attended for examination (55% of questionnaire respondents). Of these 93, twelve were newly diagnosed with psoriatic arthritis during this study. These 12 were supplemented by 21 people with known psoriatic arthritis. Just 5 questions were found to be significant predictors of psoriatic arthritis in this population. Figures for sensitivity and specificity were 0.92 and 0.78 respectively, an improvement on the Alenius tool (sensitivity and specificity, 0.63 and 0.72 respectively). CONCLUSIONS: A new screening tool for identifying people with psoriatic arthritis has been developed. Five simple questions demonstrated good sensitivity and specificity in this population but further validation is required.

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations. OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort. METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases. RESULTS: and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003). CONCLUSIONS: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP.

BACKGROUND: A range of neuropathological and psychosocial factors have been implicated in the aetiology and maintenance of post-concussional syndrome (PCS), with a growing consensus in the literature that this is a complex, multifactorial condition. The role of patients' perceptions in PCS has not been examined to date. OBJECTIVE: This longitudinal study examines the role of illness perceptions in predicting outcome following mild head injury, controlling for severity of injury, post-traumatic stress symptoms, anxiety and depression, using a logistic regression analysis. METHOD: 73 patients were admitted to an accident and emergency department with mild head injury (Glasgow Coma Scale score 13-15; loss of consciousness <20 min; post-traumatic amnesia <24 h). Data on PCS symptomatology, illness perceptions, post-traumatic stress symptoms, anxiety and depression were collected after the injury and at the 3 month follow-up. Logistic regression analysis was used to evaluate predictors of outcome. RESULTS: Following a mild head injury, symptomatic patients who believe that their symptoms have serious negative consequences on their lives and will continue to do so, are at heightened risk of experiencing significant enduring post-concussional symptoms (p<0.001). Adding measures of severity of injury, post-traumatic stress symptoms, anxiety and depression to the regression model did not improve prediction of outcome. CONCLUSION: Whatever other physical or psychological factors may be involved, patients' perceptions of their illness early after head injury play a part in the persistence of PCS.

OBJECTIVE: There is controversy about the severity of peripheral psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA). Early reports found PsA to be a milder disorder, excepting the mutilans form. Recent reports suggest that PsA can be as severe as RA. We compared severity, disability, and quality of life in patients with PsA and RA matched primarily for disease duration. METHODS: Data relating to the extent and severity of disease were recorded in a hospital clinic setting. Recent radiographs of hands and feet were read blinded to diagnosis, and information on function and quality of life was collected with the Health Assessment Questionnaire (HAQ) and EuroQol-5D, respectively. RESULTS: Forty-seven patients were matched for disease duration (median PsA 5 yrs, RA 7 yrs). The male/female ratio was 24/23 for PsA, 16/31 for RA, and median ages were 45 and 51 years, respectively. Patients with RA had significantly more joint involvement of metacarpophalangeal joints and wrists, whereas distal interphalangeal joints, spine, sternoclavicular joints, and sacroiliac joints were significantly more involved in PsA. No difference was found regarding Ritchie Articular Index, inflammatory markers, HAQ score, or EuroQol-5D. Patients with RA had significantly more damage on radiographs of hands and feet: median (range) Larsen score hands PsA 8 (0-91), RA 38 (0-125); feet PsA 4 (0-34), RA 11(0-56). Patients with RA were taking significantly more disease modifying drugs. CONCLUSION: Peripheral joint damage is significantly greater in RA than in PsA after equivalent disease duration, but function and quality of life scores are the same for both groups. The additional burden of skin disease in PsA may account for this.

OBJECTIVE: To determine the prevalence of psoriatic arthritis (PsA) using the ClASsification criteria for Psoriatic ARthritis (CASPAR) for classification. METHODS: People with psoriasis were identified from the computerized morbidity indices of 2 large UK general practices, total population 22,500. Questionnaires were mailed to all 633 patients thus identified. Of the respondents, a 50% sample was assessed clinically and a proportion had blood samples and radiographs taken. Patients labeled as having psoriasis were also cross-referenced with a local secondary care morbidity index for PsA and rheumatoid arthritis. Figures for the prevalence of PsA were estimated from these data. RESULTS: One hundred sixty-eight questionnaires were returned (response rate 27%) and 93 people (55% of questionnaire respondents) were examined. Of these 93 people, 12 (4 of whom were cross-referenced to the hospital database) were thought to have PsA clinically, all fulfilling the CASPAR criteria for PsA. Six of the 93 examined patients did not have psoriasis or a family history of psoriasis and had no historical features or clinical signs of psoriasis on interview and examination. Extrapolating from the data of those people actually examined, the estimated (corrected) prevalence was 13.8% (95% confidence interval 7.1-24.1%). CONCLUSION: The estimated prevalence of PsA in this population, using the CASPAR criteria, was 13.8%. Misclassification of psoriasis and arthritis, and response bias, indicate that this is probably an overestimate.

Abstract Objective : To evaluate whether specialist nurse visits enhance the social integration and perceived health of patients with stroke or alleviate stress in carers in longer term stroke care. Design : Stratified randomised controlled trial; both groups assessed at time of recruitment and at 3, 6, and 12 months. Setting : Patients with disability related to new stroke who lived in their own homes in the Bradford Metropolitan District. Subjects : 240 patients aged 60 years or over, randomly allocated to control group (n = 120) or intervention group (n = 120). Intervention : Visits by specialist outreach nurses over 12 months to provide information, advice, and support; minimum of six visits during the first six months. The control group received no visits. Main outcome measures : The Barthel index (functional ability), the Frenchay activities index (social activity), the Nottingham health profile (perceived health status). Stress among carers was indicated by the general health questionnaire-28 (28 items). The nurses recorded their interventions in trial diaries. Results : There were no significant differences in perceived health, social activities, or stress among carers between the treatment and control groups at any of the assessments points. A subgroup of mildly disabled patients with stroke (Barthel index 15-19) had an improved social outcome at six months (Frenchay activities index, median difference 3 (95% confidence interval 0 to 6; P = 0.03)) and for the full 12 months of follow up (analysis of covariance P = 0.01) compared with the control group. Conclusions : The specialist nurse intervention resulted in a small improvement in social activities only for the mildly disabled patients. No proved strategy yet exists that can be recommended to address the psychosocial difficulties of patients with stroke and their families. Key messages This randomised controlled trial using specialist nurses in an intervention strategy found that no significant differences were seen at one year follow up between the two groups of patients in wellbeing or social activities and no reduction in stress among carers A significant but small increase in social activities was reported by a subgroup of mildly disabled patients with stroke No proved strategy yet exists to address the psychosocial difficulties of patients with stroke and their families

BACKGROUND: Mutations in the fukutin-related protein gene FKRP cause limb-girdle muscular dystrophy (LGMD2I) as well as a form of congenital muscular dystrophy (MDC1C). OBJECTIVE: To define the phenotype in LGMD2I. METHODS: The authors assessed 16 patients from 14 families with FKRP gene mutations and LGMD and collected the results of mutation analysis, protein studies, and respiratory and cardiac investigations. RESULTS: Thirteen patients, most with adult presentation, were homozygous for the common C826A mutation in FKRP. The three other cases were compound heterozygotes for C826A and two of them presented in childhood, with more progressive disease. The pattern of muscle involvement, frequently including calf hypertrophy, was similar to dystrophinopathy. Complications in patients with LGMD2I were common and sometimes out of proportion to the skeletal muscle involvement. Six patients had cardiac involvement, and 10 had respiratory impairment: five required nocturnal respiratory support. All patients had serum creatine kinase at least 5 to 70 times normal. The most consistent protein abnormality found on muscle biopsy was a reduction of laminin alpha2 immunolabeling, either on muscle sections or immunoblotting alone. CONCLUSIONS: LGMD2I due to FKRP mutations appears to be a relatively common cause of LGMD, with respiratory and cardiac failure as prominent complications.

Maintaining teeth in their corrected positions following orthodontic treatment can be extremely challenging. Teeth have a tendency to move back towards the original malocclusion as a result of periodontal, gingival, occlusal and growth related factors. However, tooth movement can also occur as a result of normal age changes. Because orthodontics is unable to predict which patients are at risk of relapse, those which will remain stable and the extent of relapse that will occur in the long-term, clinicians need to treat all patients as if they have a high potential to relapse. To reduce this risk, long term retention is advocated. This can be a significant commitment for patients, and so retention and the potential for relapse must form a key part of the informed consent process prior to orthodontic treatment. It is vital that patients are made fully aware of their responsibilities in committing to wear retainers as prescribed in order to reduce the chance of relapse. If patients are unable or unwilling to comply as prescribed, they must be prepared to accept that there will be tooth positional changes following treatment. There is currently insufficient high quality evidence regarding the best type of retention or retention regimen, and so each clinician's approach will be affected by their personal, clinical experience and expertise, and guided by their patients' expectations and circumstances.

OBJECTIVE: Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient, reduces emotional stress for the care giver, and lessens the need for community support. DESIGN: Stratified, randomised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist. The six month assessment results are reported in this paper. SUBJECTS: Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability. SETTING: Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists. MAIN OUTCOME MEASURES: Barthel index, functional ambulatory categories, Motor Club assessment, Frenchay activities index, and Nottingham health profile were used. Carers' stress was indicated by the general health questionnaire. Treatment given and community care provided were recorded. RESULTS: Of 124 patients recruited, 108 were available for reassessment at six months. Both treatment groups had significantly improved in functional abilities between discharge and six months. The improvements were significantly greater for patients treated at home (Mann-Whitney test; Barthel index, median difference 2 (95% confidence interval 0 to 3) p = 0.01; Motor Club assessment, median difference 2 (1 to 5), p = 0.01). The home treated patients received less treatment (median difference 16 (11 to 21) treatments, p less than 0.001). More than a third of patients in both groups showed depressed mood, and a quarter of care givers were emotionally distressed. CONCLUSIONS: Home physiotherapy seems to be slightly more effective and more resource efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients. New strategies are needed to address psychosocial function for both patients and care givers.

A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed.

OBJECTIVE: Psoriatic arthritis (PsA) is characterized by inflammatory arthritis in the presence of psoriasis. Certain clinical features help characterize this disorder, one of which is dactylitis. Hitherto an instrument for quantifying dactylitis has not been developed. METHODS: A dactylitis score sheet was developed. The score is a function of finger circumference and tenderness, assessed and summed across all dactylitic digits. Initial results were obtained on a small sample of patients attending clinics. Inter and intraobserver agreement on the presence of dactylitis using kappa agreement statistics, and the validity and reliability of the instrument, using intraclass correlation coefficients (ICC), were assessed in a further group of 7 patients with PsA. RESULTS: Tender dactylitis was deemed present in 74 digits out of a total of 280 (140 digits on each occasion). Kappa agreement scores for the presence of tender dactylitis were poor to good, both within and between observers (0.25 to 0.89 between observers and 0.29 to 0.91 within observers). Agreement scores for non-tender dactylitis were poor (0.01 to 0.66 between observers and 0.01 to 0.59 within-observer agreement). The new dactylitis instrument was simple and easy to administer and was found to measure appropriate scores in patients with different severity of dactylitis. Inter and intraobserver agreement was good (interobserver ICC 0.90, 95% CI 0.74-0.98; intraobserver ICC 0.84, 95% CI 0.71-0.92). Intraobserver ICC improved but interobserver ICC deteriorated by rating simply presence or absence, rather than a 4 point grade, of tenderness. CONCLUSION: A new method for quantifying dactylitis based on digital circumference and tenderness has been described. This instrument has shown good inter and intraobserver reliability. Further studies of responsiveness are now required.

OBJECTIVE: To evaluate whether patients who had received early class III protraction facemask treatment were less likely to need orthognathic surgery compared with untreated controls. This paper is a 6-year follow-up of a previous clinical trial. DESIGN: Multi-centre 2-arm parallel randomized controlled trial. SETTING: Eight United Kingdom hospital orthodontic departments. PARTICIPANTS: Seventy three 7- to 9-year-old children. METHOD: Patients were randomly allocated, stratified for gender, into an early class III protraction facemask group (PFG) (n = 35) and a control/no treatment group (CG) (n = 38). The primary outcome, need for orthognathic surgery was assessed by panel consensus. Secondary outcomes were changed in skeletal pattern, overjet, Peer Assessment Rating (PAR), self-esteem and the oral aesthetic impact of malocclusion. The data were compared between baseline (DC1) and 6-year follow-up (DC4). A per-protocol analysis was carried out with n = 32 in the CG and n = 33 in the PFG. RESULTS: Thirty six percent of the PFG needed orthognathic surgery, compared with 66% of the CG (P = 0.027). The odds of needing surgery was 3.5 times more likely when protraction facemask treatment was not used (odds ratio = 3.34 95% CI 1.21-9.24). The PFG exhibited a clockwise rotation and the CG an anti-clockwise rotation in the maxilla (regression coefficient 8.24 (SE 0.75); 95% CI 6.73-9.75; P < 0.001) and the mandible (regression coefficient 6.72 (SE 0.73); 95% CI 5.27-8.18; P < 0.001). Sixty eight per cent of the PFG maintained a positive overjet at 6-year follow-up. There were no statistically significant differences between the PFG and CG for skeletal/occlusal improvement, self-esteem or oral aesthetic impact. CONCLUSIONS: Early class III protraction facemask treatment reduces the need for orthognathic surgery. However, this effect cannot be explained by the maintenance of skeletal cephalometric change.

OBJECTIVE: To evaluate the effectiveness of different retention strategies used to maintain tooth position after treatment by orthodontic appliances. DATA SOURCES: The search strategy was carried out according to the standard Cochrane systematic review methodology. The following databases were searched for randomized clinical trials (RCT) or controlled clinical trials (CCT): Cochrane Oral Health Group Trials Register, Cochrane Clinical Trials Register, MEDLINE and EMBASE. No language restrictions were applied. Authors of trials were contacted to identify unpublished trials. Inclusion and exclusion criteria were applied when considering the studies to be included and a quality assessment made for each paper. DATA SELECTION: The primary outcome was the amount of relapse. Secondary outcomes were survival of retainers, adverse effects on oral health and patient satisfaction. DATA EXTRACTION: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two reviewers. Five studies (2 RCTs and 3 CCTs) fulfilled the inclusion criteria. DATA SYNTHESIS: There was evidence, based on data from one trial, that there was a statistically significant increase in stability in both the mandibular (P<0.001) and maxillary anterior segments (P<0.001) when the CSF (circumferential supracrestal fiberotomy) was used in conjunction with a Hawley retainer, compared with a Hawley retainer alone. However, this evidence may be unreliable due to flaws in the study design. There was also weak, unreliable evidence that teeth settle quicker with a Hawley retainer than with a clear overlay retainer after 3 months. CONCLUSIONS: There is currently insufficient evidence on which to base the clinical practice of orthodontic retention.