A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis

Background \ud Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. \ud \ud Methods \ud One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. \ud \ud Results \ud Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. \ud \ud Conclusion \ud Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores

Effect of time and day of admission on hospital care quality for patients with chronic obstructive pulmonary disease exacerbation in England and Wales: single cohort study

OBJECTIVE: To evaluate if observed increased weekend mortality was associated with poorer quality of care for patients admitted to hospital with chronic obstructive pulmonary disease (COPD) exacerbation. DESIGN: Prospective case ascertainment cohort study. SETTING: 199 acute hospitals in England and Wales, UK. PARTICIPANTS: Consecutive COPD admissions, excluding subsequent readmissions, from 1 February to 30 April 2014 of whom 13 414 cases were entered into the study. MAIN OUTCOMES: Process of care mapped to the National Institute for Health and Care Excellence clinical quality standards, access to specialist respiratory teams and facilities, mortality and length of stay, related to time and day of the week of admission. RESULTS: Mortality was higher for weekend admissions (unadjusted OR 1.20, 95% CI 1.00 to 1.43), and for case-mix adjusted weekend mortality when calculated for admissions Friday morning through to Monday night (adjusted OR 1.19, 95% CI 1.00 to 1.43). Median time to death was 6 days. Some clinical processes were poorer on Mondays and during normal working hours but not weekends or out of hours. Specialist respiratory care was less available and less prompt for Friday and Saturday admissions. Admission to a specialist ward or high dependency unit was less likely on a Saturday or Sunday. CONCLUSIONS: Increased mortality observed in weekend admissions is not easily explained by deficiencies in early clinical guideline care. Further study of out-of-hospital factors, specialty care and deaths later in the admission are required if effective interventions are to be made to reduce variation by day of the week of admission

Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot

Use, utility and methods of telehealth for patients with COPD in England and Wales: a healthcare provider survey

INTRODUCTION: Although the effectiveness of domiciliary monitoring (telehealth) to improve outcomes in chronic obstructive pulmonary disease (COPD) is controversial, it is being used in the National Health Service (NHS). AIM: To explore the use of teleheath for COPD across England and Wales, to assess the perceptions of clinicians employing telehealth in COPD and to summarise the techniques that have been used by healthcare providers to personalise alarm limits for patients with COPD enrolled in telehealth programmes. METHODS: A cross-sectional survey consisting of 14 questions was sent to 230 COPD community services in England and Wales. Questions were designed to cover five aspects of telehealth in COPD: purpose of use, equipment type, clinician perceptions, variables monitored and personalisation of alarm limits. RESULTS: 65 participants completed the survey from 52 different NHS Trusts. 46% of Trusts had used telehealth for COPD, and currently, 31% still provided telehealth services to patients with COPD. Telehealth is most commonly used for baseline monitoring and to allow early detection of exacerbations, with 54% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate and breathlessness. A variety of methods were used to set alarm limits with the majority of respondents believing that at least 40% of alarms were false. CONCLUSION: Around one-third of responded community COPD services are using telehealth, believing it to be effective without robust evidence, with a variety of variables monitored, a variety of hardware and varying techniques to set alarm limits with high false alarm frequencies

Bedside rationing by general practitioners: A postal survey in the Danish public healthcare system

<p>Abstract</p> <p>Background</p> <p>It is ethically controversial whether medical doctors are morally permitted to ration the care of their patients at the bedside. To explore whether general practitioners in fact do ration in this manner we conducted a study within primary care in the Danish public healthcare system. The purpose of the study was to measure the extent to which general practitioners (GPs) would be willing to factor in cost-quality trade-offs when prescribing medicine, and to discover whether, and if so to what extent, they believe that patients should be informed about this.</p> <p>Methods</p> <p>Postal survey of 600 randomly selected Danish GPs, of which 330 responded to the questionnaire. The Statistical Package for the Social Sciences (SPSS, version 14.0) was used to produce general descriptive statistics. Significance was calculated with the McNemar and the chi-square test. The main outcome measures of the study were twofold: an assessment of the proportion of GPs who, in a mainly hypothetical setting, would consider cost-quality trade-offs relevant to their clinical decision-making given their economic impact on the healthcare system; and a measure of the extent to which they would disclose this information to patients.</p> <p>Results</p> <p>In the hypothetical setting 95% of GPs considered cost-quality trade-offs relevant to their clinical decision-making given the economic impact of such trade-offs on the healthcare system. In all 90% stated that this consideration had been relevant in clinical decision-making within the last month. In the hypothetical setting 55% would inform their patients that they considered a cost-quality trade-off relevant to their clinical decisions given the economic impact of such trade-offs on the healthcare system. The most common reason (68%) given for not wanting to inform patients about this matter was the belief that the information would not prove useful to patients. In the hypothetical setting cost-quality trade-offs were considered relevant significantly more often in connection with concerns about costs to the patient (86%) than they were in connection with concerns about costs to the healthcare system (55%; p < 0.001).</p> <p>Conclusion</p> <p>Although readiness to consider cost-quality trade-offs relevant to clinical decisions is prevalent among GPs in Denmark, only half of GPs would disclose to patients that they consider this relevant to their clinical decision-making. The results of this study raise two important ethical problems. First, under Danish law physicians are required to inform patients about all equal treatments. The fact that only a few GPs would inform their patients about all of the relevant treatments therefore seems to contravene Danish law. Second, it is ethically controversial that physicians act as economic gatekeepers.</p

The role of TcdB and TccC subunits in secretion of the photorhabdus Tcd toxin complex

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5:1:1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

The diversity of reproductive parasites among arthropods: Wolbachia do not walk alone

<p>Abstract</p> <p>Background</p> <p>Inherited bacteria have come to be recognised as important components of arthropod biology. In addition to mutualistic symbioses, a range of other inherited bacteria are known to act either as reproductive parasites or as secondary symbionts. Whilst the incidence of the α-proteobacterium <it>Wolbachia </it>is relatively well established, the current knowledge of other inherited bacteria is much weaker. Here, we tested 136 arthropod species for a range of inherited bacteria known to demonstrate reproductive parasitism, sampling each species more intensively than in past surveys.</p> <p>Results</p> <p>The inclusion of inherited bacteria other than <it>Wolbachia </it>increased the number of infections recorded in our sample from 33 to 57, and the proportion of species infected from 22.8% to 32.4%. Thus, whilst <it>Wolbachia </it>remained the dominant inherited bacterium, it alone was responsible for around half of all inherited infections of the bacteria sampled, with members of the <it>Cardinium</it>, <it>Arsenophonus </it>and <it>Spiroplasma ixodetis </it>clades each occurring in 4% to 7% of all species. The observation that infection was sometimes rare within host populations, and that there was variation in presence of symbionts between populations indicates that our survey will itself underscore incidence.</p> <p>Conclusion</p> <p>This extensive survey demonstrates that at least a third of arthropod species are infected by a diverse assemblage of maternally inherited bacteria that are likely to strongly influence their hosts' biology, and indicates an urgent need to establish the nature of the interaction between non-<it>Wolbachia </it>bacteria and their hosts.</p