Numerous viruses can cause upper respiratory tract infections. They often precede serious lower respiratory tract infections. Each virus has a seasonal pattern, with peaks in activity in different ...seasons. We examined the effects of daily local meteorological data (temperature, relative humidity, "humidity-range" and dew point) from Edinburgh, Scotland on the seasonal variations in viral transmission. We identified the seasonality of rhinovirus, adenovirus, influenza A and B viruses, human parainfluenza viruses 1-3 (HPIV), respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) from the 52060 respiratory samples tested between 2009 and 2015 and then confirmed the same by a generalised linear model. We also investigated the relationship between meteorological factors and viral seasonality. Non-enveloped viruses were present throughout the year. Following logistic regression adenovirus, influenza viruses A, B, RSV and HMPV preferred low temperatures; RSV and influenza A virus preferred a narrow "humidity-range" and HPIV type 3 preferred the season with lower humidity. A change (i.e. increase or decrease) in specific meteorological factors is associated with an increase in activity of specific viruses at certain times of the year.
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults ...with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 10
, 10
or up to 10
cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.
Optimization of technical parameters that influence the performance of human papillomavirus (HPV) testing on self-taken samples is important. Here, the authors assessed the impact of resuspension ...volume on the detection of HPV using four validated HPV assays. Two self-sampling devices, FLOQSwabs
and Evalyn
Brushes, were inoculated with dilutions of HPV-16-positive cell line, then resuspended in various volumes of ThinPrep. The influence of vortexing during resuspension was also assessed. At target concentrations around the assay cutoff, larger volumes led to decreased HPV detection. Interestingly, the effect(s) of vortexing differed by the self-sampling device. Resuspension in 5 ml or less may maximize the detection of HPV sequences. Using a proxy of clinical material, the current observations underline the importance of optimizing preanalytical laboratory processes to support high-quality HPV testing of self-samples.
Two commonly used sampling devices, FLOQSwab
and Evalyn
Brush, were used alongside four clinically validated HPV detection assays, Anyplex™ II HPV 28, Aptima HPV, Alinity m HR HPV and cobas
8800 HPV. The sampling device was submerged into suspensions of an HPV-16-containing cell line (1–2 copies of HPV-16 per cell) at known concentrations, and then resuspended in various volumes of ThinPrep. Cellular concentrations ranged from 10
cells/ml to 10
cells/ml, and resuspension volumes were either 3 ml, 5 ml, 10 ml or 20 ml, to reflect the range of volumes found in the literature. The impact of using a vortex at the time of resuspension was also assessed.
The modified Rankin Scale (mRS) is the most common outcome measure in large randomized controlled trials in stroke. We tested 2 postal mRS questionnaires and a telephone questionnaire to determine ...completion rates and intermodality agreement.
We sent postal questionnaires containing 2 versions of the mRS to surviving stroke patients. One version, tick box, involved the patient/proxy ticking 1 of the 5 descriptions equating to mRS scores; the other, the simplified modified Rankin questionnaire (smRSq), included 5 questions with yes/no responses from which the mRS is derived. We performed a semistructured telephone interview to consenting respondents, blinded to postal responses, to assign an mRS. We compared the mRS obtained by these different methods.
We sent questionnaires to 343 of 356 surviving patients (96%) and received 225 responses (66%). The mRS could not be derived in 27 respondents (12%) and 10 respondents (4%) on the tick box and smRSq, respectively (difference in proportion, 8% 95% CI, 3-13. One hundred three of 190 respondents (54%) to the postal questionnaire agreed on the tick box versus smRSq version (κ=0.44 0.38, 0.50). Agreements between the tick box versus telephone and smRSq versus telephone were 57% (ie, 87/152, κ=0.47 0.40, 0.55, and 64% (ie, 104/161, κ=0.55 0.47, 0.62, respectively.
In large studies where face-to-face assessment of mRS is impractical, a postal smRSq with telephone follow-up to nonresponders will achieve higher levels of follow-up than will the tick box version and also good levels of intermodality agreement with least risk of bias.
BackgroundThe prevalence and risk factors for recurrent instability and functional impairment following a primary glenohumeral dislocation remain poorly defined in younger patients. We performed a ...prospective cohort study to evaluate these outcomes. We also aimed to produce guidelines for the design of future clinical trials, assessing the efficacy of interventions designed to improve the outcome after a primary dislocation.MethodsWe performed a prospective cohort study of 252 patients ranging from fifteen to thirty-five years old who sustained an anterior glenohumeral dislocation and were treated with sling immobilization, followed by a physical therapy program. Patients received regular clinical follow-up to assess whether recurrent instability had developed. Functional assessments were made and were compared for two subgroupsthose who had not had instability develop and those who had received operative stabilization to treat recurrent instability.ResultsOn survival analysis, instability developed in 55.7% of the shoulders within the first two years after the primary dislocation and increased to 66.8% by the fifth year. The younger male patients were most at risk of instability, and 86.7% of all of the patients known to have recurrent instability had this complication develop within the first two years. A small but measurable degree of functional impairment was present at two years after the initial dislocation in most patients. Sample-size calculations revealed that a relatively small number of patients with a primary dislocation would be required in future clinical trials examining the effects of interventions designed to reduce the prevalence of recurrent instability and improve the functional outcome.ConclusionsRecurrent instability and deficits of shoulder function are common after primary nonoperative treatment of an anterior shoulder dislocation. There is substantial variation in the risk of instability, with younger males having the highest risk and females having a much lower risk. Future clinical trials to evaluate primary interventions should evaluate the prevalence of recurrent instability and functional deficits, with use of an assessment tool specifically for shoulder instability, during the first two years after the initial dislocation.Level of EvidencePrognostic Level I. See Instructions to Authors for a complete description of levels of evidence.
Venous thromboembolism (VTE) is a common cause of death and morbidity in stroke patients. There are few data concerning the effectiveness of intermittent pneumatic compression (IPC) in treating ...patients with stroke.
To establish whether or not the application of IPC to the legs of immobile stroke patients reduced their risk of deep vein thrombosis (DVT).
Clots in Legs Or sTockings after Stroke (CLOTS) 3 was a multicentre, parallel-group, randomised controlled trial which allocated patients via a central randomisation system to IPC or no IPC. A technician blinded to treatment allocation performed compression duplex ultrasound (CDU) of both legs at 7-10 days and 25-30 days after enrolment. We followed up patients for 6 months to determine survival and later symptomatic VTE. Patients were analysed according to their treatment allocation.
We enrolled 2876 patients in 94 UK hospitals between 8 December 2008 and 6 September 2012.
patients admitted to hospital within 3 days of acute stroke and who were immobile on the day of admission (day 0) to day 3.
age < 16 years; subarachnoid haemorrhage; and contra-indications to IPC including dermatitis, leg ulcers, severe oedema, severe peripheral vascular disease and congestive cardiac failure.
Participants were allocated to routine care or routine care plus IPC for 30 days, or until earlier discharge or walking independently.
The primary outcome was DVT in popliteal or femoral veins, detected on a screening CDU, or any symptomatic DVT in the proximal veins, confirmed by imaging, within 30 days of randomisation. The secondary outcomes included death, any DVTs, symptomatic DVTs, pulmonary emboli, skin breaks on the legs, falls with injury or fractures and duration of IPC use occurring within 30 days of randomisation and survival, symptomatic VTE, disability (as measured by the Oxford Handicap Scale), quality of life (as measured by the European Quality of Life-5 Dimensions 3 Level questionnaire) and length of initial hospital stay measured 6 months after randomisation.
We allocated 1438 patients to IPC and 1438 to no IPC. The primary outcome occurred in 122 (8.5%) of 1438 patients allocated to IPC and 174 (12.1%) of 1438 patients allocated to no IPC, giving an absolute reduction in risk of 3.6% 95% confidence interval (CI) 1.4% to 5.8% and a relative risk reduction of 0.69 (95% CI 0.55 to 0.86). After excluding 323 patients who died prior to any primary outcome and 41 who had no screening CDU, the primary outcome occurred in 122 of 1267 IPC participants compared with 174 of 1245 no-IPC participants, giving an adjusted odds ratio of 0.65 (95% CI 0.51 to 0.84; p = 0.001). Secondary outcomes in IPC compared with no-IPC participants were death in the treatment period in 156 (10.8%) versus 189 (13.1%) (p = 0.058); skin breaks in 44 (3.1%) versus 20 (1.4%) (p = 0.002); and falls with injury in 33 (2.3%) versus 24 (1.7%) (p = 0.221). Among patients treated with IPC, there was a statistically significant improvement in survival to 6 months (hazard ratio 0.86, 95% CI 0.73 to 0.99; p = 0.042), but no improvement in disability. The direct cost of preventing a DVT was £1282 per event (95% CI £785 to £3077).
IPC is an effective and inexpensive method of reducing the risk of DVT and improving survival in immobile stroke patients.
Further research should test whether or not IPC improves survival in other groups of high-risk hospitalised medical patients. In addition, research into methods to improve adherence to IPC might increase the benefits of IPC in stroke patients.
Current Controlled Trials ISRCTN93529999.
The start-up phase of the trial (December 2008-March 2010) was funded by the Chief Scientist Office of the Scottish Government (reference number CZH/4/417). The main phase of the trial was funded by the National Institute for Health Research Health Technology Assessment programme (reference number 08/14/03). Covidien Ltd (Mansfield, MA, USA) lent its Kendall SCD™ Express sequential compression system controllers to the 105 centres involved in the trial and donated supplies of its sleeves. It also provided logistical help in keeping our centres supplied with sleeves and training materials relevant to the use of their devices. Recruitment and follow-up were supported by the National Institute for Health Research-funded UK Stroke Research Network and by the Scottish Stroke Research Network, which was supported by NHS Research Scotland.
To summarize and compare the effectiveness of pharmacological thromboprophylaxis to pneumatic compression devices (PCD) for the prevention of venous thromboembolism in patients with acute ...intracerebral hemorrhage.
MEDLINE, PUBMED, EMBASE, and CENTRAL were systematically searched to identify randomized and non-randomized studies that compared each intervention directly to each other or against a common control (hydration, anti-platelet agents, stockings) in adults with acute spontaneous intracerebral hemorrhage. Two investigators independently screened the studies, extracted data, and appraised risk of bias. Studies with a high risk of bias were excluded from our final analysis. The primary outcome was the occurrence of venous thromboembolism (proximal deep vein thrombosis or pulmonary embolism) in the first 30 days.
8,739 articles were screened; four articles, all randomized control trials, met eligibility criteria. Bayesian network meta-analysis was performed to calculate risk estimates using both fixed and random effects analyses. 607 patients were included in the network analysis. PCD were associated with a significant decrease in venous thromboembolism compared to control (OR: 0.43, 95% Credible Limits CrI: 0.23-0.80). We did not find evidence of statistically significant differences between pharmacological thromboprophylaxis and control (OR: 0.93, 95% CrI: 0.19-4.37) or between PCD and pharmacological thromboprophylaxis (OR: 0.47, 95% CrI: 0.09-2.54).
PCDs are superior to control interventions, but meaningful comparisons with pharmacotherapy are not possible due to a lack of data. This requires further exploration via large pragmatic clinical trials.
PROSPERO: CRD42018090960.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are limited data reporting the outcome of patients with non-operatively managed medial malleolus fractures compared to those treated surgically in the presence of fibular stabilisation for ...unstable fractures of the ankle. Conservative management could result in fewer complications, reduced surgical time and lower cost. The purpose of this study is to determine if any difference exists in patient reported and surgical outcomes 1 year after surgery between operative and non-operative treatment of medial malleolar fractures in combination with stabilisation of the lateral malleolus.
This is a single-centre, prospective, randomised controlled trial that aims to randomise 154 participants with an unstable ankle fracture to 'non-fixation' (n = 77) or 'fixation' (n = 77) of an associated well-reduced medial malleolus fracture following fibular stabilisation. The study will include patients ≥ 16 years of age with a closed bimalleolar or trimalleolar ankle fracture who are able to consent, complete questionnaires in the English language, and complete follow-up over a 1-year period. Randomisation will occur intra-operatively when the medial malleolus fracture is deemed 'well-reduced', with 2 mm or less of fluoroscopic displacement. The technique for fixation of both the medial and lateral malleoli is at the discretion of the operating surgeon. Patient-reported, observer-rated, and radiographic assessments will be collected at baseline and then at the following post-operative assessment points: 2 weeks, 6 weeks and 1 year. Postal questionnaire outcome data will be collected at 3 and 6 months. The primary outcome measure will be the Olerud Molander Ankle Score (OMAS) at 1 year following surgery. Secondary outcome measures will include the Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol-5D (EQ-5D), pain, treatment satisfaction, time to return to activity, operative tourniquet time, and complications.
There is only one previous randomised trial comparing non-fixation with fixation of associated medial malleolus fractures but that was limited by the lack of baseline patient-reported outcome data and an inferior sample size. This current prospective trial aims to provide high-quality evidence regarding the requirement for medial malleolar fixation in unstable ankle fractures.
ClinicalTrials.gov, NCT03362229 . Registered retrospectively on 5 December 2017.
Our Cochrane review of selective serotonin inhibitors for stroke recovery indicated that fluoxetine may improve functional recovery, but the trials were small and most were at high risk of bias.
The ...Fluoxetine Or Control Under Supervision (FOCUS) trial tested the hypothesis that fluoxetine improves recovery after stroke.
The FOCUS trial was a pragmatic, multicentre, parallel-group, individually randomised, placebo-controlled trial.
This trial took place in 103 UK hospitals.
Patients were eligible if they were aged ≥ 18 years, had a clinical stroke diagnosis, with focal neurological deficits, between 2 and 15 days after onset.
Patients were randomly allocated 20 mg of fluoxetine once per day or the matching placebo for 6 months via a web-based system using a minimisation algorithm.
The primary outcome was the modified Rankin Scale at 6 months. Patients, carers, health-care staff and the trial team were masked to treatment allocation. Outcome was assessed at 6 and 12 months after randomisation. Patients were analysed by their treatment allocation as specified in a published statistical analysis plan.
Between 10 September 2012 and 31 March 2017, we recruited 3127 patients, 1564 of whom were allocated fluoxetine and 1563 of whom were allocated placebo. The modified Rankin Scale score at 6 months was available for 1553 out of 1564 (99.3%) of those allocated fluoxetine and 1553 out of 1563 (99.4%) of those allocated placebo. The distribution across modified Rankin Scale categories at 6 months was similar in the two groups (common odds ratio adjusted for minimisation variables 0.951, 95% confidence interval 0.839 to 1.079;
= 0.439). Compared with placebo, patients who were allocated fluoxetine were less likely to develop a new episode of depression by 6 months 210 (13.0%) vs. 269 (16.9%), difference -3.78%, 95% confidence interval -1.26% to -6.30%;
= 0.003, but had more bone fractures 45 (2.9%) vs. 23 (1.5%), difference 1.41%, 95% confidence interval 0.38% to 2.43%;
= 0.007. There were no statistically significant differences in any other recorded events at 6 or 12 months. Health economic analyses showed no differences between groups in health-related quality of life, hospital bed usage or health-care costs.
Some non-adherence to trial medication, lack of face-to-face assessment of neurological status at follow-up and lack of formal psychiatric diagnosis during follow-up.
20 mg of fluoxetine daily for 6 months after acute stroke did not improve patients' functional outcome but decreased the occurrence of depression and increased the risk of fractures. These data inform decisions about using fluoxetine after stroke to improve functional outcome or to prevent or treat mood disorders. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) (Australasia/Vietnam) and Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS) (Sweden) trials recruited an additional 2780 patients and will report their results in 2020. These three trials have an almost identical protocol, which was collaboratively developed. Our planned individual patient data meta-analysis will provide more precise estimates of the effects of fluoxetine after stroke and indicate whether or not effects vary depending on patients' characteristics and health-care setting.
Current Controlled Trials ISRCTN83290762.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 24, No. 22. See the NIHR Journals Library website for further project information. The Stroke Association (reference TSA 2011101) funded the start-up phase.
The long-term risk of stroke or myocardial infarction (MI) in patients with minor neurological symptoms who are not clinically diagnosed with transient ischaemic attack (TIA) or minor stroke is ...uncertain.
We used data from a rapid access clinic for patients with suspected TIA or minor stroke and follow-up from four overlapping data sources for a diagnosis of ischaemic or haemorrhagic stroke, MI, major haemorrhage and death. We identified patients with and without a clinical diagnosis of TIA or minor stroke. We estimated hazard ratios of stroke, MI, major haemorrhage and death in early and late time periods.
5,997 patients were seen from 2005-2013, who were diagnosed with TIA or minor stroke (n = 3604, 60%) or with other diagnoses (n = 2392, 40%). By 5 years the proportion of patients who had a subsequent ischaemic stroke or MI, in patients with a clinical diagnosis of minor stroke or TIA was 19% 95% confidence interval (CI): 17-20%, and in patients with other diagnoses was 10% (95%CI: 8-15%). Patients with clinical diagnosis of TIA or minor stroke had three times the hazard of stroke or MI compared to patients with other diagnoses hazard ratio (HR)2.83 95%CI:2.13-3.76, adjusted age and sex by 90 days post-event; however from 90 days to end of follow up, this difference was attenuated (HR 1.52, 95%CI:1.25-1.86). Older patients and those who had a history of vascular disease had a high risk of stroke or MI, whether or not they were diagnosed with minor stroke or TIA.
Careful attention to vascular risk factors in patients presenting with transient or minor neurological symptoms not thought to be due to stroke or TIA is justified, particularly those who are older or have a history of vascular disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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