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.
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.
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.
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.
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.
The aim of this pilot study was to compare the effects of equimolar doses of hypertonic saline and dextran solution (HSD, Rescueflow) with 20% mannitol solution for reduction of increased ...intracranial pressure.
Prospective, randomized, controlled, crossover trial in the intensive care unit of a large teaching hospital.
Academic hospital and tertiary referral center for neuroscience.
Nine patients with an intracranial pressure of >20 mm Hg were recruited and received two treatments of each, HSD and 20% mannitol, in a randomized order.
Equimolar, rapid intravenous infusions of either 200 mL of 20% mannitol or 100 mL of 7.5% saline and 6% dextran-70 solution (HSD) over 5 mins.
Intracranial pressure, blood pressure, serum and urine sodium and osmolality, and urine output.
Treatments reduced intracranial pressure with both mannitol (median decrease, 7.5 mm Hg, 95% confidence interval, 5.8-11.8) and HSD (median decrease, 13 mm Hg; 95% confidence interval, 11.5-17.3). HSD caused a significantly greater decrease in intracranial pressure than mannitol (p = .044). HSD had a longer duration of effect than mannitol (p = .044).
When given in an equimolar, rapid, intravenous infusion, HSD reduces intracranial pressure more effectively than mannitol.
Background
Despite rehabilitation being increasingly advocated for people living with incurable cancer, there is limited evidence supporting efficacy or component parts. The progressive decline in ...function and nutritional in this population would support an approach that targets these factors. This trial aimed to assess the feasibility of an exercise and nutrition based rehabilitation programme in people with incurable cancer.
Methods
We randomized community dwelling adults with incurable cancer to either a personalized exercise and nutrition based programme (experimental arm) or standard care (control arm) for 8 weeks. Endpoints included feasibility, quality of life, physical activity (step count), and body weight. Qualitative and health economic analyses were also included.
Results
Forty‐five patients were recruited (23 experimental arm, 22 control arm). There were 26 men (58%), and the median age was 78 years (IQR 69–84). At baseline, the median BMI was 26 kg/m2 (IQR: 22–29), and median weight loss in the previous 6 months was 5% (IQR: −12% to 0%). Adherence to the experimental arm was >80% in 16/21 (76%) patients. There was no statistically significant difference in the following between trial arms: step count − median % change from baseline to endpoint, per trial arm (experimental −18.5% IQR: −61 to 65, control 5% IQR: −32 to 50, P = 0.548); weight − median % change from baseline to endpoint, per trial arm (experimental 1%IQR: −3 to 3, control −0.5% IQR: −3 to 1, P = 0.184); overall quality of life − median % change from baseline to endpoint, per trial arm (experimental 0% IQR: −20 to 19, control 0% IQR: −23 to 33, P = 0.846). Qualitative findings observed themes of capability, opportunity, and motivation amongst patients in the experimental arm. The mean incremental cost of the experimental arm versus control was £‐319.51 CI −7593.53 to 6581.91, suggesting the experimental arm was less costly.
Conclusions
An exercise and nutritional rehabilitation intervention is feasible and has potential benefits for people with incurable cancer. A larger trial is now warranted to test the efficacy of this approach.
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