NIHR Signal: Switching to oral antibiotics early for bone and joint infections gave similar results to continuing intravenous therapy

NIHR | April 2019 | Switching to oral antibiotics early for bone and joint infections gave similar results to continuing intravenous therapy

Although current practice suggests antibiotics should be given intravenously (IV) for bone and joint infections, for at least six weeks, a large NIHR-funded UK trial challenges this assumption. In the trial participants were randomised to oral antibiotics seven days after initial surgical or IV antibiotic treatment. 222 participants (average age 36 years)  with hip pain and limited movement due to femoro-acetabular (hip) impingement but without a diagnosis of osteoarthritis.  Fifty per cent of the people who had surgery had significant benefit compared with a third of those having physiotherapy.

The randomised controlled trial had more than 1000 participants recruited from 26 centres. Patients were enrolled within seven days of either surgery or IV antibiotics to treat infection in the bone or joint. Causes ranged from a joint replacement infection to diabetes complications. Most had Staphylococcus aureus infections, and over 90% had initial surgical treatment.

Both the IV and the oral group received antibiotics for at least six weeks. In accordance with usual practice, the IV group could also be given oral antibiotics, such as rifampicin. Similarly, the oral group could have up to five consecutive days of IV antibiotics for unrelated infections; over 80% of the oral group started with IV antibiotics. The primary outcome was treatment failure within one year (Source: NIHR).

Read the Signal in full from NIHR 

Full reference: Palmer, A. J. et al |2019| Arthroscopic hip surgery compared with physiotherapy and activity modification for the treatment of symptomatic femoroacetabular impingement: multicentre randomised controlled trial| BMJ |364|l185.

Abstract

BACKGROUND The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points, indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant. Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.3% vs. 1.0%). CONCLUSIONS Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.)

 

 

Full article available through Athens, Rotherham NHS staff can contact the Library for access

Diet and colorectal cancer in UK Biobank: a prospective study

Bradbury, K.E.,  Murphy, N., Key, T. | 2019| Diet and colorectal cancer in UK Biobank: a prospective study|  International Journal of Epidemiology| dyz064| https://doi.org/10.1093/ije/dyz064

A research team behind a study into diet and the impact of diet on colorectal cancer used data from the UK Biobank research project in conjunction with  questionnaires to learn about the dietary habits of men and women aged between 40- 69 years and their potential risk of developing colorectal cancer. 
At follow up five years later the participants who had consumed (on average) 76g of red meat, compared to 21g, had a higher risk of developing cancer than other participants.

Participants who ate red meat on four or more occasions a week had a fifth increased risk of developing colorectal cancer compared with subjects who ate red meat twice weekly. 
Subjects who consumed the most wholegrains had a 14% lower risk of developing  colorectal cancer.
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Key Messages
  • Previous studies have found an increased risk of colorectal cancer in those with high intakes of red and processed meat. Most previous studies collected information on dietary intakes during the 1990s or earlier and patterns in meat consumption have since changed.
  • In addition, few studies have used re-measured intakes to reduce the impact of measurement error, and to quantify the amount of red and processed meat that is associated with an increased risk. Measurement error generally biases the associations towards the null value; the associations observed in previous studies that did not re-measure intakes may be underestimated.
  • Our study found that people who were consuming red and processed meat four or more times per week, had a 20% increased risk of colorectal cancer compared with those who were consuming red and processed meat less than twice a week.

Abstract

Background

Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s.

Methods

We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40–69 years at recruitment (2006–10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time.

Results

During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% lower risk of colorectal cancer. Alcohol was associated with an 8% higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk.

Conclusions

Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (less than or equal to 90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk.

 

The article is available to read in full in the International Journal of Epidemiology 

In the news:

The Independent Even government guideline amounts of red meat and bacon increase risk of bowel cancer, study finds 

The Guardian Even moderate intake of red meat raises cancer risk, study finds

BBC News A rasher of bacon a day ‘ups cancer risk’ 

JAMA: Trial finds workplace wellness program has no significant effects on clinical measures of health, health care spending and utilization, or employment outcomes

Song, Z., &  Baicker, K. | 2019| Effect of a Workplace Wellness Program on Employee Health and Economic OutcomesA Randomized Clinical Trial | JAMA |321| 15 | P.1491-1501. doi:10.1001/jama.2019.3307

A US study used a randomised controlled trial (RCT) to evaluate a multicomponent workplace wellness program resembling programs offered by US employers

Using data from 160 workplaces the research team 20 randomly selected treatment worksites which received a wellness program which 8 modules focused on nutrition, physical activity, stress reduction, and related topics implemented by registered dietitians; the 140 randomly selected as control worksites received no wellness program.

 

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Key Points

Question  What is the effect of a multicomponent workplace wellness program on health and economic outcomes?

Findings  In this cluster randomized trial involving 32 974 employees at a large US warehouse retail company, worksites with the wellness program had an 8.3-percentage point higher rate of employees who reported engaging in regular exercise and a 13.6-percentage point higher rate of employees who reported actively managing their weight, but there were no significant differences in other self-reported health and behaviors; clinical markers of health; health care spending or utilization; or absenteeism, tenure, or job performance after 18 months.

Meaning  Employees exposed to a workplace wellness program reported significantly greater rates of some positive health behaviors compared with those who were not exposed, but there were no significant effects on clinical measures of health, health care spending and utilization, or employment outcomes after 18 months

Question  What is the effect of a multicomponent workplace wellness program on health and economic outcomes?

Findings  In this cluster randomized trial involving 32 974 employees at a large US warehouse retail company, worksites with the wellness program had an 8.3-percentage point higher rate of employees who reported engaging in regular exercise and a 13.6-percentage point higher rate of employees who reported actively managing their weight, but there were no significant differences in other self-reported health and behaviors; clinical markers of health; health care spending or utilization; or absenteeism, tenure, or job performance after 18 months.

Meaning  Employees exposed to a workplace wellness program reported significantly greater rates of some positive health behaviors compared with those who were not exposed, but there were no significant effects on clinical measures of health, health care spending and utilization, or employment outcomes after 18 months

Abstract

Importance  Employers have increasingly invested in workplace wellness programs to improve employee health and decrease health care costs. However, there is little experimental evidence on the effects of these programs.

Objective  To evaluate a multicomponent workplace wellness program resembling programs offered by US employers.

Design, Setting, and Participants  This clustered randomized trial was implemented at 160 worksites from January 2015 through June 2016. Administrative claims and employment data were gathered continuously through June 30, 2016; data from surveys and biometrics were collected from July 1, 2016, through August 31, 2016.

Interventions  There were 20 randomly selected treatment worksites (4037 employees) and 140 randomly selected control worksites (28 937 employees, including 20 primary control worksites [4106 employees]). Control worksites received no wellness programming. The program comprised 8 modules focused on nutrition, physical activity, stress reduction, and related topics implemented by registered dietitians at the treatment worksites.

Main Outcomes and Measures  Four outcome domains were assessed. Self-reported health and behaviors via surveys (29 outcomes) and clinical measures of health via screenings (10 outcomes) were compared among 20 intervention and 20 primary control sites; health care spending and utilization (38 outcomes) and employment outcomes (3 outcomes) from administrative data were compared among 20 intervention and 140 control sites.

Results  Among 32 974 employees, the mean participation rate in surveys and screenings at intervention sites was 36.2% to 44.6% (n = 4037 employees) and at primary control sites was 34.4% to 43.0% (n = 4106 employees) (mean of 1.3 program modules completed). After 18 months, the rates for 2 self-reported outcomes were higher in the intervention group than in the control group: for engaging in regular exercise and for actively managing weight (69.2% vs 54.7%; adjusted difference, 13.6 percentage points; adjusted P = .02). The program had no significant effects on other prespecified outcomes: 27 self-reported health outcomes and behaviors (including self-reported health, sleep quality, and food choices), 10 clinical markers of health (including cholesterol, blood pressure, and body mass index), 38 medical and pharmaceutical spending and utilization measures, and 3 employment outcomes (absenteeism, job tenure, and job performance).

Conclusions and Relevance  Among employees of a large US warehouse retail company, a workplace wellness program resulted in significantly greater rates of some positive self-reported health behaviors among those exposed compared with employees who were not exposed, but there were no significant differences in clinical measures of health, health care spending and utilization, and employment outcomes after 18 months. Although limited by incomplete data on some outcomes, these findings may temper expectations about the financial return on investment that wellness programs can deliver in the short term.

The article is available in full from JAMA 

In the news:

The Independent Workplace wellness schemes don’t improve productivity or cut absences, trial finds

Statins likely to prevent cardiovascular events in Rheumatoid Arthritis patients

University of Manchester|  April 2019 | Statins likely to prevent cardiovascular events in Rheumatoid Arthritis patients

Researchers investigated the potential risks and benefits of statins in moderate risk patients with rheumatoid arthritis, designed the Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Patients with Rheumatoid Arthritis (TRACE RA), a multi-center, randomized, double-blind trial comparing the statin atorvastatin with placebo. 

The results of the trial show that patients with rheumatoid arthritis are likely to experience the same level of cardiovascular benefits as other patients.

Read the press release from the University of Manchester

The findings have been published in the journal Arthritis and Rheumatology

Abstract

Objective

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

Methods

Randomized, double‐blind, placebo‐controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

Results

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90‐3.49) [7,827 patient‐years] – early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo; adjusted hazard ratio. At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL‐cholesterol compared to placebo was also significantly lower on atorvastatin than placebo. CVE risk reduction per mmol/L LDLc reduction was 42%. Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

Conclusion

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists’ Collaboration meta‐analysis of statin effects in other populations.

This article is available to Rotherham NHS staff  and can be requested here 

University of Leeds research: Key step forward in tackling neurodegenerative diseases

University of Leeds | April 2019 | Key step forward in tackling neurodegenerative diseases

protein complex has been shown to play a key role in preventing the build-up of toxic plaques in the brain linked to neurodegenerative disorders such as Alzheimer’s and Huntington’s disease.

A research team including experts from the University of Leeds, Standford University and the University of Konstanz  have discovered that a protein helps to prevent the aggregation of damaging proteins within the cell.

This nascent polypeptide-associated complex (NAC) has been patented by the scientists, NAC, is a molecular chaperone found in all eukaryotic organisms, and is required for healthy cellular activity. NAC is known to help in the production of new proteins, and has now been shown to play an additional role in preventing cellular degeneration, by ‘catching out’ the proteins responsible for plaque formation.

This is a key step forward in tackling neurodegenerative diseases

Read the full news story from the University of Leeds 

Shen, Koning et al. | 2019| Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies |Molecular Cell | Published: April 11, 2019DOI:https://doi.org/10.1016/j.molcel.2019.03.012

Summary

The nascent polypeptide-associated complex (NAC) is a conserved ribosome-associated protein biogenesis factor. Whether NAC exerts chaperone activity and whether this function is restricted to de novo protein synthesis is unknown. Here, we demonstrate that NAC directly exerts chaperone activity toward structurally diverse model substrates including polyglutamine (PolyQ) proteins, firefly luciferase, and Aβ40. Strikingly, we identified the positively charged ribosome-binding domain in the N terminus of the βNAC subunit (N-βNAC) as a major chaperone entity of NAC. N-βNAC by itself suppressed aggregation of PolyQ-expanded proteins in vitro, and the positive charge of this domain was critical for this activity. Moreover, we found that NAC also exerts a ribosome-independent chaperone function in vivo. Consistently, we found that a substantial fraction of NAC is non-ribosomal bound in higher eukaryotes. In sum, NAC is a potent suppressor of aggregation and proteotoxicity of mutant PolyQ-expanded proteins associated with human diseases like Huntington’s disease and spinocerebellar ataxias.

The full research article is available in Molecular Cell, where it may be read in full.

 

 

 

Global, national, and urban burdens of paediatric asthma incidence attributable to ambient NO2 pollution: estimates from global datasets

Achakulwisut, P., Brauer, M., Hystad, P., Anenberg, S. | 2019 | The Lancet Planetary Health | DOI:https://doi.org/10.1016/S2542-5196(19)30046-4

Paediatric asthma is associated with exposure to traffic-related pollution (TRAP) but this burden remains poorly quantified. A global study (which used data from 194 countries) from George Washington University finds that around 13 per cent of new cases of asthma worldwide are caused by pollution.  Nitrogen dioxide (NO2) is a major component and common proxy of TRAP; this study estimated the annual global number of new paediatric asthma cases that could be attributed to NO2 exposure.  The research team recommend that the WHO’s guidelines for ambient  NO2 concentrations might need to be revisited as new diagnoses of paediatric asthma are in areas within WHO levels.

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Background

Paediatric asthma incidence is associated with exposure to traffic-related air pollution (TRAP), but the TRAP-attributable burden remains poorly quantified. Nitrogen dioxide (NO2) is a major component and common proxy of TRAP. In this study, we estimated the annual global number of new paediatric asthma cases attributable to NO2 exposure at a resolution sufficient to resolve intra-urban exposure gradients.

 

Methods

We obtained 2015 country-specific and age-group-specific asthma incidence rates from the Institute for Health Metrics and Evaluation for 194 countries and 2015 population counts at a spatial resolution of 250 × 250 m from the Global Human Settlement population grid. We used 2010–12 annual average surface NO2 concentrations derived from land-use regression at a resolution of 100 × 100 m, and we derived concentration-response functions from relative risk estimates reported in a multinational meta-analysis. We then estimated the NO2-attributable burden of asthma incidence in children aged 1–18 years in 194 countries and 125 major cities at a resolution of 250 × 250 m.

 

Findings

Globally, we estimated that 4·0 million (95% uncertainty interval [UI] 1·8–5·2) new paediatric asthma cases could be attributable to NO2pollution annually; 64% of these occur in urban centres. This burden accounts for 13% (6–16) of global incidence. Regionally, the greatest burdens of new asthma cases associated with NO2 exposure per 100 000 children were estimated for Andean Latin America (340 cases per year, 95% UI 150–440), high-income North America (310, 140–400), and high-income Asia Pacific (300, 140–370). Within cities, the greatest burdens of new asthma cases associated with NO2 exposure per 100 000 children were estimated for Lima, Peru (690 cases per year, 95% UI 330–870); Shanghai, China (650, 340–770); and Bogota, Colombia (580, 270–730). Among 125 major cities, the percentage of new asthma cases attributable to NO2 pollution ranged from 5·6% (95% UI 2·4–7·4) in Orlu, Nigeria, to 48% (25–57) in Shanghai, China. This contribution exceeded 20% of new asthma cases in 92 cities. We estimated that about 92% of paediatric asthma incidence attributable to NO2 exposure occurred in areas with annual average NO2 concentrations lower than the WHO guideline of 21 parts per billion.

Interpretation

Efforts to reduce NO2 exposure could help prevent a substantial portion of new paediatric asthma cases in both developed and developing countries, and especially in urban areas. Traffic emissions should be a target for exposure-mitigation strategies. The adequacy of the WHO guideline for ambient NO2 concentrations might need to be revisited.

Growth in e-cigarette use hasn’t led young people to think smoking is ‘normal’

University of Cardiff | April 2019 | Growth in e-cigarette use hasn’t led young people to think smoking is ‘normal’

During the four year period between 2011 and 2015 there was a reported increase in e-cigarettes during this time there was little regulation about their usage. 

Now analysis, which was led by Cardiff and conducted in collaboration with academics from Edinburgh, Stirling, Glasgow and Bristol, focused on three national surveys containing the views of 248,324 young people aged between 13 and 15. Participants were from Wales, England and Scotland.  

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The research shows the percentage of young people who reported that trying a cigarette was “OK” declined from 70% in 1999 to 27% in 2015, with the rate dropping faster from 2011 onwards. The percentage of young people reporting having tried smoking continued to decrease (Source: University of Cardiff).

Professor Linda Bauld from the University of Edinburgh added: “Teenagers across Great Britain were trying e-cigarettes during the period when they were unregulated, and recent data suggests that these trends have continued up to the present day. But the findings of this study show that youth tobacco smoking has nevertheless continued to decline. Clearly longer term data is required to fully assess the effects of e-cigarette use in young people. The next stages of this study and other ongoing research will provide us with more information in the future.”

University of Cardiff [press release] Growth in e-cigarette use hasn’t led young people to think smoking is ‘normal’

The research has been published in the journal Tobacco Control where it can be read in full here

A recent report from Public Health England on e-cigarette use finds that regular vaping remains low among young people, and has plateaued among adults.

Public Health England Regular e-cigarette use remains low among young people in Britain

PHE report on e-cigarette use finds that regular vaping remains low among young people, and has plateaued among adults.