Non-invasive smart capsule allows gut microbiome sampling

17th August 2020

Scientists at Purdue University, Indiana, have developed a new 3D-printed capsule that allows sampling of gut bacteria for further analysis and possible identification of disease.

Although a colonoscopy capsule camera has been available for some time to view areas of the intestines, current versions do not allow for sampling of the gut microbiome. The new battery-less capsule, which measures 9 mm by 15 mm has four components: a biodegradable cellulose acetate phthalate, pH-dependent, enteric coating, a 3D-printed housing, a sampling hydrogel and a gas permeable, flexible polydimethylsiloxane (PDMS) membrane.

The capsule is swallowed and upon reaching the small intestine, the enteric coating dissolves and entry of gut fluid which contains bacteria occurs via a small aperture. The intestinal fluid is then absorbed by the hydrogel which swells and in doing so, fills the volume of the capsule and pushes the PDMS membrane onto the sampling aperture, effectively sealing the device. The capsule is then retrieved from a faecal sample and a screw and thread on the capsule allows for it to be easily disassembled, the hydrogel removed and the bacteria present cultured and analysed. The capsule was thoroughly tested for leakage and its ability to absorb and maintain viable organisms in different extreme environments.

The capsule has been tested in pigs, who have a similar digestive tract to humans and the authors have filed a patent for the device.

Reference
Waimin JF et al. Smart capsule for non-invasive sampling and studying of the gastrointestinal microbiome. RSC Adv 2020;10:16313.

Rotigotine fails to improve cognitive functions in patients with Alzheimer’s disease

11th August 2020

Treatment with the dopamine agonist rotigotine does not lead to improvements in cognitive functions in those with mild to moderate Alzheimer’s disease, according to the results of a new randomised clinical study.

The Phase II double-blind trial, conducted by a team from the Department of Clinical and Behavioural Neurology, University of Rome, Italy, included 94 Alzheimer’s disease patients (mean age 73.9 years), of whom 58 were females and randomised them to transdermal rotigotine 4mg (starting at 2mg for 7 days) daily or matching placebo in addition to their stable drug regime.

The primary endpoint was the change after 24 weeks in the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog-11), which ranges from 0 (best) to 70 (worst) and measures the severity of impairment in 11 tasks covering including memory, language, and executive functioning. They also included a range of secondary outcome measures including Alzheimer Disease Cooperative Study–Activities of Daily Living score (ADCS-ADL) and Frontal Assessment Battery (FAB) score.

After 24 weeks of therapy, there was no significant change in the ADAS-Cog-11 mean score, 2.92 vs 2.66 (rotigotine vs placebo, p = 0.82). However, there were improvements in the ADCS-ADL and FAB scores among those using rotigotine and the authors suggested that the drug may have a potential effect in in delaying impairment of activities of daily living (ADCS-ADL) and reducing symptoms associated with frontal lobe cognitive dysfunction (that is, FAB score).

Reference
Koch G et al. Effect of rotigotine vs placebo on cognitive functions among patients With mild to moderate Alzheimer disease: A randomized clinical trial. JAMA Netw Open 2020;3(7):e2010372.

Cosentyx® receives EU approval as first-line system for paediatric psoriasis

Novartis has been granted EU approval for Cosentyx® (secukinumab) for the treatment of children aged 6 to < 18 years with moderate-to-severe plaque psoriasis.

The approval was based on two Phase III trials in children (within this age range) which found that two doses (75-150mg) and a higher dose (75-300mg) were effective at rapidly improving both skin symptoms and quality of life up to 52 weeks. The dosages are based on the weight of child and are 75mg for children up to 50kg and 150mg for those who are 50kg and over, although this dosage can be increased to 300mg if required.

The studies, which have yet to be published, found that the low dosage regime resulted in 93% of children achieving a psoriasis area severity index (PASI) 75 as early as 12 weeks. The PASI score is a measure of disease severity and a PASI 75 equates to a 75% reduction in disease severity from baseline. The study also found that 59.5% of children were completely clear of psoriasis (that is, achieved a PASI 100) after 12 weeks. In addition, the low dose ensured sustained skin clearance through to the study end (52 weeks) with 75% of children achieving a PASI 90 at this point.

Complete relief of symptom burden (that is, no impact on quality of life) was achieved by half of all children with moderate-to-severe psoriasis after 12 weeks and by 60.6% of children at the end of the study.

Cosentyx® appeared to be safe and there were no new safety signals generated by the study.

Reference
Novartis Media release. www.novartis.com/news/media-releases/novartis-cosentyx-receives-eu-approval-first-line-systemic-treatment-pediatric-psoriasis

Large-scale population testing needed to prevent a second COVID-19 wave

A modelling study has suggested that if the UK is to avoid a second COVID-19 wave, there should be large-scale and population-wide testing of symptomatic individuals and effective tracing of their contacts who, if diagnosed should isolate.

The study, by a team from the London School of Hygiene and Tropical Medicine, involved the development of a mathematic model which described an individual’s contact networks, stratified into household, school, workplace and community layers. The model looked at varies scenarios based on two schools reopening either full-time or on a part-time rota and the extent of contact tracing with varying levels of testing.

The results suggested that with increased testing of symptomatic people and effective contact tracing and isolation, it is unlikely that there would be a second wave. Without these measures, reopening of schools and gradual relaxing of the lockdown measures, would lead to a second wave which would peak in December 2020 or February 2021 if the schools adopted a part-time rota system. The model also predicted that varying the rate of infectivity of children from 100 to 50% of that of older adults, a comprehensive test-trace-isolate system would be required to avoid a second wave.

The authors noted that it is currently unclear whether the test-trace-isolate system will achieve sufficient coverage and suggest that their approach would be an alternative to intermittent lockdown measures such as school closures.

Reference
Panovska-Griffiths J et al. Determining the optimal strategy for reopening schools, the impact of test and trace interventions, and the risk of occurrence of a second COVID-19 epidemic wave in the UK: a modelling study. Lancet Child Adolesc Health 2020; 3 Aug. https://doi.org/10.1016/aS2352-4642(20)30250-9

Long-term vitamin D supplementation does not prevent depression

Although observational data have suggested an association between low levels of serum vitamin D and higher late-life depression, according to a new randomised trial, supplementing with vitamin D had no significant impact on the incidence and recurrence of depression.

The trial, by a team from the Department of Psychiatry, Harvard Medical School, Boston, recruited 18,353 adults (49.2% women) with a mean age of 67.5 years who had no evidence of depression at baseline and followed them for 5.3 years. They were randomised to either vitamin D3 (2000IU/day) and fish oils or placebo.

There were two primary endpoints: risk of depression (or clinically relevant depressive symptoms) and longitudinal mood scores which were ascertained using the PHQ-8 scores, which ranged from 0 (least symptoms) to 24 (most symptoms).

The results showed that after 5 years, there were 609 cases of depression (or clinically relevant depressive symptoms) in the vitamin D3 groups and 625 in the placebo group. The adjusted hazard ratio was 0.97 (95% CI 0.87-1.09, p = 0.62). In addition, there were no significant differences the PHQ-8 scores. The authors were unable to explain their finding and noted the divergence from the observations data, which suggested that as vitamin D levels increased, the risk of depression decreased.

Interestingly, the authors did not make any reference to the effect of fish oils, even though those assigned to vitamin D were also taking a fish oil supplement.

Reference
Okereke OI et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood score. JAMA 2020;324(5):471-80 doi:10.1001/jama.2020.10224

UK Government rolls out new rapid coronavirus tests

3rd August 2020

Two new tests for COVID-19 which can produce results in 90 minutes, avoiding the need for laboratory testing, are to be rolled-out across hospitals and care settings in the UK.

The first test, LamPore, has been developed by Oxford Nanopore technologies and is able to detect active COVID-19 infection in both swab and salvia samples and has been shown to have the same sensitivity as lab-based tests. The aim is for the test to be used in hospitals, care homes and other settings to increase testing capacity ahead of winter. The palm-sized device, which can process up to 2000 tests day, will, in the future, also be able to detect multiple respiratory viruses in a single sample.

The second test, DnaNudge’s RNA COVID-19 test, which was developed by a team from Imperial college, London, uses a cheek swab sample which is directly inserted into the device, is based on a polymerase chain reaction and delivers the result in just over an hour.

According to the government press release, 450,000 LamPore swab tests will be available across adult care settings and laboratories from week commencing 10 August, 2020. The DnaNudge test has already been trialled in eight London hospitals to analysis DNA in nose swabs and it is expected that 5000 devices will be used in the coming months.

Reference
Roll-out of 2 new rapid coronavirus tests ahead of winter.
www.gov.uk/government/news/roll-out-of-2-new-rapid-coronavirus-tests-ahead-of-winter

Critical care guidelines inconsistent with WHO recommendations

An analysis of clinical practice guidelines (CPG) for the management of critically ill patients with COVID-19 has found a low level of agreement with recommendations by the World Health Organization (WHO).

In a cross-sectional study, a team from the Department of Pharmacy, Leeds Teaching Hospital and colleagues from Malaysia, reviewed CPGs published as of 30 April 2020 and compared the recommendations contained in these guidelines with those issued from WHO.

The researchers derived 13 reference recommendations from the WHO guidance and checked the extent to which the CPGs were consistent with these recommendations. A literature search yielded a total of 8 CPGs from across the world though there was consistency with only 1 of the 13 WHO reference recommendations, which was for the prescribing of thromboprophylaxis where there were no contraindications. However, several CPGs partially met the recommendations. For example, WHO recommended a target oxygen saturation of >94%, whereas many CPGs though mentioning the need for oxygen therapy did not specify a target level. Furthermore, while WHO discouraged the use of systemic corticosteroids, many CPGs encouraged the use of dexamethasone, after data from the recent RECOVERY trial.

The authors concluded that these inconsistencies should be addressed as there are potentially important implications for critically ill patients. They also noted that the results from clinical studies specific for COVID-19 should only be included in CPGs where unambiguous.

Reference
Kow CS et al. Consistency of recommendations form clinical practice guidelines for the management of critically ill COVID-19 patients. Eur J Hosp Pharm 2020; 31 July 2020. doi: 10.1136/ejhpharm-2020-002388

Modelling study suggests breathing and coughing can release large amounts of COVID-19

In a new mathematical modelling study, researchers from the Swiss Centre for Occupational and Environmental Health suggest that spending time in a small room with a COVID-19 super spreader poses a risk of infection and that this risk is further heightened if they are coughing.

The researchers modelled the impact of viral transmission for super spreaders, which are defined as those who emit a large number of microdroplets (and thus high amounts of COVID-19) during both coughing and normal breathing. For super spreaders, while most of the viral particles are carried in airborne microdroplets which deposit rapidly, there was estimated to be an portion of smaller particles which can remain in the air for extended period of time and these particles were very effective at reaching the lungs. Hence, there is a greater risk of infection for a person spending an extended period of time in the same room as a super spreader, especially if the cough, even when observing appropriate social distancing in the room.

In contrast, the modelling estimated that for infected individuals who are not super spreaders, that is, those with a typical viral load, the risk of infection is low when they are breathing normally and maintaining social distancing. Fortunately, the modelling suggests there are a small number of super spreaders but because these individuals are impossible to identify, strict respiratory protection is recommended when spending time in a small room.

Reference
Riediker M, Tsai DH. Estimation of viral aerosol emissions from simulated individuals with asymptomatic to moderate coronavirus disease 2019. JAMA Netw Open 2020;3(7):e2013807. doi:10.1001/jamanetworkopen.2020.13807

Less than a third of current COVID-19 studies are of high quality

According to a new analysis, only 29.1% of current COVID-19 studies have sufficient methodological strength to produce high quality evidence.

The researchers from Stanford University, USA, examined the characteristics and expected strength of evidence of all currently registered studies on ClinicalTrials.gov, in terms of the 2011 Oxford Centre for Evidence-based Medicine (OCEBM) level of evidence framework.

A total of 1551 studies identified met the inclusion criteria; 59% of which were interventional trials (including 664 randomised trials) and 41% were observational studies. However, from the total, only 451 studies (29.1%) could potentially yield OCEBM level 2 evidence, which is the highest level of individual study evidence. For example, across the 664 randomised controlled trials (RCTs), blinding (required for a level 2 study) was reported in only 364 and only 74 RCTs were placebo-controlled. For the 640 observational studies, 81% were single-centred and only 87 (13.6%) were of sufficient quality to yield level 2 OCEBM evidence.

The authors expressed concern that given the huge number of studies being made available via preprint (that is, prior to peer-review), the rapid dissemination of low quality evidence may influence public opinion and clinical practice in ways that were potentially harmful, especially at a time when high quality knowledge is critically needed.

Reference
Pundi K et al. Characteristics and strength of evidence of COVID-19 studies registered on ClinicalTrials.gov. JAMA Int Med 2020; 27 Jul doi:10.1001/jamainternmed.2020.2904

Vitamin D and omega-3 fatty acids supplements ineffective for chronic knee pain

An analysis suggests that supplementing with either vitamin D or omega-3 fatty acids has no effect in the long-term on osteoarthritic knee pain.

A team from Harvard University analysed the results from a subgroup of patients in the VITAL study which was designed to examine the effect of both vitamin D and omega-3 fatty acid supplementation on the primary prevention of cancer. Patients were randomised to receive vitamin D3 (2000IU/day) or omega-3 fatty acids 1g/day or placebo and followed by 5.3 years. Within this group was a “knee pain cohort” of self-reported chronic knee pain at enrolment and who, based on screening questions, appeared to have osteoarthritis.

Patients completed a pain and stiffness tool designed to assess the impact on pain from daily activities such as walking, climbing stairs etc and the analysis comprised 674 patients taking vitamin D and 695 omega-3 fatty acids, with a mean age of 67 years in both arms.

The results showed that at the last appointment, the mean pain scores were not significantly different between the vitamin D and omega-3 fatty acid groups compared to their respective placebo groups. There was also no change in analgesic use between the two groups over the study period.

The authors concluded that neither intervention was of value in osteoarthritis.

Reference
Iversen MD, Katz JN, Costenbader KH. The effects of Vitamin D and Marine Omega-3 fatty acid supplementation on chronic knee pain in older US adults: results from a randomised trial. Arthritis Rheumatol 2020; https://doi.org/10.1002/art.41416