Tuesday 1 December 2015

We're moving!


We're moving!  Check out our new home http://gerimedjc.utorontoeit.com/.

You'll find our blog. how to #GeriMedJC infographic, and archived #GeriMedJC tweetchats.

Saturday 28 November 2015

Dextromethorphan-Quinidine: not quite ready for prime time

We only chose one article for this month's #GeriMedJC.  It was a randomized controlled trial of dextromethorphan-quinidine for agitation in Alzheimer disease:

Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. 2015 Sep 22-29;314(12):1242-54. 

There was pretty much consensus that dextromethorphan-quinidine is not quite ready for prime time in the management of agitation in Alzheimer disease.  Among some important concerns raised were:

  • trial was funded by pharma
  • last-observation carried forward is not a recommended method for imputing missing data in dementia trials
  • biases introduced by the choice of rescue medication, Lorazepam
  • agitation in this trial lumped together verbal aggression, physical aggression, and non-aggressive activity (pacing, restlessness)
  • mode of action
Thank you to all those who joined in the discussion:

If you missed out on the tweetchat, don't despair!  Download the transcript here.

See you on December 18, 2015 at 08:00 ET for the next #GeriMedJC!  Articles will be announced in advance by @GeriMedJC

Sunday 22 November 2015

Agitation. All behaviour has meaning.

Agitation.  All behaviour has meaning.  There is a never-ending search for some magical pill. But what must the experience be like for the person living with dementia?   This trial on Dextromethorphan-Quinidine for agitation in Alzheimer's disease doesn't necessarily answer this latter, probably more important question.  We will tackle this interesting trial at the next #GeriMedJC on November 27 at 08:00 ET / 13:00 GMT.


PMID: 26393847


Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia: A Randomized Clinical Trial. JAMA. 2015 Sep 22-29;314(12):1242-54. 

IMPORTANCE:
Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking.

OBJECTIVE:
To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation.

DESIGN, SETTING, AND PARTICIPANTS:
Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed.

INTERVENTIONS:
In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1:1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60).

MAIN OUTCOMES AND MEASURES:
The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]).

RESULTS:
A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo (ordinary least squares z statistic, -3.95; P < .001). In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. Between-group treatment differences were significant in stage 1 (least squares mean, -1.5; 95% CI, -2.3 to -0.7; P<.001). In stage 2, NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo. Between-group treatment differences were also significant in stage 2 (least squares mean, -1.6; 95% CI, -2.9 to -0.3; P=.02). Adverse events included falls (8.6% for dextromethorphan-quinidine vs 3.9% for placebo), diarrhea (5.9% vs 3.1% respectively), and urinary tract infection (5.3% vs 3.9% respectively). Serious adverse events occurred in 7.9% with dextromethorphan-quinidine vs 4.7% with placebo. Dextromethorphan-quinidine was not associated with cognitive impairment, sedation, or clinically significant QTc prolongation.

CONCLUSIONS AND RELEVANCE:
In this preliminary 10-week phase 2 randomized clinical trial of patients with probable Alzheimer disease, combination dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated.

Wednesday 11 November 2015

Are you a fan of Twitter journal clubs like us?

Are you a fan of Twitter journal clubs like us?

At the American College of Rheumatology 2015 Annual Meeting, #RheumJC shared their experience of running a Twitter journal club. The abstract is posted below and you can see a copy of their poster here.


#Rheumjc: Development, Implementation and Analysis of an International Twitter-Based Rheumatology Journal Club

Background/Purpose: Twitter is an increasingly popular platform for discussion and engagement amongst healthcare professionals. Here we describe the development, implementation and analysis of a rheumatology focused journal club on Twitter which utilizes the hashtag #RheumJC.

Methods: A #RheumJC development team was created, consisting of two academic rheumatologists, two private practice rheumatologists, and an adult/peds rheumatology Fellow in Training (FIT). A needs assessment survey was conducted to gauge interest and help define the structure of the proposed journal club, including preferred times and types of articles to be discussed. Prior to journal club sessions, requests were made for temporary open-access privileges to the article as well as invites to principal authors to participate. A total of 4 different journal clubs were conducted between January 29th and May 2nd, 2015, each consisting of two “live” one hour chats, occurring during the evening hours of GMT (European centric) and EST (Americas centric) respectively, as well as a full 24 hrs to allow for asynchronous participation. An analysis of the different sessions was performed to assess participant demographics and participation rates. A qualitative content analysis of the entire 96 hours of transcript (1927 tweets) was conducted with 6 coders assessing 363 tweets each (313 unique and 50 common). Inter-rater agreement was calculated using Krippendorff’s alpha. A second survey was conducted after the 4th journal club to assess participant satisfaction and identify additional strengths or barriers.

Results: In total, 133 individuals from 31 different countries participated in at least one #RheumJC session. While the majority of participants were rheumatologists, over 8 different medical fields were represented. There were 13 FIT and other trainees amongst the participants. 38 individuals participated in at least 2 different journal clubs, 16 participated in at least 3, and 8 individuals were present at all four. The mean number of tweets during each of the live journal clubs sessions (n=8) was 197 (166 unique tweets, 31 re-tweets). For 2 of the journal clubs, principal authors of the manuscript were able to participate. A qualitative content analysis (inter-rater agreement alpha =0.801) revealed that the majority of the conversation was relevant with 28% of the tweets addressing the article directly (in the spirit of a “traditional” journal club) and another 62% considered “on-topic” with tweets referencing personal experiences, opinions, and links to supporting literature. A survey conducted after the 4th journal club revealed that the majority (89%) of those who had participated were either satisfied or very satisfied with the #RheumJC initiative. Of interest, 11% of journal club participants indicated they had joined Twitter solely because of #RheumJC, and another 37% stated that #RheumJC had increased their use of Twitter as a tool for medical education.

Conclusion: #RheumJC is a novel and popular approach to the traditional medical journal club which brings together people from around the globe and across specialties to discuss current medical literature in rheumatology utilizing Twitter as a medium for medical education.


While you're at it, check out the cool poster from our #NephJC colleagues here and the abstract that presented at the 2015 American Society of Nephrology Kidney Week:


Participation in the Open, Online, Twitter-Based, Nephrology Journal Club, NephJC

Background: We established an online nephrology journal club, NephJC, in April 2014 that meets twice monthly to discuss emerging research and clinical practice guidelines. We invite content experts and manuscript authors to the discussion. The meeting occurs on the public forum Twitter, allowing any interested individual to join. The purpose of NephJC is to provide a recurring, academically-minded event on Twitter to help establish this communication channel as one for serious nephrology discourse. In addition, online journal clubs are becoming a critical route for post publication peer review. In order to assess the impact of NephJC we reviewed participation in the discussions over the first year.

Methods: We searched the Symplur analytics database for all tweets with the hashtag #NephJC from March 16, 2014 to June 2, 2015. We measured the numbers of participants, number of tweets and assessed participation over the first 27 NephJC sessions.

Results: From April 29th to June 2nd, 2015, 27 topics were discussed. 27 Chats were at 9PM Eastern for the Americas and starting Dec 18, 2014 a Europe and Africa chat was added at 8PM GMT. 10 GMT chats have been held, generally one day after the American chat. 1,022 Twitter accounts have used the hashtag #NephJC a total of 14,891 times. The median journal club chat has 41.5 (IQR 30.5-56.5) participants and 353.5 (IQR 268.5-633.5) tweets. The number of participants and tweets increased over time (P<0.01). The addition of the GMT chat was responsible for some of that growth (median number of tweets increased from 273 to 662.5, P<0.001, participants from 35 to 60.5, P<0.001).

Conclusions: NephJC has established itself as an integral part of the online digital mentorship curricula. The sustained usage and growth in participation of NephJC demonstrates the positive value of Twitter in medical education.

Make sure to engage in some other medical Twitter journal clubs out there: #RheumJC, #NephJC, #RespJC, etc.

Saturday 24 October 2015

#GeriMedJC at #ICRE2015

We presented our first year's experience of #GeriMedJC at the International Conference on Residency Education in Vancouver during the Using Innovative Technologies for Medical Education session.  View the slides below.

Thank you to all our tweeps for helping to grow this community!



Friday 23 October 2015

October 2015 #GeriMedJC

In an era of mounting evidence for comprehensive geriatric assessment in many settings (orthopedics, oncology), the question becomes whether this is not just clinically effective, but also cost-effective.  Another question remains as to how CGA be delivered -- in specialized geriatric wards or consultation models.  This randomized trial was chosen for this month's long discussion:

Comprehensive geriatric care for patients with hip fractures: a prospective, randomised, controlled trial. Lancet. 2015 Apr 25;385(9978):1623-33.

The choice of using the Short Performance Physical Battery as the main outcome measure was questioned.  It should be noted that the SPPB predicts other important outcomes.  It was reassuring to see that the primary and many of the secondary outcomes were favourable for geriatric care.

The short article generated a lot of interest! Ageism seen in the health care context may differ from attitudes about older people in general.  #GeriMedJC had a nice surprise today with first author, Rajvinder Samra, joining in for the tweet chat and fielding questions pertaining to the study:  

Medical students' and doctors' attitudes towards older patients and their care in hospital settings: a conceptualisation. Age Ageing. 2015 Sep;44(5):776-83. 

Our tweeps agreed with one of the study participants, that positive role-modelling and mentorship are important in formulating attitudes toward older patients. Our tweets identified specific mentors who influenced a career choice in geriatric medicine, check out some of the tweets here.

#GeriMedJC continues to grow, with a record of 264 tweets during this journal club session! 

Thanks to all those who participated:

Thanks once again to Dr. Bernadette Keefe (@nxtstop1) for Storifying this month’s tweet chat!!  If you missed the #GeriMedJC tweet chat, download the full transcript here.

We'll see you next time on #GeriMedJC on November 27 at 08:00 Eastern Time.

Was your choice to do geriatric medicine strongly influenced by a good mentor?

In today's #GeriMedJC discussion on this article by Samra et al. (Medical students' and doctors' attitudes towards older patients and their care in hospital settings: a conceptualisation. Age Ageing. 2015 Sep;44(5):776-83.), we posed this question to our tweeps: 

Was your choice to do geriatric medicine strongly influenced by a good mentor?

We received many responses, and yes, mentors are important!!



Friday 16 October 2015

Next #GeriMedJC on Oct 23 at 08:00 EDT

The October #GeriMedJC will take place on the 23rd at 08:00 Eastern / noon GMT.  We will tackle two interesting articles.  

Did you know that the live version of the Geriatric Medicine Journal Club held at the University of Toronto, is on the fourth Friday of the month from 08:00-09:00 ET? Postgraduate subspecialty trainees in Geriatric Medicine take turns leading the critical appraisal.  The first 45 minutes of the hour is devoted to the presentation and discussion of the long article and the latter 15 minutes is reserved for presentation and appraisal of the short article. The live version is also broadcast to several different hospitals in several different cities via the Ontario Telemedicine Network.

#GeriMedJC, the Twitter-complement to the traditional format journal club, has been up and running for over a year.  The intention is to engage an international dialogue across all time zones as a tweetchat should have no time restrictions.  


The first (long) article will look at hip fracture care models.  The link to the article can be accessed here.



Comprehensive geriatric care for patients with hip fractures: a prospective, randomised, controlled trial.Lancet. 2015 Apr 25;385(9978):1623-33.


BACKGROUND:

Most patients with hip fractures are characterised by older age (>70 years), frailty, and functional deterioration, and their long-term outcomes are poor with increased costs. We compared the effectiveness and cost-effectiveness of giving these patients comprehensive geriatric care in a dedicated geriatric ward versus the usual orthopaedic care.

METHODS:

We did a prospective, single-centre, randomised, parallel-group, controlled trial. Between April 18, 2008, and Dec 30, 2010, we randomly assigned home-dwelling patients with hip-fractures aged 70 years or older who were able to walk 10 m before their fracture, to either comprehensive geriatric care or orthopaedic care in the emergency department, to achieve the required sample of 400 patients. Randomisation was achieved via a web-based, computer-generated, block method with unknown block sizes. The primary outcome, analysed by intention to treat, was mobility measured with the Short Physical Performance Battery (SPPB) 4 months after surgery for the fracture. The type of treatment was not concealed from the patients or staff delivering the care, and assessors were only partly masked to the treatment during follow-up. This trial is registered with ClinicalTrials.gov, number NCT00667914.

FINDINGS:

We assessed 1077 patients for eligibility, and excluded 680, mainly for not meeting the inclusion criteria such as living in a nursing home or being aged less than 70 years. Of the remaining patients, we randomly assigned 198 to comprehensive geriatric care and 199 to orthopaedic care. At 4 months, 174 patients remained in the comprehensive geriatric care group and 170 in the orthopaedic care group; the main reason for dropout was death. Mean SPPB scores at 4 months were 5·12 (SE 0·20) for comprehensive geriatric care and 4·38 (SE 0·20) for orthopaedic care (between-group difference 0·74, 95% CI 0·18-1·30, p=0·010).

INTERPRETATION:

Immediate admission of patients aged 70 years or more with a hip fracture to comprehensive geriatric care in a dedicated ward improved mobility at 4 months, compared with the usual orthopaedic care. The results suggest that the treatment of older patients with hip fractures should be organised as orthogeriatric care.


For the second (short) article, we'll take a look at medical education. Great news!  The full text is available free here:


Medical students' and doctors' attitudes towards older patients and their care in hospital settings: a conceptualisation. Age Ageing. 2015 Sep;44(5):776-83. 


BACKGROUND:

despite assertions in reports from governmental and charitable bodies that negative staff attitudes towards older patients may contribute to inequitable healthcare provision for older patients when compared with younger patients (those aged under 65 years), the research literature does not describe these attitudes in any detail.

OBJECTIVE:

this study explored and conceptualised attitudes towards older patients using in-depth interviews.

METHODS:

twenty-five semi-structured interviews with medical students and hospital-based doctors in a UK acute teaching hospital were conducted. Participants were asked about their beliefs, emotions and behavioural tendencies towards older patients, in line with the psychological literature on the definition of attitudes (affective, cognitive and behavioural information). Data were analysed thematically.

RESULTS:

attitudes towards older patients and their care could be conceptualised under the headings: (i) beliefs about older patients; (ii) older patients' unique needs and the skills required to care for them and (iii) emotions and satisfaction with caring for older patients.

CONCLUSIONS:


our findings outlined common beliefs and stereotypes specific to older patients, as opposed to older people in general. Older patients had unique needs concerning their healthcare. Participants typically described negative emotions about caring for older patients, but the sources of dissatisfaction largely related to the organisational setting and system in which the care is delivered to these patients. This study marks one of the first in-depth attempts to explore attitudes towards older patients in UK hospital settings.


Saturday 26 September 2015

These tweeps love #GeriMedJC and we hope you do too!

It's been just over a year since we launched #GeriMedJC, the Twitter complement to the traditional format Geriatric Medicine journal club at the University of Toronto.  Reflecting on the experience, these are some tweets about #GeriMedJC that illustrate the interest:

What could be more fun than #GeriMedJC on a Friday morning?  We've had fun this year, and hopefully you have too!

As Geriatric Medicine trainees come and go, it's great to see they take #GeriMedJC with them to their new locations of practice.

We're thrilled to have social media in medicine gurus like Bernadette Keefe join in and retweet to her wider audience:

Even though the live version of #GeriMedJC is in Toronto, Canada, it's great to learn that our colleagues across the pond are at least lurking!

Even when #GeriMedJC fans are vacationing in Disney World, the most magical place on earth, there's time for #GeriMedJC.  Take that, Mickey Mouse!

And even after a year of participating in the live version of #GeriMedJC through the Ontario Telehealth Network, we're glad to hear participants seeing the added value of the Twitter complement.  We think it's a great medical education, advocacy and networking tool and hope you do too!

We look forward to another year of international engagement!  Thanks, tweeps!

A great turnout for Sep 2015 #GeriMedJC

The first half-hour of the live version of #GeriMedJC was facilitated by Amanda Gardhouse (@agardhouse), a Geriatric Medicine postgraduate trainee at the University of Toronto.  After conducting a focus group mid-way through out first year of #GeriMedJC, we learned that one of the barriers to faculty and trainee engagement on #GeriMedJC was due to a lack of familiarity with Twitter.  We gained 33 new followers since the last month, of which many were faculty in our division at the university.  Welcome tweeps!

During the second hour, this article was critically appraised:


Mossello E, Pieraccioli M, Nesti N, Bulgaresi M, Lorenzi C, Caleri V, Tonon E, Cavallini MC, Baroncini C, Di Bari M, Baldasseroni S, Cantini C, Biagini CA, Marchionni N, Ungar A.Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs. JAMA Intern Med. 2015 Apr;175(4):578-85. 

Overall, the audience thought the conclusions may have been a bit of a stretch and the follow-up was on the short side.  Nevertheless, caution should be raised in the setting of low blood pressure.  View the entire tweet chat transcript here.  Thank you to all the participants for making this one of the biggest #GeriMedJC sessions!



We're grateful to Dr. Bernadette Keefe (@nxtstop1), social media in medicine guru, from North Carolina who storified this discussion (click here)!

We'll see you next time on #GeriMedJC (October 30, 2015 at 08:00 ET / 12:00 GMT).

Thursday 17 September 2015

Something a bit different for the September 2015 #GeriMedJC

Did you know that the live version of the Geriatric Medicine Journal Club held at the University of Toronto, is on the last Friday of the month from 08:00-09:00 ET?  Postgraduate subspecialty trainees in Geriatric Medicine take turns leading the critical appraisal.  Article selection is guided by a clinician-scientist.  The first 45 minutes of the hour is devoted to the presentation and discussion of the long article and the latter 15 minutes is reserved for presentation and appraisal of the short article. The live version is also broadcast to several different hospitals in several different cities via the Ontario Telemedicine Network.

#GeriMedJC, the Twitter-complement to the traditional format journal club, has been up and running for over a year.  The intention is to engage an international dialogue across all time zones as a tweetchat should have no time restrictions.  

We obtained feedback about the first year's experience from our postgraduate trainees and faculty. One of the challenges was hesitancy to engage on the Twitter medium due to unfamiliarity with Twitter. However, there was recognition and appreciation for #GeriMedJC to engage international experts and dialogue. Therefore, in the September 2015 live version of #GeriMedJC, we will be devoting the first half of the hour on how to get started on using Twitter for journal clubs as well as tips for the advanced tweep.  In the meantime, check out our cool new infographic, How to #GeriMedJC. Another feedback suggestion was to have a repository of the previous articles and transcripts of the tweet chats much like the #RheumJC and #NephJC folks.  Look out for our new #GeriMedJC website which is under construction!  

Since the first half of the hour of this month's live #GeriMedJC will be devoted to How to #GeriMedJC, the critical appraisal of the short article will commence at 08:30 ET / 12:30 GMT. 

The association between blood pressure and cognitive function remains controversial with studies showing mixed results.  This may yet be another example of 'not one size fits all'. People are individuals, not numbers.



Mossello E, Pieraccioli M, Nesti N, Bulgaresi M, Lorenzi C, Caleri V, Tonon E, Cavallini MC, Baroncini C, Di Bari M, Baldasseroni S, Cantini C, Biagini CA, Marchionni N, Ungar A.Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs. JAMA Intern Med. 2015 Apr;175(4):578-85. 

PMID: 25730775

Access the article here or read the abstract below:

IMPORTANCE:
The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized.

OBJECTIVE:
To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI).

DESIGN, SETTING, AND PARTICIPANTS:
Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics.

MAIN OUTCOMES AND MEASURES:
Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up.

RESULTS:
We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤ 128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥ 145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change.

CONCLUSIONS AND RELEVANCE:
Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP lowering may be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help avoid high blood pressure overtreatment in this population.

Can't join us live? No worries!  Engage in the discussion on Twitter on August 28, 2015 at 08:00 ET / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.

Wednesday 16 September 2015

Want to #GeriMedJC, but don't know how? Check out our new infographic!


A special thanks to Thomas Galati, a Masters of Computer Science student at UOIT!

Study author joins us for a successful August 2015 #GeriMedJC

The two articles critically appraised and discussed during the August 2015 #GeriMedJC were:

Delayed-start analysis: Mild Alzheimer's disease patients in solanezumab trials, 3.5 years. Alzheimer's & Dementia: Translational Research & Clinical Interventions. In press. 2015. 

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96. 

It was a nice treat to have one of the study authors from the Zoster vaccine trial, Dr. Jan McElhaney, join us live via the Ontario Telemedicine Network and Twitter (@vitality_md) for commentary.

We continue to grow and now have close to 550 followers!

Missed the discussion?  You can get the transcript of the #GeriMedJC tweet chat here.

Thanks again to all those who participated in the Tweet chat:

You may also view articles discussed at prior #GeriMedJC tweetchats at PubMed Commons. (link) The next #GeriMedJC will be on September 25, 2015 at 08:00 ET / noon GMT. Stay tuned for the articles!

Monday 24 August 2015

August 2015 #GeriMedJC articles

This month we will be discussing two articles. In the live version of the Geriatric Medicine Journal Club held at the University of Toronto, the first 45 minutes of the hour is devoted to the presentation and discussion of the long article and the latter 15 minutes is reserved for presentation and appraisal of the short article.

Did you know that the live version of #GeriMedJC runs for an hour and is broadcast to several different hospitals in four different cities via the Ontario Telemedicine Network? 

Toronto: Mount Sinai Hospital, Sunnybrook Hospital, St. Michael’s Hospital, Baycrest Hospital, North York General Hospital, St. Joseph’s Hospital
Mississauga: Trillium Hospital
Kitchener-Waterloo: Grand River Hospital, St. Mary's Hospital
Orillia: Soldier's Memorial Hospital

Can't join us live? No worries!  Engage in the discussion on Twitter on August 28, 2015 at 08:00 EDT / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.


The long article this month should provide an interesting discussion on study design and statistical methodology.  This study utilizes a delayed-start, also known as randomized-start, to demonstrate disease-modification drug effect.  We will take a look at this study of an investigational treatment for mild Alzheimer's disease:


Delayed-start analysis: Mild Alzheimer's disease patients in solanezumab trials, 3.5 years. Alzheimer's & Dementia: Translational Research & Clinical Interventions. In press. 2015. 

Access the article here or read the abstract below:

Introduction
Solanezumab is an anti-amyloid monoclonal antibody in clinical testing for treatment of Alzheimer's disease (AD). Its mechanism suggests the possibility of slowing the progression of AD.

Methods
A possible disease-modifying effect of solanezumab was assessed using a new statistical method including noninferiority testing. Performance differences were compared during the placebo-controlled period with performance differences after the placebo patients crossed over to solanezumab in the delayed-start period.

Results
Noninferiority of the 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) and Alzheimer's Disease Cooperative Study Activities of Daily Living inventory instrumental items (ADCS-iADL) differences was met through 132 weeks, indicating that treatment differences observed in the placebo-controlled period remained, within a predefined margin, after the placebo group initiated solanezumab. Solanezumab was well tolerated, and no new safety concerns were identified.

Discussion

The results of this secondary analysis show that the mild subgroup of solanezumab-treated patients who initiated treatment early, at the start of the placebo-controlled period, retained an advantage at most time points in the delayed-start period.



The short article discussion will follow the long article discussion.  The currently available live-attenuated vaccine against herpes zoster has two major limitations: diminishing efficacy against shingles with increasing age of vaccine recipients and contraindication for use in immunocompromised individuals.  Could recombinant subunit vaccines fill in this gap?  In this month's #GeriMedJC, the following trial will be appraised.


Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96. 

PMID: 25916341

Access the article here or read the abstract below:

BACKGROUND:
In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.

METHODS:
We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.

RESULTS:
A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.

CONCLUSIONS:
The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups.

Saturday 25 July 2015

Short article for July's #GeriMedJC

After a short hiatus in June, #GeriMedJC returns on July 31, 2015 at 08:00 EDT / noon GMT.

See the previous blog post for the long article which will precede the short article discussion.
What does a short article mean?  In the live version of the Geriatric Medicine Journal Club held at the University of Toronto, the last 15 minutes of the hour is devoted to the presentation and discussion of the article. The study chosen for the short article discussion is:


Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63.

PMID: 25771249

Access the article here or read the abstract below:

BACKGROUND:
Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.

METHODS:
In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989.

FINDINGS:
Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control).

INTERPRETATION:

Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.

Did you know that the live version of #GeriMedJC runs for an hour and is broadcast to several different hospitals in four different cities via the Ontario Telemedicine Network? 

Toronto: Mount Sinai Hospital, Sunnybrook Hospital, St. Michael’s Hospital, Baycrest Hospital, North York General Hospital, St. Joseph’s Hospital
Mississauga: Trillium Hospital
Kitchener-Waterloo: Grand River Hospital, St. Mary's Hospital
Orillia: Soldier's Memorial Hospital

Can't join us live? No worries!  Engage in the discussion on Twitter on July 31, 2015 at 08:00 EDT / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.

Sunday 19 July 2015

#GeriMedJC is back for July!

After a short hiatus in June, #GeriMedJC returns on July 31, 2015 at 08:00 EDT / noon GMT.

What does a long article mean?  In the live version of the Geriatric Medicine Journal Club held at the University of Toronto, the first 45 minutes of the hour is devoted to the presentation and discussion of the article. The study chosen for the long article discussion is:



Kutner JS, Blatchford PJ, Taylor DH Jr, Ritchie CS, Bull JH, Fairclough DL, Hanson LC, LeBlanc TW, Samsa GP, Wolf S, Aziz NM, Currow DC, Ferrell B, Wagner-Johnston N, Zafar SY, Cleary JF, Dev S, Goode PS15, Kamal AH, Kassner C, Kvale EA, McCallum JG17, Ogunseitan AB, Pantilat SZ, Portenoy RK, Prince-Paul M, Sloan JA, Swetz KM23, Von Gunten CF, Abernethy AP. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015 May;175(5):691-700. 

This article is a great example of a trial which will inform evidence-based de-prescribing, a much needed area in an era of increasing numbers of clinical practice guidelines which concentrate usually on the opposite. 

Given the nature of the topic, we would like to extend a formal invitation to #hpm to weigh in on the discussion!
  
This article here and the abstract can be found below:

IMPORTANCE:
For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy.

OBJECTIVE:
To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting.

DESIGN, SETTING, AND PARTICIPANTS:
This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach.

INTERVENTIONS:
Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins.

MAIN OUTCOMES AND MEASURES:
Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings.

RESULTS:
A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P=.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P=.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were $3.37 per day and $716 per patient.

CONCLUSIONS AND RELEVANCE:
This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted.

Did you know that the live version of #GeriMedJC runs for an hour and is broadcast to several different hospitals in four different cities via the Ontario Telemedicine Network? 

Toronto: Mount Sinai Hospital, Sunnybrook Hospital, St. Michael’s Hospital, Baycrest Hospital, North York General Hospital, St. Joseph’s Hospital
Mississauga: Trillium Hospital
Kitchener-Waterloo: Grand River Hospital, St. Mary's Hospital
Orillia: Soldier's Memorial Hospital

Can't join us live? No worries!  Engage in the discussion on Twitter on July 31, 2015 at 08:00 EDT / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.