Background
Brian Rifkin
Potassium Rollercoaster Heartbreak

This week, we will discuss the use of 3K dialysis bath with sodium zirconium cyclosilicate versus 2K bath and no potassium lowering medications in dialysis patients and the associated risk of arrhythmia.

Potassium Rollercoaster Heartbreak
Background
Jade Teakell
FLOZINATing to the Future- Long Term Effects of ...

This week, we will discuss post-trial follow-up for EMPA-Kidney. What are the longer-term effects of empagliflozin for patients with chronic kidney disease?

FLOZINATing to the Future- Long Term Effects of Empagliflozin in Patients with CKD
Background
Brian Rifkin
The Ondansetron Ballet: Torsades de Pointes

Nausea is a very common and distressing problem. Some medications that treat nausea carry a higher risk for arrhythmias, like Torsades de Pointes, and sudden cardiac death. Is ondansetron safe for use in patients on hemodialysis?

The Ondansetron Ballet: Torsades de Pointes
Background
Cristina Adriana Popa
Re”FINE”ing the role of non steroidal MRAs in ...

This week, we will discuss non-steroidal mineralocorticoid antagonist in the multiverse of cardiovascular-kidney-metabolic. What FINEHEART pooled analysis would add to what we already learned from FIDELIO-DKD trial?

Re”FINE”ing the role of non steroidal MRAs in Cardio Kidney Metabolic syndrome
Background
Cristina Adriana Popa
Playing It Safe: Can Felzartamab Fill the Gap ...

This week is time antibody mediated rejection treatment in kidney transplant. A new molecule targeting CD38, on the horizon, safely tested in a phase 2 trial

Playing It Safe: Can Felzartamab Fill the Gap in AMR Treatment?

The Benefits of Nephro-Twitter. Or how I learned to stop fearing and love Twitter

Last week this tweet came across my feed and was widely and justifiably retweeted:

It became clear to me, that nephrology needed a similar essay:

Dr. Katie Kwon answered my call. Her essay:

My first foray into Twitter was about five years ago. Twitter was in the news a lot and I kept coming across online articles filled with viral tweets that were funny, pithy, and current. Those articles made Twitter seem like a virtual Algonquin Round Table. However, my first login didn’t look anything like that. Twitter asked for my email address book, then signed me up to follow people I already knew. I didn’t have the first idea how to go about seeing tweets from strangers on topics I found interesting. It was all too much work, and I quickly gave it up.

Then I attended ASN 2013. Since starting my nephrology training, I’ve tried to go every other year. I’m in private practice with two other colleagues, so ASN is my biannual chance to chat with other nephrologists. Slowly, painfully, I’ve grown my professional network. At first I would meet up with other alumni from my fellowship program and the faculty. Then, when our dialysis units were acquired by a small chain, I got to meet some other medical directors from around the country. It was nice to attend meetings knowing more than three people. But I knew I’d get a lot more out of ASN if I knew more people, and could learn their viewpoints on the presentations I was attending.

At the 2013 meeting, I had the opportunity to meet Joel Topf. He’s a nephrologist that I had long admired for his blog, and I had made comments on several of his posts that I particularly liked.  He sent me a message that he was presenting a poster at ASN, so I decided to stop by. His poster was about the use of social media in nephrology, an area where’s he’s an influential evangelist. After our conversation, I signed up for a new Twitter account.

This time, the experience made a little more sense. I learned that one’s Twitter feed is determined by who you follow. I started by following Joel and then anyone else he tweeted at. Pretty soon I had a nice stream of commentary from nephrologists from many different countries, most of it focused on the ongoing meeting. I began to notice the hashtags and how you could also search for those to pick up the threads of a conversation about a particular topic.

Using my iPhone, I carefully pecked out a few tweets about the presentations I attended. I tried to tweet pearls that normally I would have written down in a notebook, rarely to be seen again. I was delighted when these tweets got starred and retweeted by new followers. It was even more exciting when respected faculty members, whose names I knew from journal articles, would add their thoughts and provide links to additional material. It enhanced the learning from each session I attended. I wound up with a deeper understanding and different perspectives. I even made a few real-life acquaintances and met some for lunch. It was the most productive ASN meeting I’d ever attended.

Returning home, my Twitter use became much more sporadic. I had set up the app to send me a notification if a lot of the people I followed tweeted about a particular topic. In this way I learned about some breaking trials and other events in the broader field of medicine, including the MOC debate. I rarely tweeted my own content, but Twitter is very forgiving of long periods of inactivity. You won’t lose followers as you might if you took a break from blogging. When I did have something to contribute, or a question to ask, it was easy to jump right back in. I discussed a few tough cases on the Nephrology On Demand forum, which I learned about from Twitter.

I returned to ASN for the 2015 meeting. This time I was able to start tweeting  right away – thankfully, my phone remembered my Twitter password. I started by reading the comments from other people attending the plenary session. Their annotations and insights deepened my understanding of a topic that would otherwise be intimidatingly basic science in its orientation. I followed many more conference attendees who seemed to have valuable things to say. Then I realized that I could virtually attend multiple simultaneous sessions. This was great! I no longer had to miss talks that seemed interesting but conflicted with others I also wanted to see. I learned about great presentations on exciting topics as they unfolded in real time, and sometimes switched rooms midway through a session. The conference felt more dynamic and I was confident I was spending my time there wisely.

One session on Friday focused on the ongoing battle over MOC and the ABIM. This was a topic I had continued to follow for the past few years, and I was disappointed that it was so sparsely attended. However, the low turnout wound up having an unexpected benefit, which was a clear field for me to tweet about it. I tried to sum up each main point the speakers made, then highlight the comments from the audience. This was the first time my tweets seemed to resonate. My followers retweeted my reporting to their followers, and my audience grew. The instantaneous feedback that what I was doing had interest and value was fun and exciting.

I left ASN this year having met interesting colleagues across the country, both virtually and in real life. (Twitter is a great way to get people to visit your poster at ASN.) I picked up some tips to organize my feed, which made it easier to participate in the Nephrology Journal Club the next week. The discussion was about the SPRINT hypertension trial. It felt like being back in fellowship again, in a good way. I got to benefit from the analysis of hundreds of colleagues, both those who participated and through the links to commentary that they provided. I am in the process currently of writing a talk for our local primary care doctors about SPRINT, and the Twitter conversations I participated in are providing great material for my analysis.

Twitter has allowed me to connect with many more nephrologists than I would have managed to meet through more conventional means. Those relationships have real value, helping me stay current in my field and giving me varying perspectives on controversial topics.  While I love my practice in a small Midwestern town, Twitter has provided the discussions that I enjoyed during my training years in a big academic center. I feel more connected to my profession and my practice of medicine will only continue to improve as a result of my participation.

Quick start to Twitter as a nephrologist:

  1. Sign up. Keep your Twitter name short; 140 characters goes quick and a long name uses up more of them.
  2. Follow Nephrology Journal Club (@NephJC) and note the time of the upcoming discussion.
  3. Use tchat.io in your browser to follow the #NephJC discussion. Follow anyone who tweets something interesting. When you follow someone all of their Tweets show up in your feed. hand picking your feed will make Twitter more useful.
  4. Unfollowing is easy and it’s not fraught with emotion, unlike defriending on Facebook. Sometimes you’ll follow someone, only to find that the majority of their tweets are in a different language that you don’t understand. Unfollow them! If your feed is cluttered with irrelevant tweets, Twitter gets to be a slog.
  5. If someone is writing about an interesting topic marked with a #hashtag, just click on the hashtag to see other tweets with that hashtag. You can pick up more interesting people to follow.
  6. Start to tweet. Retweets are easy; bonus for adding your own viewpoint. Tweet about meetings or lectures you attend. You’ll get more out of it than jotting down notes you won’t read again. People will ask you questions or offer more resources. Your learning just doubled!
  7. It’s the internet; some people are weird, rude or hostile. Twitter has a block feature that prevents a person from reading your tweets or communicating with you. I don’t hesitate to block anyone who bothers me. I don’t want to use up any emotional energy worrying about a fleeting online interaction.
  8. Nephro-Twitter is a friendly place. If you start a message with someone’s username (i.e, @KatieKwonMD) your tweet will go directly to their feed, but not to your other followers.  If you include their username in the body of your tweet, all your followers can see it. Reach out to people, ask them questions, point them to links you think might interest them. That’s how interesting conversations start.

Kidney Week Wrap-up: How will we remember #KidneyWk 2015?

Kidney Week 2015 may be remembered for a number of different social media moments. The Tweet-Up was a raging success and finally broke through to become what Matt and I envisioned at the Denver Kidney Week in 2015. The success of the tweet-up was largely driven by Satellite Healthcare and their invaluable assistance with promotion and logistics. We can’t thank them enough. Additionally Kidney Week 2015 was marked by both a NephJC and NephMadness poster presentation. This Kidney Week, Matt was invited to give a talk on electronic medical education and he crushed it. But the biggest event, the one I hope we remember 2015 for, was the graduation of the first class of interns from the Nephrology Social Media Collective (NSMC).

Matt, Scherly and Chi with their diplomas and #DreamRCT mugs

Matt, Scherly and Chi with their diplomas and #DreamRCT mugs

We had four very different interns and they each had individually unique experiences with the internship:

Scherly Leon is in her last year of nephrology fellowship and is on a mission. She was already the ASN Public Policy Fellow when she started the Social Media internship. She is tuning her Twitter feed to be a carefully crafted curation of nephrology and social justice content. If you aren’t following Scherly (https://twitter.com/SLeonMD), you are doing it wrong. I think everyone is excited to see what she does with her growing skills as a public physician.

Chi Chu was the only intern who was not a nephrologist and we needed to apply more thought on how to make his experience particularly relevant for him. Chi participated in all of the events and his Which nephrotoxic antibiotic are you? was epic. Likewise his DreamRCT entry was equal parts creative and audacious. He will make an awesome nephrologist someday...if we are lucky enough to get him.

Hector Madariaga was a natural for the NSMC internship and did great work from day one. However, by June it was clear that we were under-utilizing him. So we brought him into NephJC in a more formal way. For the last six-months Hector has been NephJC’s chief archivist. He is in charge of creating the Storify’s from every chat. We hope he will continue to be a key member of the NephJC team. Future editor-in-chief?

Nikhil Shah is the intern who least needed the NSMC internship. He was doing great work before the internship and we just hitched our wagon to his shooting star. His SocialKidney project is an essential tool for tracking social media conversations online. His inspirational story on how he got hooked on nephrology was picked up by MedPage today.  It will be great to have his creativity on the NSMC team in the future.

There were several more interns in the inaugural class:

The fifth student was us. We learned a lot about what does and does not work in a social media internship. We are going to be better next year. We got lucky by requiring participation in NephJC, that turned out to be an exceptional learning tool. But only because the interns didn’t merely tune in and lurk, but actively participated and engaged in the chats. It was a great (if not accidental) flipped classroom experience.

With the graduation of our inaugural class we are excited to open the application period for the second class of NSMC interns. If you are interested or have questions, feel free to send us an e-mail. If you want to apply for a spot drop us an e-mail and explain:

  • Who you are 
  • Why you want to do the social media internship
  • What experience do you already have with social media (Do not be embarrassed to say none. Do not be embarrassed to say you are really good at Facebook quizes)

The due date for the application is January 24. We will make our decisions and start the program on February 1

 Send applications to NephrologyJC@gmail.com


Spironolactone primer

Resistant hypertension is an important clinical problem. It is commonly defined as inadequate blood pressure control despite use of three antihypertensive agents of different classes at optimal dosages; one of the three should be an appropriately dosed diuretic. About 10-15% of hypertensive patients have resistant hypertension.

The magical powers of aldosterone antagonists first started to be publicized in the late 90's and in 2003 Calhoun showed a dramatic effect among patients with resistant hypertension:

“A total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 ± 21 over 10 ± 14 mm Hg at 6 weeks and 25 ± 20 over 12 ± 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics.”

This was backed up by additional observational data as part of the ASCOT trial experience. The investigators found dramatic efficacy from modest doses of spironolactone among the 1,411 patients that received spironolactone as a fourth line agent:

“During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. ”

The first randomized, placebo controlled trial in resistant hypertension was published in 2011. The ASPIRANT trial (PDF) showed a more modest, but still clinically significant reduction blood pressure.

An important caution when looking at spironolactone data is that it appears that black patients  are more sensitive to increases in aldosterone, so one could predict more modest blood pressure improvements with spironolactone in a European population. See Tu et al. (Full text).

Another critical aspect of resistant hypertension is addressing non-adherence. 

“A mass spectrometry urine toxicology screening of antihypertensive drugs reported that 53% of patients with resistant hypertension were non-adherent to treatment. Of these, 70% were incompletely adherent and 30% were completely non-adherent. Reduced adherence was not attributed to a particular antihypertensive class. Another urine analysis study found that 23% of patients referred for renal denervation were completely non- adherent to their prescribed antihypertensive treatment.”
— From Rossignol et al. The double challenge of resistant hypertension and chronic kidney disease.

This is why PATHWAY-2's attempt to measure minimize non-adherence is so important.

This week's chat on PATHWAY-2 represents the first randomized controlled trial against an active control group. The fact that aldosterone rises above other fourth line agents to provide meaningful advantages in the treatment of resistant hypertension is important.

We are coming to a new age in hypertension management. On November 9, at 2:00 PM at the AHA meeting in Orlando the SPRINT Trial results will be released. This will almost certainly result in a wave of more aggressive blood pressure control. Almost simultaneously we now have access to the first of the next generation potassium binders, patiromer. This brings the hope of avoiding the most frightening of the side effects from aldosterone antagonists, hyperkalemia. These three seemingly unrelated events are going to be major influences on the treatment of hypertension going forward.

AskASN chat tonight about organ allocation

Tonight the AskASN chat will include Michelle Josephson, director of kidney transplantation at the University of Chicago and Nicolae Leca, medical director of Kidney and Pancreas Transplantation at the University of Washington.

The old system's framework wwas established in 1988 and was built in a world with a smaller transplant system.

Waiting time was the focus of the old system and did not match organs to patients by considering the duration the kidney would be needed which results in wasted kidney years. 

The goals of the new system include:

 

  • increase the life-years gained by kidney transplantation
  • maintain access to transplantation across all age groups
  • maintain priority for pediatric patients
  • improve access for sensitized recipients and minorities
  • promote use and recovery of expanded criteria kidneys by expanding the geographic sharing of these organs

This chat will discuss:

Why did the system change?

How has the transition gone so far?

What unexpected events have occurred?

Have you seen any changes?

How has the KDPI worked out?

Any changes or tweaks in the future?

Please join us right now!

The IV versus PO iron conundrum for Tuesday and Wednesday

Joel said he would write the summary. Suzanne said she would write the summary and in the end wires got crossed and they both wrote the summary. Sigh. We are ardent conservationists and strongly believe that no part of the buffalo should go to waste so here is Dr. Norby's summary of this week's NephJC article:

A randomized trial of intravenous and oral iron in chronic kidney disease

Rajiv Agarwal, John W Kusek, and Maria K Pappas

Kidney International advance online publication 17 June 2015

doi: 10.1038/ki.2015.163

BACKGROUND

Anemia is common in patient with stages 3-5 chronic kidney disease (CKD) due to decreased erythropoietin production as well as iron deficiency, including the functional iron deficiency that can develop while using erythropoiesis-stimulating agents (ESA).

The KDIGO Clinical Practice Guideline for Anemia in CKD recommends (grade 2C) the use of IV iron in adult patients with CKD note yet on dialysis if 1) an increase in hemoglobin level is desired to avoid or minimize blood transfusions and ESA use and/or to alleviate symptoms potentially related to anemia and 2) TSAT is ≤30% and ferritin is ≤500 ng/ml. The Guideline also states that a 1-3 month trial of oral iron may be considered for patients not yet on dialysis.

Safety and risks of IV iron use in the non-dialysis CKD population are not fully understood although an author of the current study, Agarwal, along with other colleagues previously demonstrated that IV iron use can lead to increased oxidative stress, endothelial damage, and even renal injury.

The hypothesis of the current study, REVOKE (randomized trial to evaluate intravenous and oral iron in chronic kidney disease), was that IV iron would result in greater decrease in kidney function compared with oral iron in iron-deficient patients with moderate to severe CKD not yet on dialysis.

METHODS

Design: open-label, parallel-group, active-control, single-center randomized trial

Setting: A safety-net hospital and a VA Hospital, both in Indianapolis, IN; August 2008 – November 2014.

Inclusion criteria:

  • ≥18 years old
  • eGFR 21-60 ml/min/1.73 m2, not on dialysis
  • Hemoglobin <12 g/dl
  • Serum ferritin <100 ng/ml or serum transferring saturation <25%

Exclusion criteria:

  • Pregnant or breast feeding females
  • Known hypersensitivity to any intravenous iron, iothalamate meglumine (Conray 60, Malinckrodt) or iodine
  • Severe anemia that required imminent red blood cell (RBC) transfusion (Hgb <8 g/dL) or the potential need for imminent RBC transfusion (e.g., active bleeding) 
  • Persons with acute kidney injury
  • History of intravenous iron use within the month prior to screening
  • Iron overload (serum ferritin >800 ng/nl or transferrin saturation >50%)
  • Anemia not caused by iron deficiency (e.g., sickle cell anemia)
  • History of surgery or systemic or urinary tract infection within the past month
  • Organ transplant recipients
  • Persons currently being treated with immunosuppressive agents

Randomization and Blinding: 1:1 ratio, using computer generated permuted blocks, randomized to either oral iron or IV iron using concealed opaque envelopes

Primary outcome: 

  • Difference between treatment groups in slope of mGFR decline from baseline to 2 years adjusted for the log of baseline urinary protein/creatinine ratio compared with baseline at 8 weeks, 6 months, 12 months, and 24 months after randomization.  

Secondary outcomes:

  • further adjustment of the primary outcome for age, sex, race (Black vs. non-Black), angiotensin-converting enzyme/angiotensin receptor blocker use, and the presence or absence of cardiovascular disease (all determined at baseline)
  • between-group % change in proteinuria from baseline to 8 weeks
  • difference between hemoglobin response between treatment groups
  • change in KDQOL

Statistical analysis:

  • Intention-to-treat, if the participant received at least one dose of study medication
  • Linear mixed model with GFR as outcome variable
  • Assumptions: mean rate of decline in GFR of 4 ml/min per 1.73 m2 per year in the oral iron group and a 50% greater decline in the IV iron group and a cumulative rate of dropout of 25%
  • Recruitment target of 100 patients for each treatment group with a minimum duration of follow-up of 2 years to achieve 82% power to detect hypothesized difference in decline in kidney function at the 5% level of significance
  • 2-sided t-test considered significant for p<0.05

INTERVENTION

Participants were treated over 8 weeks beginning at the time of randomization. Those randomized to the IV iron group received iron sucrose 200 mg IV over 2 h at weeks 0, 2, 4, 6, and 8. Participants randomized to oral iron were counseled to take ferrous sulfate 325 mg three times daily for 8 weeks.

RESULTS

Trial was terminated early due to higher serious adverse event rate in IV iron group (199 per 100 patient years) compared with oral iron group (168.4 per 100 patient years); adjusted incidence rate ratio 1.60 (1.28–2.00), P<0.0001.  Statistically significant increases in infections and cardiovascular events were observed. In particular, the incidence of lung and skin infections was increased 3-4x and of hospitalization for heart failure was increased 2x in the IV iron group after adjusting for the more favorable baseline characteristics in that group.

Decrease in mGFR between groups was similar between both groups, -3.6 ml/min per 1.73 m2 per year for oral iron group and -4 ml/min per 1.73 m2 per year for IV iron group. 

Hemoglobin increase, change in proteinuria over time, ESA use, and need for blood transfusions were not significantly different in the 2 groups. KDQOL domain scores did not change over time in either group.

DISCUSSION

Since this study was limited to patients with stage 3-4 CKD not yet on dialysis, results cannot be generalized to patients already on dialysis. 

The primary outcome of comparing decline in mGFR between groups could not be evaluated due to early termination of the study due to safety concerns related to increased risk of infection and cardiovascular events.  While additional studies evaluating the long-term safety of IV iron use in this population are necessary, should the oral route be preferred when initiating iron supplementation in patients with stage 3-4 CKD?  Moreover, based on the time course of hemoglobin increase in patients in the oral iron group of this study, it would seem reasonable that a trial of oral iron be given to patients with CKD not yet on dialysis for a full 3 months, rather than at least 1 month and up to 3 months as suggested in the KDOQI guidelines.

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The #nephJC #RIPC stats and @storify

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Both the chats were quite stimulating, we saw quite a number of new voices (whom we hope to see again!)

Hector did a great job, again, of storify-ing. Thanks again to Preeti Malani, Ed Livingston and the rest of the JAMA staff for their support. Look forward to the #JAMbag next time!


The winners of the #JAMAcup

At every #NephJC chat I find myself delighted with the bits of Twitter wisdom that get funneled through the hashtag. We are going to try to do a better job of rewarding the best of these. Some of these awards will even have prizes. This week we are delighted to announce winners of a great looking JAMA coffee mug, named the JAMAcup in this pre-chat banter:

The winner of the #JAMAcup for the Tuesday night chat is Azra Bihorac (@AzraBihorac) who wrote this gem: 

We would also like to give honorable mention (but no mug) to Mike Walsh (@lastwalsh) who was the first to alert us to the negative results for RIPC in other large trials:

The Wednesday chat was great and picking a winner was difficult but we selected this dejavu all over again tweet by Graham Abra (@GrahamAbra):

Honorable mention to Michael Hultström (@mhulstrom) for this:

 

A hearty thanks to JAMA. We love working with them and appreciate their support of post-publication peer review.

#NephJC does #RIPC Tues Aug 11 and Wed Aug 12. And thanks to @jama_current

RIPC = Remote Ischemic PreConditioning

We hope to see many of you in one of these chats. Thanks again to Preeti Malani, and the folks at JAMA for supporting us - both with providing a toll-free access to the article (at this link), and for providing some prizes - cool JAMA swag! 

So for discussion, the topics will be

  • T0: Do you use a risk score to stratify patients pre-op for risk of AKI? The authors in this study used the Cleveland Clinic risk score, but there are others. If you use a risk score, which one do you use?
  • T1: Do you agree with the inclusion exclusion criteria? especially GFR < 30 as an exclusion? How about the particulars of doing the RIPC? 50 mm Hg > systolic or 200 mm Hg, whichever is lower for 5 minutes X 3. Is the sham acceptable? Lack of blinding the investigators an issue?
  • T2: Dive into the results. What do people make of the difference in secondary outcomes (less effect in mild AKI?). The biomarker outcomes are also intriguing, do you agree with the interpretation?
  • T3: What happens now? The authors think of this as a phase-2 study. What outcomes would you like to see in the next study? Intervention is simple and cheap - or is it? 

Cleveland Clinic Foundation score? What's up with that?

This week's NephJC is discussing JAMA's provocative paper on reversible ischemic preconditioning. The methods used The Cleveland Clinic Foundation ARF score to enroll high risk patients:

I had heard of this but was not facile with it. Some quick googling pulled up this Paganini paper about the derivation and validation of the score:

Here is the score they used to predict the risk of dialysis requiring acute renal failure after cardiac surgery:

Look at the score from a creatinine of just 2.1 mg/dl!

Here is the risk from the scores:

Those confidence intervals for scores above 9 are scary wide, but it looks pretty reliable below there.

This Cleveland Clinic Foundation Score was at the center of an interesting Twitter interaction last week. 

Here is the table in question with the strange Cleveland Clinic Score highlighted:

Ross got a quick response from the editors of JAMA. Color me impressed:

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#NephJC does #pericytes: part 2

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Part 2 continued to be epic - with first author Rafael Kramann joining in this time. Check out the storify from Hector below -

And the stats were equally impressive - overall picture captured by this tweet from Matt:

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#NephJC does #pericytes - part 1

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Not #parasites or ... #pedicure?

This was a fantastic chat last night, with great questions from Mal Parmar, Scott Brimble, Dylan Burger and others; clear and articulate answers from Ben Humphreys - and a link heavy tweeting from Matt Sparks. The transcript will read almost like a review article - or commentary.

Stay Tuned for the EU/African chat, occurring in just over 2 hours at 8 pm *BST* - with first author Rafael Kramann joinin in this time.

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In the Literature...

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We mentioned the #MICE project in the newsletter a few days ago (what newsletter?? Check out and sign up - low volume, once a week, will keep you updated) - authored by Tejas Desai, Edgar Lerma, Ryan Madanick et al. It's published on the Winnower platform and has already accumulated some interesting reviews, including Chi Chu & Francesco. Two in particular stand out for their insightful comments - out-rivalling any peer review you may have seen, by Len Starnes and David Goldfarb, the latter written in his incomparable signature style.

Another fun paper (CoI alert: includes Swapnil and Joel as co-authors) is a 'Ten Steps for Setting up an Online Journal Club' - available here ($walled). This was a fun experience - crowd-sourced, written from start to end in a matter of days, and shepherded quite ably by Teresa Chan to publication. 

Being Mortal: Chapter Seven

I did not like the Immortal Life of Henrietta Lacks. I thought the story of the HeLa cells and the story of Ms Lacks and her family was interesting and introduced me to a history of medicine that had previously been invisible. The story was fascinating but the book fell flat because of the way that the author, Rebecca Skloot, inserted herself into the story. Every chapter that was told from Ms. Skloot's point of view came across as having low stakes and was generally uninteresting. I finished the book with the belief that this point-of-view writing was a poor technique for non-fiction.

I was wrong. While it didn't work for the Immortal Life, Dr. Gawande uses it to dramatic effect in Being Mortal. Gawande is a recuring character in the book and the previous chapters we are taken on his journey from a doctor with conventional western medicine understanding about dying o a much deeper and richer understanding. In chapter seven, however, Gawande changes from a researcher to an active participant as his dad suffers a devastating illness and he needs to put his new found knowledge of hospice, assisted living, palliative care and end-of-life decisions to use.

“The scan revealed a tumor growing inside his spinal cord.
That was the moment when we stepped through the looking glass. Nothing about my father’s life and expectations for it would remain the same. Our family was embarking on its own confrontation with the reality of mortality. The test for us as parents and children would be whether we could make the path go any differently for my dad than I, as a doctor, had made it go for my patients. The No. 2 pencils had been handed out. The timer had been started. But we had not even registered that the test had begun.”

In 2006, Gawande's father, Dr. Atmaram Gawande, went for an MRI to diagnose a slowly progressive pain in his neck associated with numbness in his left hand. The scan revealed a spinal cord tumor.

The Gawande's then consulted a pair of neurosurgeons, one in Boston and one at the Cleveland Clinic. Gawande explains the bedside manner of both doctors by describing a paper by the medical ethicists Linda and Ezekiel Emmanuel that described the three type of relationships doctors could have with patients:

  1. Paternalistic
  2. Informative
  3. Interpretive

Gawande describes all three types. The first is the doctor we read about from the 50's. The all knowing God-like figure that tells the patients what they should do and does not discuss options that the doctor does not think are optimal. We would like to think that we are past this but in reality it is more common than we care to admit. 

The second type, informative, is the opposite of the paternalistic relationship. The doctor informs the patient of the facts and figures needed to figure out the best option and then lets the patient make the decision. Gawked explains that this works best for for simple issues with clear choices and straightforward trade-offs. The more complex and emotional the issue the more this method breaks down.

The Emmanuels third option, interpretive, is a hybrid of the two earlier models. “Here the doctor’s role is to help patients determine what they want. Interpretive doctors ask, “What is most important to you? What are your worries?” Then, when they know your answers, they tell you about the red pill and the blue pill and which one would most help you achieve your priorities.”

The chapter winds its way through his father's illness and we see Gawande struggle to use the lessons he has learned to help his father. They make some excellent decisions, they make some mistakes, they meet some excellent physicians and some clunkers. The face decisions on hospice, medical decision making and hospice. Despite some missteps, by the end of the chapter his father is in hospice and living a surprisingly full life.

“But walking slowly, his feet shuffling, he went the length of a basketball floor and then up a flight of twenty concrete steps to join the families in the stands. I was almost overcome just witnessing it. Here is what a different kind of care—a different kind of medicine—makes possible, I thought to myself. Here is what having a hard conversation can do.”


Being Mortal: Chapter Six

Hector Madariaga, NSMC intern and transplant fellow wrote the summary for this chapter.

Chapter Six: Letting Go

Most of this chapter describes the sad case of Sara Thomas Monopoli and her journey from being diagnosed with metastatic lung cancer while 39 weeks pregnant with her first child to her demise a few months later. She was only 34 years old. Sarah failed multiple rounds of chemotherapy and despite continually deteriorating, she, nor her family, came to terms with her impending death and she passed in the ICU without saying goodbye.

Dr Gawande discusses the fact that 25% of all Medicare spending is for the 5% of patients in their final year of life, and most of that money is spent in the final few months. He describes the finances of breast cancer where $28,000 is spent in the first year, primarily on surgery, radiation and chemotherapy. After that the costs fall to $2,000 per year until the final year of fatal cases of where the costs swell to $94,000. (ref)

“Our medical system is excellent at trying to stave off death with $12,000-a-month chemotherapy, $4,000-a-day intensive care, $7,000-an-hour surgery. But, ultimately, death comes, and few are good at knowing when to stop.”
— Atul Gawande

This intense medicalization of death arguably does more harm than good. A study in 2008 showed that cancer patients who were put on a ventilator, given defibrillation, chest compressions, or admitted to an ICU had a substatnitally worse quality of life in their last week of life. Worse, is that this trauma is passed on to loved ones. Caregivers of these patients had three times the rate of major depression. (JAMA 2008)

He describes how advancements in medicine make death a long process rather than an event that lasts a few hours to days. He describes ars moriendi, literally the art of dying. These were prescribed customs people followed when they died. These procedures were published in popular pamphlets and described seeking forgiveness from God, letting go of worldly possessions, and provided friends and families prayers and guidance for the final hours. Gawande argues that we need a new ars moriendi appropriate for the contemporary reality of the end of life.

“So I sat with her sisters in the ICU’s family room to talk about whether we should proceed with the amputation and the tracheostomy.
“Is she dying?” one of the sisters asked me.
I didn’t know how to answer the question. I wasn’t even sure what the word “dying” meant anymore. In the past few decades, medical science has rendered obsolete centuries of experience, tradition, and language about our mortality and created a new difficulty for mankind: how to die.”
— Atul Gawande

e also describes his rounding with Sarah Creed, a nurse practitioner on the hospice service. He interviews the patients and explores their decision to go into hospice care.  One
thing that I learned is that hospice care is not about “letting nature take its course” or to prolong life (that’s the goal of medicine), but to focus on patients' priorities. Their first patient had end-stage heart failure with pulmonary fibrosis. Sarah helped her get medication refills which had been sitting at the pharmacy.

He also explores the rational of terminal patients when they are given a poor prognosis and why they continue to pursue therapy with the hope of extending their lives, when in fact, they only have months to live. Sarah explains that 99% of her patients understand they are dying but they all still hope that they are not. Only about quarter of them have accepted their fate.

The next patient is Dave Galloway, a former firefighter with pancreatic cancer. He is in terrible pain and Sarah has to convince him to use the PCA pump more often. Gawande goes in to detail about a "comfort pack" which is a bundle of useful medications for everything from dyspnea to delirium. Dave's wife knows how to use the medications and is provided with a 24-hour phone line she can call for advice of what medications to use in which situations. The comfort pack provides her an ability to provide care to her husband through his final days and keep him at home comfortably.

Gawande talks a bit about how difficult a problem this is to solve, since solutions often sound like rationing. He then goes on to discuss the story of Nelene Fox, the women who sued Health Net when they refused to pay for her bone marrow transplant for breast cancer. The insurance company did not pay for the experimental procedure. A jury awarded $89 million to her family. Legislators in 10 states then enacted laws requiring insurance companies to pay for bone marrow transplants. The procedure has since been shown to be ineffective for breast cancer. [Note: Intererested readers should check out The Emperor of All Maladies, a great book that digs into the science behind bone marrow transplant for breast cancer and the scientific fraud that perpetuated this practice.]

A landmark study from MGH is also mentioned, in which they randomized 151 patients with stage IV lung cancer. Half received usual oncology care and the other half oncology care plus visits with a palliative care specialist. The results were fascinating. Those in the second group, stopped chemotherapy sooner, opted for Hospice care earlier and lived 25% longer. A similar study is also mentioned in where they too found that palliative care extends survival. As stated in the text:
“You live longer only when you stop trying to live longer.” 

“If end-of-life discussions were an experimental drug, the FDA would approve it.”

The author also explained the end-of-life discussion in the community of La Crosse, Wisconsin in which their is a systematic and widespread effort to get people to discuss end-of-life wishes prior to the, you know, end-of-life. When ever someone in La Crosse is admitted to a hospital, nursing home or assisted living facility they complete a four question form:

  1. Do you want to be resuscitated if your heart stops?

  2. Do you want aggressive treatments such as intubation and mechanical ventilation?

  3. Do you want antibiotics?

  4. Do you want tube or intravenous feeding if you can’t eat on your own?

They increased advance directives from 15% to 85% in 5 years. The ICU doctor Gawande talked with explained that the benefit is not the answer per se but that people have discussed the issues long before they are admitted to the ICU. End-of-life costs in La Crosse are half the national average.

How to approach the end-of-life discussions? Every case has to be individualized; some general rules are: sit down, take your time to talk to family and patients, learn what’s most important for the patient under any circumstance and finally, listening. As Mrs Block, a Palliative care specialist says: “if you are talking more than half of the time, you’re talking too much.”

Being Mortal: Chapter Five

Francesco Iannuzzella wrote the summary for chapter 5.

Chapter Five: A Better Life

In order to maintain the integrity of their social network, and enjoy a higher quality of life, most elderly people would prefer to remain in their homes as long as possible. Nevertheless, at some time during their life, many of them will be admitted to a nursing home.

Traditionally, nursing homes have been organized to provide an efficient medical care to frail and impaired individuals with little or no attention given to quality of life. Fortunately, the deepest changes usually start on a very small scale and one single successful experience can radically change the way of doing something. 

In the beginning of chapter five, Gawande describes the biography of one of these heroes, Bill Thomas, a man who rewrote the manual on how nursing homes operate.

Bill Thomas’s experience began in the early 1990s when he got a new job as medical director of Chase Memorial Nursing home in the town of New Berlin, NY. He was only thirty-one with little or no experience in eldercare. With his newcomer’s eyes, Bill began to question the basic assumptions all had taken for granted since then.

He identified “The Three Plagues” of nursing home existence:

  1. boredom
  2. loneliness, and
  3. helplessness.

Then, he tried to fix them experimenting a new approach to eldercare. His aims were clear: he wanted to replace boredom with spontaneity, loneliness with companionship, and helplessness with a chance to become involved in caring for another being. At the beginning, he didn’t make a great change in everyday Chase Memorial healthcare practice, but he adopted an easy and effective approach to bring life to its inhabitants: he introduced a lot of pets, gardens and children to the nursing home.

“He said, “Now, what about cats?”
I said, “What about cats?” I said, “We’ve got two dogs down on the paper.”
He said, “Some people aren’t dog lovers. They like cats.”
I said, “You want dogs AND cats?”
He said, “Let’s put it down for discussion purposes.”
I said, “Okay. I’ll put a cat down.”
“No, no, no. We’re two floors. How about two cats on both floors?”
I said, “We want to propose to the health department two dogs and four cats?”
He said, “Yes, just put it down.”
I said, “All right, I’ll put it down. I think we’re getting off base here. This is not going to fly with them.”
He said, “One more thing. What about birds?”
I said that the code says clearly, “No birds allowed in nursing homes.”
He said, “But what about birds?”
I said, “What about birds?”
He said, “Just picture—look out your window right here. Picture that we’re in January or February. We have three feet of snow outside. What sounds do you hear in the nursing home?”
I said, “Well, you hear some residents moaning. You possibly hear some laughter. You hear televisions on in different areas, maybe a little more than we’d like them to be.” I said, “You’ll hear an announcement over the PA system.”
“What other sounds are you hearing?”
I said, “Well, you’re hearing staff interacting with each other and with residents.”
He said, “Yeah, but what are those sounds that are sounds of life—of positive life?”
“You’re talking birdsong.”
“Yes!”
I said, “How many birds are you talking to create this birdsong?”
He said, “Let’s put one hundred.”
“ONE HUNDRED BIRDS? IN THIS PLACE?” I said, “You’ve got to be out of your mind!”

Wilma and Libby

Wilma and Libby

The results were extraordinary:

  • The number of prescriptions halved
  • With a particular reduction in the use of psychotropic drugs
  • Mortality fell about 15%.

This was the starting point for a larger program, named Eden Alternative, which over the last 20-years de-institutionalized nursing homes and ultimately lead to the so-called Green House project. Since the first Green House was built in Tupelo, Mississipi, in the year 2000, more than 150 Green Houses have been built in twenty-five states. With no more than twelve residents each, all Green Houses are small and communal with a physical environment made to preserve quality of life, self-sufficiency, privacy, and dignity.

How to explain the Eden Alternative success?

To answer this question, Gawande cites an American philosopher, Josiah Royce (1855-1916), who believed that in order to live a worth living we need loyalty, i.e. a dedication to a cause beyond ourselves. It doesn’t matter if this cause is small (as small as the care for a pet) or large, what matters is that is such a cause provide meaning to one's life. We all need loyalty, and elderly people need it even more.

“The elderly need loyalty to give meaning to both their life and their death.”

They need loyalty to give meaning to both their life and their death. With aging, simple pleasures,  we all take for granted during our adulthood, may become a source of loyalty, a comfort to our pain. To testify to this truth, Gawande reports the interviews tof nursing home residents he met, whose quality of life strictly depends upon simple pleasures: living in a private room, going to the cinema, reading Fifty Shades of Grey, using a computer, preserving social interactions.

Gawande describes his experience visiting two different projects in the Boston area. The first one, it is a new human size retiring community called NewBridges on the Charles with great financial resources due to substantial philanthropic support.  The second project is a subsidized apartment building (Peter Sanbord Place) for low-income elderly people, whose director Jacquie Carson deeply changed to allow her residents to continue to live their own lives.

The chapter ends by returning to the story of Lou Sanders who has deteriorated to the point where he no longer can live in assisted living and is admitted to a nursing home. However, he enters a Green House with private rooms and a thoroughly de-institutionalized philosophy. He rapidly adapts and explains that he knew it was the place for him when he saw that all the rooms were single. Little things can make all the difference.

 

The President of the ASN (@POTASN) is doing a Twitter chat, #AskASN

Tonight at 9pm Eastern Dr. Himmelfarb will be doing an hour chat.

Hashtag: #askASN.

Topics

Topic Zero- What is your favorite ASN memory?

Topic One: What does ASN mean to you?

Topic One: Why did you want to serve as ASN President?

Topic Two: What is ASN doing for the #NephWorkForce?

Topic Two: Why did the Match Task Force and the Council vote for the "all-in approach" to the Match? What does that mean?

Topic Three: Why are you on Twitter? What are you hoping to accomplish?

Topic Four: How has nephrology changed since you were a fellow?

Topic Four: How old are you? What color was your Burton Rose?

Topic Five: What does the ASN of 2025 look like?

 

Being Mortal: Chapter Four

Swapnil Hiremath summarized chapter four, bringing us to the the halfway point. Remember the chat is next Tuesday and Wednesday, July 14 and 15.

Chapter 4: Assistance

“Life is pleasant. Death is peaceful. It’s the transition that’s troublesome.”
— Isaac Asimov

Atul Gawande continues in Chapter 4 with vignettes of frail elderly individuals facing loss of independence, and the difficult choices they face. This time it is the story of Lou Sanders, a gregarious ex-veteran living in a working class Boston neighbourhood. Lou's comfortable life starts unravelling soon after his wife’s passing. As an aside, it is notable how a ‘tipping point’ often is the death of a partner (and though there have been no stories so far of single/unattached individuals, I suspect they would be doing much worse at this stage). [note to self: buy flowers on the way home tonight]. Being a very social person, Lou is adamant in refusing to move to a nursing home ‘full of old people.’ He even forces his daughter to swear to never ship him off to a nursing home. After a heart attack, followed by Parkinson’s and additional falls, he agrees to move in with his daughter Shelley, an extraordinarily supportive and willing caregiver. The realities of the modern nuclear family however intrude, and this transition is not as smooth – unlike the story of the author’s grandfather Sitaram living in a large joint family. The toll of being a full time working professional, homemaker, and also caregiver for her father’s increasing needs proves to be too much for Shelley. Medical problems include hearing difficulty, prostatism, incontinence and continuing falls. The last is exacerbated with postural hypotension (likely due to the autonomic dysfunction common with Parkinson’s – and/or the drugs used to treat it). Lou continues to refuse moving to a nursing home, and is ultimately and unhappily transitioned into an assisted living facility.

The story of assisted living facilities, and how they came into being is one of the amazing stories that make Being Mortal such a compelling story. It is the story of Keren Brown Wilson, and her stroke-struck mother’s plaintive request to her, ‘Why don’t you do something to help people like me?’ Keren mother's request was a plea for autonomy and respect.

“She wanted a small place with a little kitchen and a bathroom. It would have her favorite things in it, including her cat, her unfinished projects, her Vicks VapoRub, a coffeepot, and cigarettes. There would be people to help her with the things she couldn’t do without help. In the imaginary place, she would be able to lock her door, control her heat, and have her own furniture. No one would make her get up, turn off her favorite soaps, or ruin her clothes. Nor could anyone throw out her “collection” of back issues and magazines and Goodwill treasures because they were a safety hazard. She could have privacy whenever she wanted, and no one could make her get dressed, take her medicine, or go to activities she did not like. She would be Jessie again, a person living in an apartment instead of a patient in a bed.”

So Keren and her husband, both academics, sketched out a plan for a new kind of place, and cleared endless bureaucratic and and financial  hurdles to open ‘Park Place’ in Portland, Oregon. It had many innovative, almost radical, components – one of the most important being that the residents were called ‘tenants’, not patients, and had many more rights – such as a locked front door to their apartments.  Despite this increased freedom, there was no trade-off with worsening safety as feared. The state of Oregon made Wilson track data – and it revealed improved outcomes (including satisfaction) with lower costs. In hindsight, much of this is now unsurprising, if we consider Maslow’s hierarchy of needs.

ource: https://en.wikipedia.org/wiki/Maslow's_hierarchy_of_needs#/media/File:MaslowsHierarchyOfNeeds.svg ; used under Creative Commons license.

Much of the research in this area is done by Laura Carstensen, now a Stanford Professor in Longevity, but once a high school educated almost single mother (read chapter 4 for the truly amazing story of how everything changed for her). Perspectives change as the end of life appears closer on the horizon, and comfort and companionship become valued over other ambitions. Unfortunately, the kind of assisted living started by Keren Brown Wilson has now morphed into something else entirely, with very few facilities including the core concepts from her original vision. The fate of Lou Sanders was in one such place. After initially coping and adjusting, the falls and more critical events force Shelley to ‘place’ him in a nursing home...

“a medically designed answer to unfixable problems, a life designed to be safe but empty of anything they care about.”