The Netherlands
The Netherlands (Nederland)
Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients (DOMESTICO)
"La naranja mecánica", "The Dutch Eleven", "Oranje" and "The Orange Legion"...The Dutch field a team that has never been short on big-name figures in the history of football. A small country that has given its fans and supporters a stellar roster of players for whom to cheer. The names are as big as Johan Cruyff (whose legacy would deserve an entire book) and Robin van Persie, who continues to amaze both old and new fans (Video 1).
This year the Dutch enter the NephroWorldCup with an important concept in clinical medicine: Polypharmacy. In the article: Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients (DOMESTICO), researchers present a multi-center cohort study of dialysis patients with a dialysis vintage of 3 months or greater. Using the electronic medical record they accounted for the number of medications these patients were prescribed. The primary endpoint included a number of health-related quality of life metrics measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS). Both PCS and MCS are part of the Short form 12 (SF-12) questionnaire: a validated self-reported questionnaire for dialysis patients (Figure 1). A key secondary endpoint was the frequency of different symptoms measured with the EuroQol-5D-5L (sample copy here).
Video 1: The magic that is Johan Cruyff
Figure 1: SF-12 that contains the PCS and MCS (zoom in for details)
The study is a relevant one. The Netherlands place a strong spotlight, rightfully so, on patient-oriented results (also known as patient-reported outcomes or PRO) (Box 1). PRO is a topic that is gaining more traction within the research and clinical communities around the globe (Figure 2). Does this paper herald the start of a "golden era" for patient-reported outcomes?
Carousel 1: Endpoint models for designing trials that measure PRO | Courtesy of the US Food and Drug Administration | Courtesy Dr. Jennifer Flythe and Dr. Talia Gutman | (zoom in for details)
Figure 2: The importance of PRO | Courtesy of the 2019 Canadian Society of Nephrology Annual General Meeting | (zoom in for details)
Box 1: Definition of PRO. Any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else | Courtesy US Food and Drug Administration
The Oranje is familiar with golden eras! Back in the 70's the Netherlands added a sliver of gold to their familiar orange with stellar on-pitch play. The Dutch fielded such a well-balanced and talented football unit that the favorites, Brazil, lauded them as the only other team capable of greatness! And the Oranje repeated that glory from in the late 90's when greats like Marc Overmars, Phillip Cocu, and the siblings Frank and Ronald de Boer reached the semifinals of 1998 World Cup (only to lose against...you guessed it....Brazil). Their fortunes, however, have come under hard times as they have now earned the dubious distinction of becoming only the second nation to have topped the FIFA rankings and not secured the World Cup.
This year, The Netherlands hopes to pull a "Cruyff turn" and capture more golden attention for both patient-related outcomes (PRO) research and their football team. DOMESTICO included 162 participants who reported a mean number of medications of 12.2 and mean PCS and MCS scores of 36.6 and 46.8 respectively. Let's stop for a minute and take stock of this observation: a mean of 12.2 ± 4.5 medications for all dialysis patients studied in DOMESTICO. If you define "polypharmacy" as taking 5 of more medications at a time, then 98% of all patients in DOMESTICO were experiencing polypharmacy. Holy @#$%^&!
Scoring of the PCS and MCS ranges from 0 to 100. Healthier patients have higher scores. The accepted threshold for a "low" PCS is a score < 50; for the MCS a score < 42 (suggestive of clinical depression) (Figure 3).
After adjustments researchers saw that the addition of one medication would lower the PCS by 0.6 points (95% CI -0.9 to -0.2; p = 0.002). Things on the MCS side are worse; one additional medication reduced the MCS by 4.9 points (95% CI -8.8 to -1.0; p = 0.01). Polypharmacy truly has a negative impact on the physical and mental health of dialysis patients (Video 2). And that negative impact goes far beyond the annoyance or burden of medication non-adherence. Talk about the law of diminishing marginal returns!
Figure 3: Summary of the PCS and MCS scores in the SF-12 | Courtesy https://hqlo.biomedcentral.com/articles/10.1186/s12955-021-01794-w
Controlling patient symptoms is one of the major challenges in managing chronic kidney disease. Physicians have the good intention of alleviating those symptoms with therapeutic agents, but there is a point of diminishing returns (i.e., when the number of meds we prescribe to help patients actually makes their mental and physical health worse through no reason other than the number of pills). Perhaps the real "Cruyff turn" is our acknowledgement that polypharmacy is its own adverse effect separate from pathophysiologically-mediated ones.
Video 2: Polypharmacy: a conversation | Courtesy of Drs. Marisa Battistella and Rasheeda Hall