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[[Image:Peritoneal_dialysis.gif|thumb|250px|Peritoneal dialysis]]
 
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[[Image:Peritoneal_dialysis.gif|thumb|250px|Peritoneal dialysis Source:National Kidney and Urologic Diseases Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA, via wikimedia commons<ref>https://commons.wikimedia.org/wiki/File:Peritoneal_dialysis.gif</ref>]]
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==Overview==
==Overview==
'''Peritoneal dialysis''' is a method for removing waste such as [[urea]] and [[potassium]] from the [[blood]], as well as excess fluid, when the [[kidney]]s are incapable of this (i.e. in [[renal failure]]). It is a form of [[dialysis|renal dialysis]], and is thus a [[renal replacement therapy]].
Peritonial [[dialysis]] is a procedure to remove waste and excess fluid e.g. [[urea]] and [[potassium]] from blood when [[Kidney|kidneys]] are no longer capable of doing so, such as in cases of [[renal failure]]. Peritonial [[dialysis]] is a type of [[Dialysis|renal dialysis]] and therefore also referred to as [[renal replacement therapy]]. It follows the process of [[diffusion]], wherein [[peritoneal]] [[membrane]] surrounding the [[Viscera|abdominal viscera]] serves a [[semipermeable membrane]] and can, in the presence of specifically formulated dialysis [[fluid]], help [[dialysis]]. Another process involves [[osmosis]] wherein excessive [[fluid]] can be removed by altering the concentration of [[glucose]] in the [[dialysis]] [[fluid]]. The [[fluid]] used for [[dialysis]] is instilled via a [[catheter]]. The most common dialysis catheter is Tenckhoff [[Catheter]]. It is placed in the patient's [[peritoneum]] and runs to the skin surface near the [[umbilicus]]. These [[Catheter|catheters]] may also be tunneled subcutaneously and exit various locations such as near the [[rib]] margin or close to [[sternum]] (presternal [[catheter]]) or even higher  near the [[clavicle]]. The [[procedure]] involves a small [[surgery]] and choice of exit site is influenced by multiple factors viz patient's or surgeon's preference, [[anatomical]] variations, and/or ability to maintain good [[hygiene]]. [[Peritoneal]] [[dialysis]] can be done anywhere; at home or at workplace and all it requires is a clean area, a way to elevate the fluid bag, and means to warm the fluid. As one may imagine, there is, however, a predilection for infection e.g. [[peritonitis]]. Hence the importance of taking hygienic precautions cannot be over emphasized.
 
Peritoneal dialysis works on the principle that the peritoneal membrane that surrounds the [[intestine]], can act as a natural semipermeable membrane (see [[dialysis]]), and that if a specially formulated dialysis fluid is instilled around the membrane then [[dialysis]] can occur, by [[diffusion]]. Excess fluid can also be removed by [[osmosis]], by altering the [[concentration]] of [[glucose]] in the fluid.


Dialysis fluid is instilled via a peritoneal dialysis [[catheter]], (the most common type is called a '''Tenckhoff Catheter''') which is placed in the patient's abdomen, running from the peritoneum out to the surface, near the [[navel]]. Peritoneal dialysis catheters may also be tunneled under the skin and exit alternate locations such as near the rib margin or sternum (called a presternal catheter), or even up near the clavicle.  This is done as a short surgery.  The exit site is chosen based on surgeon's or patient's preference and can be influenced by anatomy or hygiene issues.
==Types ==
 
Peritoneal dialysis is typically done in the patient's home and workplace, but can be done almost anywhere; a clean area to work, a way to elevate the bag of dialysis fluid and a method of warming the fluid are all that is needed. The main consideration is the  potential for [[infection]]. [[Peritonitis]] is the most common serious complication, but with good technique can usually be avoided. Infections of the catheter's exit site or "tunnel" (path from the [[peritoneum]] to the exit site) are less serious. Because of this, patients are advised to take a number of precautions against infection.
 
==Methods ==
There are three types of peritoneal dialysis: <ref name="pmid14582053">{{cite journal |vauthors=Teitelbaum I, Burkart J |title=Peritoneal dialysis |journal=Am. J. Kidney Dis. |volume=42 |issue=5 |pages=1082–96 |date=November 2003 |pmid=14582053 |doi= |url=}}</ref><ref name="pmid25587214">{{cite journal |vauthors=Hauch AT, Lundberg PW, Paramesh AS |title=Laparoscopic techniques enable peritoneal dialysis in the difficult abdomen |journal=JSLS |volume=18 |issue=4 |pages= |date=2014 |pmid=25587214 |pmc=4283101 |doi=10.4293/JSLS.2014.002334 |url=}}</ref>  
There are three types of peritoneal dialysis: <ref name="pmid14582053">{{cite journal |vauthors=Teitelbaum I, Burkart J |title=Peritoneal dialysis |journal=Am. J. Kidney Dis. |volume=42 |issue=5 |pages=1082–96 |date=November 2003 |pmid=14582053 |doi= |url=}}</ref><ref name="pmid25587214">{{cite journal |vauthors=Hauch AT, Lundberg PW, Paramesh AS |title=Laparoscopic techniques enable peritoneal dialysis in the difficult abdomen |journal=JSLS |volume=18 |issue=4 |pages= |date=2014 |pmid=25587214 |pmc=4283101 |doi=10.4293/JSLS.2014.002334 |url=}}</ref>  
* '''Continuous ambulatory peritoneal dialysis''' ('''CAPD'''), the most common type, needs no machine and can be done at home. Exchanges of fluid are done throughout the day, usually four exchanges a day.<ref name="pmid16813998">{{cite journal |vauthors= |title=Clinical practice guidelines for peritoneal dialysis adequacy |journal=Am. J. Kidney Dis. |volume=48 Suppl 1 |issue= |pages=S98–129 |date=July 2006 |pmid=16813998 |doi=10.1053/j.ajkd.2006.04.006 |url=}}</ref>  
* '''Continuous ambulatory peritoneal dialysis''' ('''CAPD'''), the most common type, needs no machine and can be done at home. Exchanges of fluid are done throughout the day, usually four exchanges a day.<ref name="pmid16813998">{{cite journal |vauthors= |title=Clinical practice guidelines for peritoneal dialysis adequacy |journal=Am. J. Kidney Dis. |volume=48 Suppl 1 |issue= |pages=S98–129 |date=July 2006 |pmid=16813998 |doi=10.1053/j.ajkd.2006.04.006 |url=}}</ref>  
* '''Continuous cyclic peritoneal dialysis''' ('''CCPD''') uses a machine and is usually performed at night when the person is sleeping.<ref name="pmid16813998" /><ref name="pmid14582053" />  
* '''Continuous cyclic peritoneal dialysis''' ('''CCPD''') uses a machine and is usually performed at night when the person is sleeping.<ref name="pmid14582053" /><ref name="pmid16813998" />  
* '''Intermittent peritoneal dialysis''' ('''IPD''') uses the same type of machine as CCPD - if done overnight is called Nocturnal intermittent peritoneal dialysis (NIPD)<ref name="pmid14582053" />.
* '''Intermittent peritoneal dialysis''' ('''IPD''') uses the same type of machine as CCPD - if done overnight is called Nocturnal intermittent peritoneal dialysis (NIPD)<ref name="pmid14582053" />.
== Indications ==
Indications of peritoneal dialysis include:
*[[Uremia]]<ref name="pmid264984152">{{cite journal |vauthors=Slinin Y, Greer N, Ishani A, MacDonald R, Olson C, Rutks I, Wilt TJ |title=Timing of dialysis initiation, duration and frequency of hemodialysis sessions, and membrane flux: a systematic review for a KDOQI clinical practice guideline |journal=Am. J. Kidney Dis. |volume=66 |issue=5 |pages=823–36 |date=November 2015 |pmid=26498415 |doi=10.1053/j.ajkd.2014.11.031 |url=}}</ref>
*[[Metabolic]] derangements
*[[Heart failure]]
For details on indications of dialysis [[Dialysis#Indications|click here]]


==Advantages and disadvantages of Peritoneal dialysis==
==Advantages and disadvantages of Peritoneal dialysis==
===Advantages<ref name="pmid14582053" />===
===Advantages===
The following are the advantages:<ref name="pmid16813998" /><ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE3">{{cite web |url=http://www.pdiconnect.com/content/30/4/393.short |title=PERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE |format= |work= |accessdate=}}</ref>
The following are the advantages:<ref name="pmid14582053" /><ref name="pmid16813998" /><ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE3">{{cite web |url=http://www.pdiconnect.com/content/30/4/393.short |title=PERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE |format= |work= |accessdate=}}</ref>
* Can be done at home.
* Can be done at home.
* Relatively easy to learn.   
* Relatively easy to learn.   
* Easy to travel with, bags of solution are easy to take on holiday.
* Easy to travel with, bags of solution are easy to take on holiday.
* Fluid balance is usually easier than on hemodialysis
* Theoretically better to start dialysis on, as native urine output is maintained for longer than on hemodialysis.<ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE3" />
* Excluding kidney transplant, PD is method of the first choice in treating chronic kidney failure.


===Disadvantages===
===Disadvantages===
Line 34: Line 34:


==Complications==
==Complications==
Following are the complications associated with Peritoneal Dialysis:<ref name="pmid16813998" /><ref name="pmid14582053" />
Following are the complications associated with Peritoneal Dialysis:<ref name="pmid14582053">{{cite journal |vauthors=Teitelbaum I, Burkart J |title=Peritoneal dialysis |journal=Am. J. Kidney Dis. |volume=42 |issue=5 |pages=1082–96 |date=November 2003 |pmid=14582053 |doi= |url=}}</ref><ref name="pmid16813998" />
* [[infection]]<ref name="pmid16813998" /><ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE" />
* [[Infection]]<ref name="pmid16813998" />
* [[peritonitis]]<ref name="pmid16813998" /><ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE" /><ref name="urlacademic.oup.com">{{cite web |url=https://academic.oup.com/ndt/article/11/3/498/1839969 |title=academic.oup.com |format= |work= |accessdate=}}</ref>
* [[Peritonitis]]<ref name="pmid16813998" /><ref name="urlacademic.oup.com">{{cite web |url=https://academic.oup.com/ndt/article/11/3/498/1839969 |title=academic.oup.com |format= |work= |accessdate=}}</ref>
* [[Hernias]]  
* [[Hernias]]  
* Accumulation of [[fibrin]] in the PD effluent<ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE3" />  
* Accumulation of [[fibrin]] in the PD effluent<ref name="urlPERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE3" />  
* Damage to [[Peritoneal membrane.|peritoneal membrane]]
* Damage to peritoneal membrane
* [[Diabetes]] because of the [[glucose]] levels that are in the 'bags'
* [[Diabetes]] because of the [[glucose]] levels that are in the 'bags'
* [[Fluid]] leaks into surrounding [[soft tissue]], often the [[scrotum]] in males
* [[Fluid]] leaks into surrounding [[soft tissue]], often the [[scrotum]] in males


==Step-by-step description of Peritoneal dialysis (a CAPD exchange)==
==CAPD exchange==
#The supplies and materials needed for an exchange are...VEXORG THE DEVOURER OF CHICKENS and STUFF. Notable amongst these is a bag of dialysis fluid (also called dialysis solution), a solution comprised of a known amount of a [[glucose]] dissolved in water.<ref name="pmid14582053" /><ref name="pmid16813998" /> The strength of this solution determines the osmotic gradient, and therefore the amount of water that diffuses out of the bloodstream. Common strengths of glucose are 0.5%, 1.5%, 2.5% and 4.25%. 1.5% is approximately fluid-neutral; it neither adds nor removes fluid and is used for patients who are primarily concerned with waste removal rather than fluid regulation. Higher concentrations lead to greater water removal. A higher dextrose concentration moves fluid and more wastes into the abdominal cavity, increasing both early and long-dwell exchange efficiency. Eventually, however, the body absorbs dextrose from the solution.<ref name="pmid14582053" /><ref name="pmid16813998" /> As the concentration of dextrose in the body comes closer to that in the solution, dialysis becomes less effective, and fluid is slowly absorbed from the abdominal cavity. [[Electrolytes]] are also present in the fluid to maintain proper body levels. Patients weigh themselves, and measure temperature and blood pressure daily to determine whether the body is retaining fluid and, thus, what strength of fluid to use. Dialysis fluid typically comes premixed in a disposable bag-and-tube apparatus; no additional equipment is needed.<ref name="pmid14582053" /> <ref name="urlPeritoneal Dialysis and the Process of Modality Selection">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649891/ |title=Peritoneal Dialysis and the Process of Modality Selection |format= |work= |accessdate=}}</ref>The apparatus consists of two bags, one empty and one with the fluid, connected via flexible tubing to a Y-shaped fitting. The bag is heated to body temperature, to avoid causing cramping. Dry heat is used; common methods include [[microwave oven|microwaves]] (microwave heating is NOT recommended), [[heating pad]]s and [[solar radiation]] (often using the dashboard of a car, for instance while travelling).
===Precautions:===
#The patient, who performs the entire procedure themselves, dons a disposable [[surgical mask]], scrubs their hands using [[antibacterial]] soap, and tucks a clean towel into the waistband of their pants to protect their clothing. The bag of dialysis fluid is removed from the protective packaging, and is hung from an [[intravenous|IV]] stand or other elevated location, such as a coat hook. The tubing attached to the bag of fluid is uncoiled, and the second (empty) bag is placed on the floor. The Y-shaped connector is attached to the catheter tip; a protective cap must be removed from both of these before the connection is made, and the two portions of the connector are not permitted to touch anything, to avoid possible contamination.<ref name="pmid16813998" /><ref name="pmid14582053" />
* A disposable [[surgical mask]]
#Once connected to the system, the patient clamps the tubing connected to the full bag of dialysis fluid and then releases the twist valve located in the tip of their catheter; this permits fluid to flow into or out of the peritoneal cavity. Because the full bag of fluid is clamped off but the empty bag is not, the effluent (used dialysis fluid) from within the peritoneum can drain out of the catheter and into the lower, waste bag. Emptying the abdomen of fluid takes approximately fifteen minutes, and the patient is free to perform tasks such as reading, watching television and browsing the internet.<ref name="pmid16813998" />
* [[Antibacterial]] soap
#When the abdomen has drained, the lower drain-bag is clamped off. The twist valve in the catheter is also closed. The clamp is then removed from the upper tubing, permitting dialysis fluid to drain out into the abdomen. The clamp to the drain bag is briefly opened and some fluid is drained directly from the upper bag into the lower bag. This clears the line of air and other impurities. The drain line is then clamped off and the twist valve on the catheter end is opened. This permits fluid to enter the peritoneum. Filling the abdomen with fresh fluid takes about fifteen minutes, and the patient enjoys the same freedoms as while draining.
* [[Intravenous|IV]] stand or other elevated location, such as a coat hook.<ref name="pmid14582053" /><ref name="pmid16813998" />
#Once the entire bag of fluid (an amount varying primarily based on body size, ranging from 1500 to 3000 [[milliliter|mL]]) has been introduced to the abdomen, the patient then cleans their hands again (typically using an [[antiseptic]] alcohol-based cleanser) and puts the surgical mask on. The Y-connector is detached from the catheter tip and a protective cap is placed on the end of the catheter.<ref name="pmid14582053" />
 
#The effluent is inspected after a dialysis exchange is complete; a cloudy effluent indicates probable peritoneal infection. The effluent is drained into a toilet, and the various dialysis supplies are discarded with normal garbage.
====Materials needed:====
* A dialysis fluid bag: contains [[glucose]] and [[Electrolyte|electrolytes]] dissolved in water.<ref name="pmid14582053" /><ref name="pmid16813998" />  
* Two bags: one empty and one with the [[fluid]], connected via flexible tubing to a [[Y-shaped fitting]].
 
===== Process: =====
* Once connected to the [[system]], the patient clamps the tubing connected to the full bag of dialysis fluid and then releases the twist valve located in the tip of their catheter; this permits fluid to flow into or out of the [[peritoneal cavity]]. Because the full bag of fluid is clamped off but the empty bag is not, the effluent (used [[dialysis fluid)]] from within the [[peritoneum]] can drain out of the [[catheter]] and into the lower, waste bag. Emptying the [[abdomen]] of fluid takes approximately fifteen minutes.<ref name="pmid16813998" />
{| align="center"
|
{{#ev:youtube|qKAA4tpr0pU}}
|}
*When the [[abdomen]] has drained, the lower drain-bag is clamped off. The twist valve in the [[catheter]] is also closed. The clamp is then removed from the upper tubing, permitting [[dialysis]] fluid to drain out into the abdomen. The clamp to the drain bag is briefly opened and some fluid is drained directly from the upper bag into the lower bag. This clears the line of air and other [[impurities]]. The drain line is then clamped off and the twist valve on the [[catheter]] end is opened. This permits fluid to enter the [[peritoneum]]. Filling the [[abdomen]] with fresh fluid takes about fifteen minutes, and the patient enjoys the same freedoms as while draining.<ref name="pmid16813998" />
*Once the entire bag of fluid (an amount varying primarily based on [[Body size scaling|body size]], ranging from 1500 to 3000 [[milliliter|mL]]) has been introduced to the abdomen, the patient then cleans their hands again (typically using an [[antiseptic]] alcohol-based cleanser) and puts the surgical mask on. The Y-connector is detached from the [[catheter]] tip and a protective cap is placed on the end of the catheter.<ref name="pmid14582053" />
*The effluent is inspected after a [[dialysis]] exchange is complete; a cloudy effluent indicates probable [[peritoneal]] [[infection]]. The effluent is drained into a toilet, and the various dialysis supplies are discarded with normal garbage.


==See also==
==See also==
Line 57: Line 69:
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Renal dialysis]]
[[Category:Renal dialysis]]
[[Category:Nephrology]]
[[Category:Nephrology]]
[[es:Diálisis peritoneal]]
[[es:Diálisis peritoneal]]
[[pt: Diálise peritoneal]]
[[pt: Diálise peritoneal]]

Latest revision as of 19:21, 6 August 2018


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]

Peritoneal dialysis Source:National Kidney and Urologic Diseases Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA, via wikimedia commons[1]

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Overview

Peritonial dialysis is a procedure to remove waste and excess fluid e.g. urea and potassium from blood when kidneys are no longer capable of doing so, such as in cases of renal failure. Peritonial dialysis is a type of renal dialysis and therefore also referred to as renal replacement therapy. It follows the process of diffusion, wherein peritoneal membrane surrounding the abdominal viscera serves a semipermeable membrane and can, in the presence of specifically formulated dialysis fluid, help dialysis. Another process involves osmosis wherein excessive fluid can be removed by altering the concentration of glucose in the dialysis fluid. The fluid used for dialysis is instilled via a catheter. The most common dialysis catheter is Tenckhoff Catheter. It is placed in the patient's peritoneum and runs to the skin surface near the umbilicus. These catheters may also be tunneled subcutaneously and exit various locations such as near the rib margin or close to sternum (presternal catheter) or even higher  near the clavicle. The procedure involves a small surgery and choice of exit site is influenced by multiple factors viz patient's or surgeon's preference, anatomical variations, and/or ability to maintain good hygiene. Peritoneal dialysis can be done anywhere; at home or at workplace and all it requires is a clean area, a way to elevate the fluid bag, and means to warm the fluid. As one may imagine, there is, however, a predilection for infection e.g. peritonitis. Hence the importance of taking hygienic precautions cannot be over emphasized.

Types

There are three types of peritoneal dialysis: [2][3]

  • Continuous ambulatory peritoneal dialysis (CAPD), the most common type, needs no machine and can be done at home. Exchanges of fluid are done throughout the day, usually four exchanges a day.[4]
  • Continuous cyclic peritoneal dialysis (CCPD) uses a machine and is usually performed at night when the person is sleeping.[2][4]
  • Intermittent peritoneal dialysis (IPD) uses the same type of machine as CCPD - if done overnight is called Nocturnal intermittent peritoneal dialysis (NIPD)[2].

Indications

Indications of peritoneal dialysis include:

For details on indications of dialysis click here

Advantages and disadvantages of Peritoneal dialysis

Advantages

The following are the advantages:[2][4][6]

  • Can be done at home.
  • Relatively easy to learn.
  • Easy to travel with, bags of solution are easy to take on holiday.

Disadvantages

  • Requires a degree of motivation and attention to cleanliness while performing exchanges.
  • Possible complications (see below)

Complications

Following are the complications associated with Peritoneal Dialysis:[2][4]

CAPD exchange

Precautions:

Materials needed:

Process:
  • Once connected to the system, the patient clamps the tubing connected to the full bag of dialysis fluid and then releases the twist valve located in the tip of their catheter; this permits fluid to flow into or out of the peritoneal cavity. Because the full bag of fluid is clamped off but the empty bag is not, the effluent (used dialysis fluid) from within the peritoneum can drain out of the catheter and into the lower, waste bag. Emptying the abdomen of fluid takes approximately fifteen minutes.[4]

{{#ev:youtube|qKAA4tpr0pU}}

  • When the abdomen has drained, the lower drain-bag is clamped off. The twist valve in the catheter is also closed. The clamp is then removed from the upper tubing, permitting dialysis fluid to drain out into the abdomen. The clamp to the drain bag is briefly opened and some fluid is drained directly from the upper bag into the lower bag. This clears the line of air and other impurities. The drain line is then clamped off and the twist valve on the catheter end is opened. This permits fluid to enter the peritoneum. Filling the abdomen with fresh fluid takes about fifteen minutes, and the patient enjoys the same freedoms as while draining.[4]
  • Once the entire bag of fluid (an amount varying primarily based on body size, ranging from 1500 to 3000 mL) has been introduced to the abdomen, the patient then cleans their hands again (typically using an antiseptic alcohol-based cleanser) and puts the surgical mask on. The Y-connector is detached from the catheter tip and a protective cap is placed on the end of the catheter.[2]
  • The effluent is inspected after a dialysis exchange is complete; a cloudy effluent indicates probable peritoneal infection. The effluent is drained into a toilet, and the various dialysis supplies are discarded with normal garbage.

See also

References

  1. ↑ https://commons.wikimedia.org/wiki/File:Peritoneal_dialysis.gif
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Teitelbaum I, Burkart J (November 2003). "Peritoneal dialysis". Am. J. Kidney Dis. 42 (5): 1082–96. PMID 14582053.
  3. ↑ Hauch AT, Lundberg PW, Paramesh AS (2014). "Laparoscopic techniques enable peritoneal dialysis in the difficult abdomen". JSLS. 18 (4). doi:10.4293/JSLS.2014.002334. PMC 4283101. PMID 25587214.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 "Clinical practice guidelines for peritoneal dialysis adequacy". Am. J. Kidney Dis. 48 Suppl 1: S98–129. July 2006. doi:10.1053/j.ajkd.2006.04.006. PMID 16813998.
  5. ↑ Slinin Y, Greer N, Ishani A, MacDonald R, Olson C, Rutks I, Wilt TJ (November 2015). "Timing of dialysis initiation, duration and frequency of hemodialysis sessions, and membrane flux: a systematic review for a KDOQI clinical practice guideline". Am. J. Kidney Dis. 66 (5): 823–36. doi:10.1053/j.ajkd.2014.11.031. PMID 26498415.
  6. ↑ "academic.oup.com".
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